Glycogen storage disease type I pathophysiology: Difference between revisions
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==Pathophysiology== | ==Pathophysiology== | ||
*GSD | *Glycogen storage disease type 1 (GSD 1) results due to defects in either [[hydrolysis]] or transport of [[glucose-6-phosphate]].<ref name="pmid12373565">{{cite journal| author=Moses SW| title=Historical highlights and unsolved problems in glycogen storage disease type 1. | journal=Eur J Pediatr | year= 2002 | volume= 161 Suppl 1 | issue= | pages= S2-9 | pmid=12373565 | doi=10.1007/s00431-002-0997-6 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12373565 }} </ref><ref name="KishnaniAustin2014">{{cite journal|last1=Kishnani|first1=Priya S.|last2=Austin|first2=Stephanie L.|last3=Abdenur|first3=Jose E.|last4=Arn|first4=Pamela|last5=Bali|first5=Deeksha S.|last6=Boney|first6=Anne|last7=Chung|first7=Wendy K.|last8=Dagli|first8=Aditi I.|last9=Dale|first9=David|last10=Koeberl|first10=Dwight|last11=Somers|first11=Michael J.|last12=Burns Wechsler|first12=Stephanie|last13=Weinstein|first13=David A.|last14=Wolfsdorf|first14=Joseph I.|last15=Watson|first15=Michael S.|title=Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics|journal=Genetics in Medicine|year=2014|issn=1098-3600|doi=10.1038/gim.2014.128}}</ref> | ||
*GSD type 1a is due to the deficiency of enzyme glucose-6-phosphatase (G6Pase).<ref name="pmid18449899">{{cite journal| author=Chou JY, Mansfield BC| title=Mutations in the glucose-6-phosphatase-alpha (G6PC) gene that cause type Ia glycogen storage disease. | journal=Hum Mutat | year= 2008 | volume= 29 | issue= 7 | pages= 921-30 | pmid=18449899 | doi=10.1002/humu.20772 | pmc=2475600 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18449899 }} </ref> | *GSD type 1a is due to the deficiency of enzyme [[glucose-6-phosphatase]] ([[Glucose-6-phosphatase|G6Pase]]).<ref name="pmid18449899">{{cite journal| author=Chou JY, Mansfield BC| title=Mutations in the glucose-6-phosphatase-alpha (G6PC) gene that cause type Ia glycogen storage disease. | journal=Hum Mutat | year= 2008 | volume= 29 | issue= 7 | pages= 921-30 | pmid=18449899 | doi=10.1002/humu.20772 | pmc=2475600 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18449899 }} </ref> | ||
*GDS type 1b is due to defect in glucose-6-phosphate translocase (T1 deficiency).<ref name="pmid10482962">{{cite journal| author=Veiga-da-Cunha M, Gerin I, Chen YT, Lee PJ, Leonard JV, Maire I et al.| title=The putative glucose 6-phosphate translocase gene is mutated in essentially all cases of glycogen storage disease type I non-a. | journal=Eur J Hum Genet | year= 1999 | volume= 7 | issue= 6 | pages= 717-23 | pmid=10482962 | doi=10.1038/sj.ejhg.5200366 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10482962 }} </ref><ref name="pmid11071391">{{cite journal| author=Janecke AR, Lindner M, Erdel M, Mayatepek E, Möslinger D, Podskarbi T et al.| title=Mutation analysis in glycogen storage disease type 1 non-a. | journal=Hum Genet | year= 2000 | volume= 107 | issue= 3 | pages= 285-9 | pmid=11071391 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11071391 }} </ref> | *GDS type 1b is due to defect in [[glucose-6-phosphate]] [[translocase]] (T1 deficiency).<ref name="pmid10482962">{{cite journal| author=Veiga-da-Cunha M, Gerin I, Chen YT, Lee PJ, Leonard JV, Maire I et al.| title=The putative glucose 6-phosphate translocase gene is mutated in essentially all cases of glycogen storage disease type I non-a. | journal=Eur J Hum Genet | year= 1999 | volume= 7 | issue= 6 | pages= 717-23 | pmid=10482962 | doi=10.1038/sj.ejhg.5200366 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10482962 }} </ref><ref name="pmid11071391">{{cite journal| author=Janecke AR, Lindner M, Erdel M, Mayatepek E, Möslinger D, Podskarbi T et al.| title=Mutation analysis in glycogen storage disease type 1 non-a. | journal=Hum Genet | year= 2000 | volume= 107 | issue= 3 | pages= 285-9 | pmid=11071391 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11071391 }} </ref> | ||
=== Mechanism of hypoglycemia === | === Mechanism of hypoglycemia === | ||
*G6Pase is primarily expressed in | *[[Glucose-6-phosphatase|G6Pase]] is primarily expressed in [[gluconeogenesis]] in the [[liver]] and [[kidney]]. It is also expressed to a lesser extent in the [[intestine]] and [[pancreas]].<ref name="pmid12373567">{{cite journal| author=Rake JP, Visser G, Labrune P, Leonard JV, Ullrich K, Smit GP| title=Glycogen storage disease type I: diagnosis, management, clinical course and outcome. Results of the European Study on Glycogen Storage Disease Type I (ESGSD I). | journal=Eur J Pediatr | year= 2002 | volume= 161 Suppl 1 | issue= | pages= S20-34 | pmid=12373567 | doi=10.1007/s00431-002-0999-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12373567 }} </ref><ref name="pmid12618563">{{cite journal| author=Wolfsdorf JI, Weinstein DA| title=Glycogen storage diseases. | journal=Rev Endocr Metab Disord | year= 2003 | volume= 4 | issue= 1 | pages= 95-102 | pmid=12618563 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12618563 }} </ref> | ||
*Glucose-6-phosphatase catalyzes the conversion of glucose-6-phosphate to glucose during glycogenolysis and gluconeogenesis. | *[[Glucose-6-phosphatase]] catalyzes the conversion of [[glucose-6-phosphate]] to [[glucose]] during [[glycogenolysis]] and [[gluconeogenesis]]. | ||
*This | *[[4|This d]]<nowiki/>efects hinders the conversion of [[glucose-6-phosphate]] to [[glucose]] in [[organs]]. | ||
*This leads to accumulation of glycogen in organs including liver, kidney, and intestine. | *This leads to accumulation of [[glycogen]] in organs including [[liver]], [[kidney]], and [[intestine]]. | ||
*The inability of glucose-6-phosphate to leave cells leads to severe fasting hypoglycemia. | *The inability of [[glucose-6-phosphate]] to leave cells leads to severe fasting [[hypoglycemia]]. | ||
*This also results in the development of various secondary metabolic and biochemical abnormalities including hyperlactacidemia, hyperuricemia, and hyperlipidemia. | *This also results in the development of various secondary [[metabolic]] and [[biochemical]] abnormalities including [[hyperlactacidemia]], [[hyperuricemia]], and [[hyperlipidemia]]. | ||
=== Mechanism of hyperuricemia === | === Mechanism of hyperuricemia === | ||
*Hyperuricemia in glycogen storage disease type 1 is due to:<ref name="pmid266162">{{cite journal| author=Roe TF, Kogut MD| title=The pathogenesis of hyperuricemia in glycogen storage disease, type I. | journal=Pediatr Res | year= 1977 | volume= 11 | issue= 5 | pages= 664-9 | pmid=266162 | doi=10.1203/00006450-197705000-00008 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=266162 }} </ref><ref name="pmid5225563">{{cite journal| author=Alepa FP, Howell RR, Klinenberg JR, Seegmiller JE| title=Relationships between glycogen storage disease and tophaceous gout. | journal=Am J Med | year= 1967 | volume= 42 | issue= 1 | pages= 58-66 | pmid=5225563 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5225563 }} </ref><ref name="pmid5224881">{{cite journal| author=Fine RN, Strauss J, Donnell GN| title=Hyperuricemia in glycogen-storage disease type 1. | journal=Am J Dis Child | year= 1966 | volume= 112 | issue= 6 | pages= 572-6 | pmid=5224881 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5224881 }} </ref><ref name="pmid6024734">{{cite journal| author=Jakovcic S, Sorensen LB| title=Studies of uric acid metabolism in glycogen storage disease associated with gouty arthritis. | journal=Arthritis Rheum | year= 1967 | volume= 10 | issue= 2 | pages= 129-34 | pmid=6024734 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6024734 }} </ref><ref name="KelleyRosenbloom1968">{{cite journal|last1=Kelley|first1=W.N.|last2=Rosenbloom|first2=F.M.|last3=Seegmiller|first3=J.E.|last4=Howell|first4=R. Rodney|title=Excessive production of uric acid in type I glycogen storage disease|journal=The Journal of Pediatrics|volume=72|issue=4|year=1968|pages=488–496|issn=00223476|doi=10.1016/S0022-3476(68)80339-7}}</ref><ref name="pmid2856925">{{cite journal| author=Cohen JL, Vinik A, Faller J, Fox IH| title=Hyperuricemia in glycogen storage disease type I. Contributions by hypoglycemia and hyperglucagonemia to increased urate production. | journal=J Clin Invest | year= 1985 | volume= 75 | issue= 1 | pages= 251-7 | pmid=2856925 | doi=10.1172/JCI111681 | pmc=423433 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2856925 }} </ref><ref name="pmid273863">{{cite journal| author=Benke PJ, Gold S| title=Uric acid metabolism in therapy of glycogen storage disease type I. | journal=Pediatr Res | year= 1978 | volume= 12 | issue= 3 | pages= 204-6 | pmid=273863 | doi=10.1203/00006450-197803000-00008 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=273863 }} </ref><ref name="Howell1965">{{cite journal|last1=Howell|first1=R. Rodney|title=The interrelationship of glycogen storage disease and gout|journal=Arthritis & Rheumatism|volume=8|issue=4|year=1965|pages=780–785|issn=00043591|doi=10.1002/art.1780080441}}</ref> | *[[Hyperuricemia]] in glycogen storage disease type 1 is due to:<ref name="pmid266162">{{cite journal| author=Roe TF, Kogut MD| title=The pathogenesis of hyperuricemia in glycogen storage disease, type I. | journal=Pediatr Res | year= 1977 | volume= 11 | issue= 5 | pages= 664-9 | pmid=266162 | doi=10.1203/00006450-197705000-00008 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=266162 }} </ref><ref name="pmid5225563">{{cite journal| author=Alepa FP, Howell RR, Klinenberg JR, Seegmiller JE| title=Relationships between glycogen storage disease and tophaceous gout. | journal=Am J Med | year= 1967 | volume= 42 | issue= 1 | pages= 58-66 | pmid=5225563 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5225563 }} </ref><ref name="pmid5224881">{{cite journal| author=Fine RN, Strauss J, Donnell GN| title=Hyperuricemia in glycogen-storage disease type 1. | journal=Am J Dis Child | year= 1966 | volume= 112 | issue= 6 | pages= 572-6 | pmid=5224881 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5224881 }} </ref><ref name="pmid6024734">{{cite journal| author=Jakovcic S, Sorensen LB| title=Studies of uric acid metabolism in glycogen storage disease associated with gouty arthritis. | journal=Arthritis Rheum | year= 1967 | volume= 10 | issue= 2 | pages= 129-34 | pmid=6024734 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6024734 }} </ref><ref name="KelleyRosenbloom1968">{{cite journal|last1=Kelley|first1=W.N.|last2=Rosenbloom|first2=F.M.|last3=Seegmiller|first3=J.E.|last4=Howell|first4=R. Rodney|title=Excessive production of uric acid in type I glycogen storage disease|journal=The Journal of Pediatrics|volume=72|issue=4|year=1968|pages=488–496|issn=00223476|doi=10.1016/S0022-3476(68)80339-7}}</ref><ref name="pmid2856925">{{cite journal| author=Cohen JL, Vinik A, Faller J, Fox IH| title=Hyperuricemia in glycogen storage disease type I. Contributions by hypoglycemia and hyperglucagonemia to increased urate production. | journal=J Clin Invest | year= 1985 | volume= 75 | issue= 1 | pages= 251-7 | pmid=2856925 | doi=10.1172/JCI111681 | pmc=423433 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2856925 }} </ref><ref name="pmid273863">{{cite journal| author=Benke PJ, Gold S| title=Uric acid metabolism in therapy of glycogen storage disease type I. | journal=Pediatr Res | year= 1978 | volume= 12 | issue= 3 | pages= 204-6 | pmid=273863 | doi=10.1203/00006450-197803000-00008 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=273863 }} </ref><ref name="Howell1965">{{cite journal|last1=Howell|first1=R. Rodney|title=The interrelationship of glycogen storage disease and gout|journal=Arthritis & Rheumatism|volume=8|issue=4|year=1965|pages=780–785|issn=00043591|doi=10.1002/art.1780080441}}</ref> | ||
**Decrease uric acid excretion: High | **Decrease [[uric acid]] [[excretion]]: High serum [[lactate]] and ketoacid levels cause a decrease in [[renal clearance]] of [[uric acid]]. | ||
** | **[[Uric acid]] overproduction | ||
===Hepatomegaly and liver disorders=== | ===Hepatomegaly and liver disorders=== | ||
*Impairment of glycogenolysis leads to the accumulation of fat and glycogen deposition resulting in characteristic hepatomegaly. | *Impairment of [[glycogenolysis]] leads to the accumulation of [[fat]] and [[glycogen]] deposition resulting in characteristic [[hepatomegaly]]. | ||
*Hepatomegaly is more pronounced when the child is young and decreases as the age progresses. The hepatomegaly leads to protrusion of the abdomen. | *[[Hepatomegaly]] is more pronounced when the child is young and decreases as the age progresses. The [[hepatomegaly]] leads to protrusion of the [[abdomen]]. | ||
*Patients with GSD type 1 may develop hepatic lesions including:<ref name="pmid12373567">{{cite journal| author=Rake JP, Visser G, Labrune P, Leonard JV, Ullrich K, Smit GP| title=Glycogen storage disease type I: diagnosis, management, clinical course and outcome. Results of the European Study on Glycogen Storage Disease Type I (ESGSD I). | journal=Eur J Pediatr | year= 2002 | volume= 161 Suppl 1 | issue= | pages= S20-34 | pmid=12373567 | doi=10.1007/s00431-002-0999-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12373567 }} </ref><ref name="pmid15877204">{{cite journal| author=Franco LM, Krishnamurthy V, Bali D, Weinstein DA, Arn P, Clary B et al.| title=Hepatocellular carcinoma in glycogen storage disease type Ia: a case series. | journal=J Inherit Metab Dis | year= 2005 | volume= 28 | issue= 2 | pages= 153-62 | pmid=15877204 | doi=10.1007/s10545-005-7500-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15877204 }} </ref><ref name="pmid17637480">{{cite journal| author=Reddy SK, Kishnani PS, Sullivan JA, Koeberl DD, Desai DM, Skinner MA et al.| title=Resection of hepatocellular adenoma in patients with glycogen storage disease type Ia. | journal=J Hepatol | year= 2007 | volume= 47 | issue= 5 | pages= 658-63 | pmid=17637480 | doi=10.1016/j.jhep.2007.05.012 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17637480 }} </ref><ref name="pmid11211215">{{cite journal| author=Kudo M| title=Hepatocellular adenoma in type Ia glycogen storage disease. | journal=J Gastroenterol | year= 2001 | volume= 36 | issue= 1 | pages= 65-6 | pmid=11211215 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11211215 }} </ref><ref name="pmid11428803">{{cite journal| author=Kelly PM, Poon FW| title=Hepatic tumours in glycogen storage disease type 1 (von Gierke's disease). | journal=Clin Radiol | year= 2001 | volume= 56 | issue= 6 | pages= 505-8 | pmid=11428803 | doi=10.1053/crad.2000.0457 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11428803 }} </ref><ref name="pmid12373570">{{cite journal| author=Lee PJ| title=Glycogen storage disease type I: pathophysiology of liver adenomas. | journal=Eur J Pediatr | year= 2002 | volume= 161 Suppl 1 | issue= | pages= S46-9 | pmid=12373570 | doi=10.1007/s00431-002-1002-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12373570 }} </ref> | *Patients with GSD type 1 may develop [[hepatic]] lesions including:<ref name="pmid12373567">{{cite journal| author=Rake JP, Visser G, Labrune P, Leonard JV, Ullrich K, Smit GP| title=Glycogen storage disease type I: diagnosis, management, clinical course and outcome. Results of the European Study on Glycogen Storage Disease Type I (ESGSD I). | journal=Eur J Pediatr | year= 2002 | volume= 161 Suppl 1 | issue= | pages= S20-34 | pmid=12373567 | doi=10.1007/s00431-002-0999-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12373567 }} </ref><ref name="pmid15877204">{{cite journal| author=Franco LM, Krishnamurthy V, Bali D, Weinstein DA, Arn P, Clary B et al.| title=Hepatocellular carcinoma in glycogen storage disease type Ia: a case series. | journal=J Inherit Metab Dis | year= 2005 | volume= 28 | issue= 2 | pages= 153-62 | pmid=15877204 | doi=10.1007/s10545-005-7500-2 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15877204 }} </ref><ref name="pmid17637480">{{cite journal| author=Reddy SK, Kishnani PS, Sullivan JA, Koeberl DD, Desai DM, Skinner MA et al.| title=Resection of hepatocellular adenoma in patients with glycogen storage disease type Ia. | journal=J Hepatol | year= 2007 | volume= 47 | issue= 5 | pages= 658-63 | pmid=17637480 | doi=10.1016/j.jhep.2007.05.012 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17637480 }} </ref><ref name="pmid11211215">{{cite journal| author=Kudo M| title=Hepatocellular adenoma in type Ia glycogen storage disease. | journal=J Gastroenterol | year= 2001 | volume= 36 | issue= 1 | pages= 65-6 | pmid=11211215 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11211215 }} </ref><ref name="pmid11428803">{{cite journal| author=Kelly PM, Poon FW| title=Hepatic tumours in glycogen storage disease type 1 (von Gierke's disease). | journal=Clin Radiol | year= 2001 | volume= 56 | issue= 6 | pages= 505-8 | pmid=11428803 | doi=10.1053/crad.2000.0457 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11428803 }} </ref><ref name="pmid12373570">{{cite journal| author=Lee PJ| title=Glycogen storage disease type I: pathophysiology of liver adenomas. | journal=Eur J Pediatr | year= 2002 | volume= 161 Suppl 1 | issue= | pages= S46-9 | pmid=12373570 | doi=10.1007/s00431-002-1002-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12373570 }} </ref> | ||
**Hepatocellular adenoma (most common) | **[[Hepatocellular adenoma]] (most common) | ||
** | **[[Hepatocellular carcinoma]] | ||
**Hepatoblastoma | **[[Hepatoblastoma]] | ||
**Focal fatty infiltration | **Focal [[fatty infiltration]] | ||
**Focal fatty sparing | **Focal fatty sparing | ||
**Focal nodular hyperplasia | **[[Focal nodular hyperplasia]] | ||
**Peliosis hepatis | **[[Peliosis hepatis]] | ||
*The prevalence of hepatocellular adenoma increases as the age progress. 70 - 80 % Patients have at least one lesion of hepatocellular adenoma by the time they reach the age of 25 years. | *The [[prevalence]] of [[hepatocellular adenoma]] increases as the age progress. 70 - 80 % Patients have at least one lesion of [[hepatocellular adenoma]] by the time they reach the age of 25 years. | ||
===Renal disorders=== | ===Renal disorders=== | ||
*Patients with GSD type 1 have renal manifestations early in childhood.<ref name="pmid8319728">{{cite journal| author=Reitsma-Bierens WC| title=Renal complications in glycogen storage disease type I. | journal=Eur J Pediatr | year= 1993 | volume= 152 Suppl 1 | issue= | pages= S60-2 | pmid=8319728 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8319728 }} </ref> | *Patients with GSD type 1 have [[renal]] manifestations early in childhood.<ref name="pmid8319728">{{cite journal| author=Reitsma-Bierens WC| title=Renal complications in glycogen storage disease type I. | journal=Eur J Pediatr | year= 1993 | volume= 152 Suppl 1 | issue= | pages= S60-2 | pmid=8319728 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8319728 }} </ref> | ||
*Glycogen deposits in kidneys leading to nephromegaly, which is usually detected by imaging techniques.<ref name="pmid1616830">{{cite journal| author=Reitsma-Bierens WC, Smit GP, Troelstra JA| title=Renal function and kidney size in glycogen storage disease type I. | journal=Pediatr Nephrol | year= 1992 | volume= 6 | issue= 3 | pages= 236-8 | pmid=1616830 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1616830 }} </ref><ref name="pmid3422104">{{cite journal| author=Chen YT, Coleman RA, Scheinman JI, Kolbeck PC, Sidbury JB| title=Renal disease in type I glycogen storage disease. | journal=N Engl J Med | year= 1988 | volume= 318 | issue= 1 | pages= 7-11 | pmid=3422104 | doi=10.1056/NEJM198801073180102 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3422104 }} </ref> | *[[Glycogen]] deposits in [[kidneys]] leading to [[nephromegaly]], which is usually detected by [[imaging techniques]].<ref name="pmid1616830">{{cite journal| author=Reitsma-Bierens WC, Smit GP, Troelstra JA| title=Renal function and kidney size in glycogen storage disease type I. | journal=Pediatr Nephrol | year= 1992 | volume= 6 | issue= 3 | pages= 236-8 | pmid=1616830 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1616830 }} </ref><ref name="pmid3422104">{{cite journal| author=Chen YT, Coleman RA, Scheinman JI, Kolbeck PC, Sidbury JB| title=Renal disease in type I glycogen storage disease. | journal=N Engl J Med | year= 1988 | volume= 318 | issue= 1 | pages= 7-11 | pmid=3422104 | doi=10.1056/NEJM198801073180102 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3422104 }} </ref> | ||
*There is a progressive decrease in urinary citrate excretion as the age increases. Hypocitraturia along with hypercalciuria leads to nephrolithiasis and nephrocalcinosis.<ref name="pmid11241046">{{cite journal| author=Weinstein DA, Somers MJ, Wolfsdorf JI| title=Decreased urinary citrate excretion in type 1a glycogen storage disease. | journal=J Pediatr | year= 2001 | volume= 138 | issue= 3 | pages= 378-82 | pmid=11241046 | doi=10.1067/mpd.2001.111322 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11241046 }} </ref><ref name="pmid8747109">{{cite journal| author=Lee PJ, Dalton RN, Shah V, Hindmarsh PC, Leonard JV| title=Glomerular and tubular function in glycogen storage disease. | journal=Pediatr Nephrol | year= 1995 | volume= 9 | issue= 6 | pages= 705-10 | pmid=8747109 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8747109 }} </ref><ref name="pmid8441093">{{cite journal| author=Restaino I, Kaplan BS, Stanley C, Baker L| title=Nephrolithiasis, hypocitraturia, and a distal renal tubular acidification defect in type 1 glycogen storage disease. | journal=J Pediatr | year= 1993 | volume= 122 | issue= 3 | pages= 392-6 | pmid=8441093 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8441093 }} </ref> | *There is a progressive decrease in [[urinary]] [[citrate]] [[excretion]] as the age increases. [[Hypocitraturia]] along with [[hypercalciuria]] leads to [[nephrolithiasis]] and [[nephrocalcinosis]].<ref name="pmid11241046">{{cite journal| author=Weinstein DA, Somers MJ, Wolfsdorf JI| title=Decreased urinary citrate excretion in type 1a glycogen storage disease. | journal=J Pediatr | year= 2001 | volume= 138 | issue= 3 | pages= 378-82 | pmid=11241046 | doi=10.1067/mpd.2001.111322 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11241046 }} </ref><ref name="pmid8747109">{{cite journal| author=Lee PJ, Dalton RN, Shah V, Hindmarsh PC, Leonard JV| title=Glomerular and tubular function in glycogen storage disease. | journal=Pediatr Nephrol | year= 1995 | volume= 9 | issue= 6 | pages= 705-10 | pmid=8747109 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8747109 }} </ref><ref name="pmid8441093">{{cite journal| author=Restaino I, Kaplan BS, Stanley C, Baker L| title=Nephrolithiasis, hypocitraturia, and a distal renal tubular acidification defect in type 1 glycogen storage disease. | journal=J Pediatr | year= 1993 | volume= 122 | issue= 3 | pages= 392-6 | pmid=8441093 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8441093 }} </ref> | ||
*Glycogen storage and metabolic disturbances in patients with GSD type 1 leads to progressive glomerular injury and finally end-stage renal disease requiring renal transplantation. | *[[Glycogen]] storage and [[metabolic]] disturbances in patients with GSD type 1 leads to progressive [[glomerular injury]] and finally end-stage renal disease requiring [[renal transplantation]]. | ||
===Hematologic Disorders=== | ===Hematologic Disorders=== | ||
====Anemia==== | ====Anemia==== | ||
*Anemia in GSD type 1 is due to an array of factors including:<ref name="KishnaniAustin2014">{{cite journal|last1=Kishnani|first1=Priya S.|last2=Austin|first2=Stephanie L.|last3=Abdenur|first3=Jose E.|last4=Arn|first4=Pamela|last5=Bali|first5=Deeksha S.|last6=Boney|first6=Anne|last7=Chung|first7=Wendy K.|last8=Dagli|first8=Aditi I.|last9=Dale|first9=David|last10=Koeberl|first10=Dwight|last11=Somers|first11=Michael J.|last12=Burns Wechsler|first12=Stephanie|last13=Weinstein|first13=David A.|last14=Wolfsdorf|first14=Joseph I.|last15=Watson|first15=Michael S.|title=Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics|journal=Genetics in Medicine|year=2014|issn=1098-3600|doi=10.1038/gim.2014.128}}</ref><ref name="pmid22678084">{{cite journal| author=Wang DQ, Carreras CT, Fiske LM, Austin S, Boree D, Kishnani PS et al.| title=Characterization and pathogenesis of anemia in glycogen storage disease type Ia and Ib. | journal=Genet Med | year= 2012 | volume= 14 | issue= 9 | pages= 795-9 | pmid=22678084 | doi=10.1038/gim.2012.41 | pmc=3808879 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22678084 }} </ref> | *[[Anemia]] in GSD type 1 is due to an array of factors including:<ref name="KishnaniAustin2014">{{cite journal|last1=Kishnani|first1=Priya S.|last2=Austin|first2=Stephanie L.|last3=Abdenur|first3=Jose E.|last4=Arn|first4=Pamela|last5=Bali|first5=Deeksha S.|last6=Boney|first6=Anne|last7=Chung|first7=Wendy K.|last8=Dagli|first8=Aditi I.|last9=Dale|first9=David|last10=Koeberl|first10=Dwight|last11=Somers|first11=Michael J.|last12=Burns Wechsler|first12=Stephanie|last13=Weinstein|first13=David A.|last14=Wolfsdorf|first14=Joseph I.|last15=Watson|first15=Michael S.|title=Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics|journal=Genetics in Medicine|year=2014|issn=1098-3600|doi=10.1038/gim.2014.128}}</ref><ref name="pmid22678084">{{cite journal| author=Wang DQ, Carreras CT, Fiske LM, Austin S, Boree D, Kishnani PS et al.| title=Characterization and pathogenesis of anemia in glycogen storage disease type Ia and Ib. | journal=Genet Med | year= 2012 | volume= 14 | issue= 9 | pages= 795-9 | pmid=22678084 | doi=10.1038/gim.2012.41 | pmc=3808879 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22678084 }} </ref> | ||
**The restricted nature of the diet | **The restricted nature of the diet | ||
**Chronic lactic acidosis | **Chronic [[lactic acidosis]] | ||
**Renal disorders | **[[Renal]] disorders | ||
**Bleeding diathesis | **[[Bleeding diathesis]] | ||
**Chronic nature of the illness | **Chronic nature of the illness | ||
**Suboptimal metabolic control | **Suboptimal metabolic control | ||
**Hepatic adenomas | **[[Hepatic adenomas]] | ||
**Inflammatory bowel disease (specifically in GSD type 1b) | **[[Inflammatory bowel disease]] (specifically in GSD type 1b) | ||
*Abnormal expression of | *Abnormal expression of [[hepcidin]] in GSD type 1 leads to refractory [[iron deficiency anemia]].<ref name="pmid12393428">{{cite journal| author=Weinstein DA, Roy CN, Fleming MD, Loda MF, Wolfsdorf JI, Andrews NC| title=Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. | journal=Blood | year= 2002 | volume= 100 | issue= 10 | pages= 3776-81 | pmid=12393428 | doi=10.1182/blood-2002-04-1260 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12393428 }} </ref> | ||
*In GSD type 1b associated with inflammatory bowel disease is believed to be due to Interleukin-6. Increased expression of Interleukin-6 due to inflammation leads to upregulation of hepcidin leading to anemia. | *In GSD type 1b associated with [[inflammatory bowel disease]] is believed to be due to [[Interleukin-6]]. Increased expression of [[Interleukin-6]] due to [[inflammation]] leads to [[upregulation]] of [[hepcidin]] leading to [[anemia]]. | ||
====Bleeding diathesis==== | ====Bleeding diathesis==== | ||
*Bleeding diathesis in GSD type 1 secondary to metabolic abnormalities and include:<ref name="pmid4350560">{{cite journal| author=Czapek EE, Deykin D, Salzman EW| title=Platelet dysfunction in glycogen storage disease type I. | journal=Blood | year= 1973 | volume= 41 | issue= 2 | pages= 235-47 | pmid=4350560 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4350560 }} </ref><ref name="pmid4212074">{{cite journal| author=Corby DG, Putnam CW, Greene HL| title=Impaired platelet function in glucose-6-phosphatase deficiency. | journal=J Pediatr | year= 1974 | volume= 85 | issue= 1 | pages= 71-6 | pmid=4212074 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4212074 }} </ref><ref name="pmid942229">{{cite journal| author=Hutton RA, Macnab AJ, Rivers RP| title=Defect of platelet function associated with chronic hypoglycaemia. | journal=Arch Dis Child | year= 1976 | volume= 51 | issue= 1 | pages= 49-55 | pmid=942229 | doi= | pmc=1545862 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=942229 }} </ref> | *[[Bleeding diathesis]] in GSD type 1 secondary to metabolic abnormalities and include:<ref name="pmid4350560">{{cite journal| author=Czapek EE, Deykin D, Salzman EW| title=Platelet dysfunction in glycogen storage disease type I. | journal=Blood | year= 1973 | volume= 41 | issue= 2 | pages= 235-47 | pmid=4350560 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4350560 }} </ref><ref name="pmid4212074">{{cite journal| author=Corby DG, Putnam CW, Greene HL| title=Impaired platelet function in glucose-6-phosphatase deficiency. | journal=J Pediatr | year= 1974 | volume= 85 | issue= 1 | pages= 71-6 | pmid=4212074 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4212074 }} </ref><ref name="pmid942229">{{cite journal| author=Hutton RA, Macnab AJ, Rivers RP| title=Defect of platelet function associated with chronic hypoglycaemia. | journal=Arch Dis Child | year= 1976 | volume= 51 | issue= 1 | pages= 49-55 | pmid=942229 | doi= | pmc=1545862 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=942229 }} </ref> | ||
*Acquired platelet dysfunction with prolonged bleeding times | *Acquired [[platelet]] dysfunction with [[Bleeding time|prolonged bleeding times]] | ||
*Decreased platelet adhesiveness | *Decreased [[platelet]] adhesiveness | ||
*Abnormal aggregation of platelets | *Abnormal aggregation of [[platelets]] | ||
====Neutropenia and neutrophil dysfunction==== | ====Neutropenia and neutrophil dysfunction==== | ||
*Neutropenia and neutrophil dysfunction is specific | *[[Neutropenia]] and [[neutrophil]] dysfunction is specific of GSD type 1b.<ref name="pmid12373578">{{cite journal| author=Visser G, Rake JP, Labrune P, Leonard JV, Moses S, Ullrich K et al.| title=Granulocyte colony-stimulating factor in glycogen storage disease type 1b. Results of the European Study on Glycogen Storage Disease Type 1. | journal=Eur J Pediatr | year= 2002 | volume= 161 Suppl 1 | issue= | pages= S83-7 | pmid=12373578 | doi=10.1007/s00431-002-1010-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12373578 }} </ref> | ||
*Neutropenia and neutrophil dysfunction in glycogen storage disease type Ib is thought to be due to loss of glucose-6-phosphate translocase activity leading to:<ref name="pmid19741523">{{cite journal| author=Chou JY, Jun HS, Mansfield BC| title=Neutropenia in type Ib glycogen storage disease. | journal=Curr Opin Hematol | year= 2010 | volume= 17 | issue= 1 | pages= 36-42 | pmid=19741523 | doi=10.1097/MOH.0b013e328331df85 | pmc=3099242 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19741523 }} </ref> | *[[Neutropenia]] and [[neutrophil]] dysfunction in glycogen storage disease type Ib is thought to be due to loss of [[glucose-6-phosphate]] [[translocase]] activity leading to:<ref name="pmid19741523">{{cite journal| author=Chou JY, Jun HS, Mansfield BC| title=Neutropenia in type Ib glycogen storage disease. | journal=Curr Opin Hematol | year= 2010 | volume= 17 | issue= 1 | pages= 36-42 | pmid=19741523 | doi=10.1097/MOH.0b013e328331df85 | pmc=3099242 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19741523 }} </ref> | ||
**Enhanced endoplasmic reticulum stress | **Enhanced [[endoplasmic reticulum]] stress | ||
**Oxidative stress | **[[Oxidative stress]] | ||
**Apoptosis of neutrophils | **[[Apoptosis]] of [[neutrophils]] | ||
*Patients with GSD type 1b associated with neutropenia are at increased risk of:<ref name="pmid8975948">{{cite journal| author=Franceschini R, Gianetta E, Pastorino A, Dallegri F, Cataldi A, Corsini G et al.| title=Crohn's-like colitis in glycogen storage disease Ib: a case report. | journal=Hepatogastroenterology | year= 1996 | volume= 43 | issue= 12 | pages= 1461-4 | pmid=8975948 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8975948 }} </ref><ref name="pmid12373579">{{cite journal| author=Dieckgraefe BK, Korzenik JR, Husain A, Dieruf L| title=Association of glycogen storage disease 1b and Crohn disease: results of a North American survey. | journal=Eur J Pediatr | year= 2002 | volume= 161 Suppl 1 | issue= | pages= S88-92 | pmid=12373579 | doi=10.1007/s00431-002-1011-z | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12373579 }} </ref> | *Patients with GSD type 1b associated with [[neutropenia]] are at increased risk of:<ref name="pmid8975948">{{cite journal| author=Franceschini R, Gianetta E, Pastorino A, Dallegri F, Cataldi A, Corsini G et al.| title=Crohn's-like colitis in glycogen storage disease Ib: a case report. | journal=Hepatogastroenterology | year= 1996 | volume= 43 | issue= 12 | pages= 1461-4 | pmid=8975948 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8975948 }} </ref><ref name="pmid12373579">{{cite journal| author=Dieckgraefe BK, Korzenik JR, Husain A, Dieruf L| title=Association of glycogen storage disease 1b and Crohn disease: results of a North American survey. | journal=Eur J Pediatr | year= 2002 | volume= 161 Suppl 1 | issue= | pages= S88-92 | pmid=12373579 | doi=10.1007/s00431-002-1011-z | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12373579 }} </ref> | ||
**Infections | **[[Infections]] | ||
**Gingivitis | **[[Gingivitis]] | ||
**Mouth ulcers | **[[Mouth ulcers]] | ||
**Upper respiratory infections | **[[Upper respiratory infection|Upper respiratory infections]] | ||
**Deep abscesses | **[[Deep abscess|Deep abscesses]] | ||
**Enterocolitis | **[[Enterocolitis]] | ||
*Also, there is dysfunction of monocytes leads to:<ref name="pmid2164043">{{cite journal| author=Kilpatrick L, Garty BZ, Lundquist KF, Hunter K, Stanley CA, Baker L et al.| title=Impaired metabolic function and signaling defects in phagocytic cells in glycogen storage disease type 1b. | journal=J Clin Invest | year= 1990 | volume= 86 | issue= 1 | pages= 196-202 | pmid=2164043 | doi=10.1172/JCI114684 | pmc=296707 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2164043 }} </ref> | *Also, there is dysfunction of monocytes leads to:<ref name="pmid2164043">{{cite journal| author=Kilpatrick L, Garty BZ, Lundquist KF, Hunter K, Stanley CA, Baker L et al.| title=Impaired metabolic function and signaling defects in phagocytic cells in glycogen storage disease type 1b. | journal=J Clin Invest | year= 1990 | volume= 86 | issue= 1 | pages= 196-202 | pmid=2164043 | doi=10.1172/JCI114684 | pmc=296707 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2164043 }} </ref> | ||
**Granuloma formation | **[[Granuloma]] formation | ||
**Chronic inflammatory responses | **[[Chronic inflammation|Chronic inflammatory responses]] | ||
==Genetics== | ==Genetics== | ||
*80% Cases of GSD 1 are of GSD type 1a.<ref name="pmid10322403">{{cite journal| author=Mansfield BC| title=Molecular Genetics of Type 1 Glycogen Storage Diseases. | journal=Trends Endocrinol Metab | year= 1999 | volume= 10 | issue= 3 | pages= 104-113 | pmid=10322403 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10322403 }} </ref> | *80% Cases of GSD 1 are of GSD type 1a.<ref name="pmid10322403">{{cite journal| author=Mansfield BC| title=Molecular Genetics of Type 1 Glycogen Storage Diseases. | journal=Trends Endocrinol Metab | year= 1999 | volume= 10 | issue= 3 | pages= 104-113 | pmid=10322403 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10322403 }} </ref> | ||
*G6Pase gene mutation is responsible for GSD type 1a and is located on chromosome locus 17q21.<ref name="pmid18449899">{{cite journal| author=Chou JY, Mansfield BC| title=Mutations in the glucose-6-phosphatase-alpha (G6PC) gene that cause type Ia glycogen storage disease. | journal=Hum Mutat | year= 2008 | volume= 29 | issue= 7 | pages= 921-30 | pmid=18449899 | doi=10.1002/humu.20772 | pmc=2475600 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18449899 }} </ref> | *[[Glucose-1-phosphatase|G6Pase]] [[gene mutation]] is responsible for GSD type 1a and is located on [[chromosome]] locus 17q21.<ref name="pmid18449899">{{cite journal| author=Chou JY, Mansfield BC| title=Mutations in the glucose-6-phosphatase-alpha (G6PC) gene that cause type Ia glycogen storage disease. | journal=Hum Mutat | year= 2008 | volume= 29 | issue= 7 | pages= 921-30 | pmid=18449899 | doi=10.1002/humu.20772 | pmc=2475600 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18449899 }} </ref> | ||
*Glucose-6-phosphate translocase defect is responsible for GSD type 1b and is located on chromosome locus 11q23.<ref name="pmid9758626">{{cite journal| author=Veiga-da-Cunha M, Gerin I, Chen YT, de Barsy T, de Lonlay P, Dionisi-Vici C et al.| title=A gene on chromosome 11q23 coding for a putative glucose- 6-phosphate translocase is mutated in glycogen-storage disease types Ib and Ic. | journal=Am J Hum Genet | year= 1998 | volume= 63 | issue= 4 | pages= 976-83 | pmid=9758626 | doi=10.1086/302068 | pmc=1377500 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9758626 }} </ref><ref name="pmid11071391">{{cite journal| author=Janecke AR, Lindner M, Erdel M, Mayatepek E, Möslinger D, Podskarbi T et al.| title=Mutation analysis in glycogen storage disease type 1 non-a. | journal=Hum Genet | year= 2000 | volume= 107 | issue= 3 | pages= 285-9 | pmid=11071391 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11071391 }} </ref> | *[[Glucose-6-phosphate]] [[translocase]] defect is responsible for GSD type 1b and is located on [[chromosome]] locus 11q23.<ref name="pmid9758626">{{cite journal| author=Veiga-da-Cunha M, Gerin I, Chen YT, de Barsy T, de Lonlay P, Dionisi-Vici C et al.| title=A gene on chromosome 11q23 coding for a putative glucose- 6-phosphate translocase is mutated in glycogen-storage disease types Ib and Ic. | journal=Am J Hum Genet | year= 1998 | volume= 63 | issue= 4 | pages= 976-83 | pmid=9758626 | doi=10.1086/302068 | pmc=1377500 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9758626 }} </ref><ref name="pmid11071391">{{cite journal| author=Janecke AR, Lindner M, Erdel M, Mayatepek E, Möslinger D, Podskarbi T et al.| title=Mutation analysis in glycogen storage disease type 1 non-a. | journal=Hum Genet | year= 2000 | volume= 107 | issue= 3 | pages= 285-9 | pmid=11071391 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11071391 }} </ref> | ||
*GSD type 1 follows an autosomal recessive pattern. | *GSD type 1 follows an [[autosomal recessive]] pattern. | ||
==Gross Pathology== | ==Gross Pathology== | ||
On microscopic histopathological analysis, the features of glycogen storage disease type 1 include hepatomegaly. Hepatomegaly decreases as age increases.<ref name="KishnaniAustin2014">{{cite journal|last1=Kishnani|first1=Priya S.|last2=Austin|first2=Stephanie L.|last3=Abdenur|first3=Jose E.|last4=Arn|first4=Pamela|last5=Bali|first5=Deeksha S.|last6=Boney|first6=Anne|last7=Chung|first7=Wendy K.|last8=Dagli|first8=Aditi I.|last9=Dale|first9=David|last10=Koeberl|first10=Dwight|last11=Somers|first11=Michael J.|last12=Burns Wechsler|first12=Stephanie|last13=Weinstein|first13=David A.|last14=Wolfsdorf|first14=Joseph I.|last15=Watson|first15=Michael S.|title=Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics|journal=Genetics in Medicine|year=2014|issn=1098-3600|doi=10.1038/gim.2014.128}}</ref> | On microscopic histopathological analysis, the features of glycogen storage disease type 1 include [[hepatomegaly]]. [[Hepatomegaly]] decreases as age increases.<ref name="KishnaniAustin2014">{{cite journal|last1=Kishnani|first1=Priya S.|last2=Austin|first2=Stephanie L.|last3=Abdenur|first3=Jose E.|last4=Arn|first4=Pamela|last5=Bali|first5=Deeksha S.|last6=Boney|first6=Anne|last7=Chung|first7=Wendy K.|last8=Dagli|first8=Aditi I.|last9=Dale|first9=David|last10=Koeberl|first10=Dwight|last11=Somers|first11=Michael J.|last12=Burns Wechsler|first12=Stephanie|last13=Weinstein|first13=David A.|last14=Wolfsdorf|first14=Joseph I.|last15=Watson|first15=Michael S.|title=Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics|journal=Genetics in Medicine|year=2014|issn=1098-3600|doi=10.1038/gim.2014.128}}</ref> | ||
==Microscopic Pathology== | ==Microscopic Pathology== | ||
*On microscopic histopathological analysis, the features of glycogen storage disease type 1 include:<ref name="pmid21599942">{{cite journal| author=Froissart R, Piraud M, Boudjemline AM, Vianey-Saban C, Petit F, Hubert-Buron A et al.| title=Glucose-6-phosphatase deficiency. | journal=Orphanet J Rare Dis | year= 2011 | volume= 6 | issue= | pages= 27 | pmid=21599942 | doi=10.1186/1750-1172-6-27 | pmc=3118311 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21599942 }} </ref><ref name="pmid17552001">{{cite journal| author=Ozen H| title=Glycogen storage diseases: new perspectives. | journal=World J Gastroenterol | year= 2007 | volume= 13 | issue= 18 | pages= 2541-53 | pmid=17552001 | doi= | pmc=4146814 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17552001 }} </ref><ref>Bali DS, Chen YT, Austin S, et al. Glycogen Storage Disease Type I. 2006 Apr 19 [Updated 2016 Aug 25]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1312/</ref> | *On microscopic histopathological analysis, the features of glycogen storage disease type 1 include:<ref name="pmid21599942">{{cite journal| author=Froissart R, Piraud M, Boudjemline AM, Vianey-Saban C, Petit F, Hubert-Buron A et al.| title=Glucose-6-phosphatase deficiency. | journal=Orphanet J Rare Dis | year= 2011 | volume= 6 | issue= | pages= 27 | pmid=21599942 | doi=10.1186/1750-1172-6-27 | pmc=3118311 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21599942 }} </ref><ref name="pmid17552001">{{cite journal| author=Ozen H| title=Glycogen storage diseases: new perspectives. | journal=World J Gastroenterol | year= 2007 | volume= 13 | issue= 18 | pages= 2541-53 | pmid=17552001 | doi= | pmc=4146814 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17552001 }} </ref><ref>Bali DS, Chen YT, Austin S, et al. Glycogen Storage Disease Type I. 2006 Apr 19 [Updated 2016 Aug 25]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1312/</ref> | ||
**Distended liver cells by glycogen and fat | **Distended [[liver cells]] by [[glycogen]] and [[fat]] | ||
**PAS positive and diastase sensitive glycogen distributed uniformly within the cytoplasm | **[[PAS]] positive and [[diastase]] sensitive [[glycogen]] distributed uniformly within the [[cytoplasm]] | ||
**Normal or mildly increased glycogen as compared with that seen in other liver GSDs (especially GSDIII and GSDIX) | **Normal or mildly increased [[glycogen]] as compared with that seen in other liver [[Glycogen storage disease|GSDs]] (especially GSDIII and GSDIX) | ||
**Large and numerous lipid vacuoles | **Large and numerous [[lipid vacuoles]] | ||
**No fibrosis and cirrhosis | **No [[fibrosis]] and [[cirrhosis]] is present | ||
==References== | ==References== |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Pathophysiology
- Glycogen storage disease type 1 (GSD 1) results due to defects in either hydrolysis or transport of glucose-6-phosphate.[1][2]
- GSD type 1a is due to the deficiency of enzyme glucose-6-phosphatase (G6Pase).[3]
- GDS type 1b is due to defect in glucose-6-phosphate translocase (T1 deficiency).[4][5]
Mechanism of hypoglycemia
- G6Pase is primarily expressed in gluconeogenesis in the liver and kidney. It is also expressed to a lesser extent in the intestine and pancreas.[6][7]
- Glucose-6-phosphatase catalyzes the conversion of glucose-6-phosphate to glucose during glycogenolysis and gluconeogenesis.
- This defects hinders the conversion of glucose-6-phosphate to glucose in organs.
- This leads to accumulation of glycogen in organs including liver, kidney, and intestine.
- The inability of glucose-6-phosphate to leave cells leads to severe fasting hypoglycemia.
- This also results in the development of various secondary metabolic and biochemical abnormalities including hyperlactacidemia, hyperuricemia, and hyperlipidemia.
Mechanism of hyperuricemia
Hepatomegaly and liver disorders
- Impairment of glycogenolysis leads to the accumulation of fat and glycogen deposition resulting in characteristic hepatomegaly.
- Hepatomegaly is more pronounced when the child is young and decreases as the age progresses. The hepatomegaly leads to protrusion of the abdomen.
- Patients with GSD type 1 may develop hepatic lesions including:[6][16][17][18][19][20]
- Hepatocellular adenoma (most common)
- Hepatocellular carcinoma
- Hepatoblastoma
- Focal fatty infiltration
- Focal fatty sparing
- Focal nodular hyperplasia
- Peliosis hepatis
- The prevalence of hepatocellular adenoma increases as the age progress. 70 - 80 % Patients have at least one lesion of hepatocellular adenoma by the time they reach the age of 25 years.
Renal disorders
- Patients with GSD type 1 have renal manifestations early in childhood.[21]
- Glycogen deposits in kidneys leading to nephromegaly, which is usually detected by imaging techniques.[22][23]
- There is a progressive decrease in urinary citrate excretion as the age increases. Hypocitraturia along with hypercalciuria leads to nephrolithiasis and nephrocalcinosis.[24][25][26]
- Glycogen storage and metabolic disturbances in patients with GSD type 1 leads to progressive glomerular injury and finally end-stage renal disease requiring renal transplantation.
Hematologic Disorders
Anemia
- Anemia in GSD type 1 is due to an array of factors including:[2][27]
- The restricted nature of the diet
- Chronic lactic acidosis
- Renal disorders
- Bleeding diathesis
- Chronic nature of the illness
- Suboptimal metabolic control
- Hepatic adenomas
- Inflammatory bowel disease (specifically in GSD type 1b)
- Abnormal expression of hepcidin in GSD type 1 leads to refractory iron deficiency anemia.[28]
- In GSD type 1b associated with inflammatory bowel disease is believed to be due to Interleukin-6. Increased expression of Interleukin-6 due to inflammation leads to upregulation of hepcidin leading to anemia.
Bleeding diathesis
- Bleeding diathesis in GSD type 1 secondary to metabolic abnormalities and include:[29][30][31]
- Acquired platelet dysfunction with prolonged bleeding times
- Decreased platelet adhesiveness
- Abnormal aggregation of platelets
Neutropenia and neutrophil dysfunction
- Neutropenia and neutrophil dysfunction is specific of GSD type 1b.[32]
- Neutropenia and neutrophil dysfunction in glycogen storage disease type Ib is thought to be due to loss of glucose-6-phosphate translocase activity leading to:[33]
- Enhanced endoplasmic reticulum stress
- Oxidative stress
- Apoptosis of neutrophils
- Patients with GSD type 1b associated with neutropenia are at increased risk of:[34][35]
- Also, there is dysfunction of monocytes leads to:[36]
- Granuloma formation
- Chronic inflammatory responses
Genetics
- 80% Cases of GSD 1 are of GSD type 1a.[37]
- G6Pase gene mutation is responsible for GSD type 1a and is located on chromosome locus 17q21.[3]
- Glucose-6-phosphate translocase defect is responsible for GSD type 1b and is located on chromosome locus 11q23.[38][5]
- GSD type 1 follows an autosomal recessive pattern.
Gross Pathology
On microscopic histopathological analysis, the features of glycogen storage disease type 1 include hepatomegaly. Hepatomegaly decreases as age increases.[2]
Microscopic Pathology
- On microscopic histopathological analysis, the features of glycogen storage disease type 1 include:[39][40][41]
- Distended liver cells by glycogen and fat
- PAS positive and diastase sensitive glycogen distributed uniformly within the cytoplasm
- Normal or mildly increased glycogen as compared with that seen in other liver GSDs (especially GSDIII and GSDIX)
- Large and numerous lipid vacuoles
- No fibrosis and cirrhosis is present
References
- ↑ Moses SW (2002). "Historical highlights and unsolved problems in glycogen storage disease type 1". Eur J Pediatr. 161 Suppl 1: S2–9. doi:10.1007/s00431-002-0997-6. PMID 12373565.
- ↑ 2.0 2.1 2.2 Kishnani, Priya S.; Austin, Stephanie L.; Abdenur, Jose E.; Arn, Pamela; Bali, Deeksha S.; Boney, Anne; Chung, Wendy K.; Dagli, Aditi I.; Dale, David; Koeberl, Dwight; Somers, Michael J.; Burns Wechsler, Stephanie; Weinstein, David A.; Wolfsdorf, Joseph I.; Watson, Michael S. (2014). "Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics". Genetics in Medicine. doi:10.1038/gim.2014.128. ISSN 1098-3600.
- ↑ 3.0 3.1 Chou JY, Mansfield BC (2008). "Mutations in the glucose-6-phosphatase-alpha (G6PC) gene that cause type Ia glycogen storage disease". Hum Mutat. 29 (7): 921–30. doi:10.1002/humu.20772. PMC 2475600. PMID 18449899.
- ↑ Veiga-da-Cunha M, Gerin I, Chen YT, Lee PJ, Leonard JV, Maire I; et al. (1999). "The putative glucose 6-phosphate translocase gene is mutated in essentially all cases of glycogen storage disease type I non-a". Eur J Hum Genet. 7 (6): 717–23. doi:10.1038/sj.ejhg.5200366. PMID 10482962.
- ↑ 5.0 5.1 Janecke AR, Lindner M, Erdel M, Mayatepek E, Möslinger D, Podskarbi T; et al. (2000). "Mutation analysis in glycogen storage disease type 1 non-a". Hum Genet. 107 (3): 285–9. PMID 11071391.
- ↑ 6.0 6.1 Rake JP, Visser G, Labrune P, Leonard JV, Ullrich K, Smit GP (2002). "Glycogen storage disease type I: diagnosis, management, clinical course and outcome. Results of the European Study on Glycogen Storage Disease Type I (ESGSD I)". Eur J Pediatr. 161 Suppl 1: S20–34. doi:10.1007/s00431-002-0999-4. PMID 12373567.
- ↑ Wolfsdorf JI, Weinstein DA (2003). "Glycogen storage diseases". Rev Endocr Metab Disord. 4 (1): 95–102. PMID 12618563.
- ↑ Roe TF, Kogut MD (1977). "The pathogenesis of hyperuricemia in glycogen storage disease, type I." Pediatr Res. 11 (5): 664–9. doi:10.1203/00006450-197705000-00008. PMID 266162.
- ↑ Alepa FP, Howell RR, Klinenberg JR, Seegmiller JE (1967). "Relationships between glycogen storage disease and tophaceous gout". Am J Med. 42 (1): 58–66. PMID 5225563.
- ↑ Fine RN, Strauss J, Donnell GN (1966). "Hyperuricemia in glycogen-storage disease type 1". Am J Dis Child. 112 (6): 572–6. PMID 5224881.
- ↑ Jakovcic S, Sorensen LB (1967). "Studies of uric acid metabolism in glycogen storage disease associated with gouty arthritis". Arthritis Rheum. 10 (2): 129–34. PMID 6024734.
- ↑ Kelley, W.N.; Rosenbloom, F.M.; Seegmiller, J.E.; Howell, R. Rodney (1968). "Excessive production of uric acid in type I glycogen storage disease". The Journal of Pediatrics. 72 (4): 488–496. doi:10.1016/S0022-3476(68)80339-7. ISSN 0022-3476.
- ↑ Cohen JL, Vinik A, Faller J, Fox IH (1985). "Hyperuricemia in glycogen storage disease type I. Contributions by hypoglycemia and hyperglucagonemia to increased urate production". J Clin Invest. 75 (1): 251–7. doi:10.1172/JCI111681. PMC 423433. PMID 2856925.
- ↑ Benke PJ, Gold S (1978). "Uric acid metabolism in therapy of glycogen storage disease type I." Pediatr Res. 12 (3): 204–6. doi:10.1203/00006450-197803000-00008. PMID 273863.
- ↑ Howell, R. Rodney (1965). "The interrelationship of glycogen storage disease and gout". Arthritis & Rheumatism. 8 (4): 780–785. doi:10.1002/art.1780080441. ISSN 0004-3591.
- ↑ Franco LM, Krishnamurthy V, Bali D, Weinstein DA, Arn P, Clary B; et al. (2005). "Hepatocellular carcinoma in glycogen storage disease type Ia: a case series". J Inherit Metab Dis. 28 (2): 153–62. doi:10.1007/s10545-005-7500-2. PMID 15877204.
- ↑ Reddy SK, Kishnani PS, Sullivan JA, Koeberl DD, Desai DM, Skinner MA; et al. (2007). "Resection of hepatocellular adenoma in patients with glycogen storage disease type Ia". J Hepatol. 47 (5): 658–63. doi:10.1016/j.jhep.2007.05.012. PMID 17637480.
- ↑ Kudo M (2001). "Hepatocellular adenoma in type Ia glycogen storage disease". J Gastroenterol. 36 (1): 65–6. PMID 11211215.
- ↑ Kelly PM, Poon FW (2001). "Hepatic tumours in glycogen storage disease type 1 (von Gierke's disease)". Clin Radiol. 56 (6): 505–8. doi:10.1053/crad.2000.0457. PMID 11428803.
- ↑ Lee PJ (2002). "Glycogen storage disease type I: pathophysiology of liver adenomas". Eur J Pediatr. 161 Suppl 1: S46–9. doi:10.1007/s00431-002-1002-0. PMID 12373570.
- ↑ Reitsma-Bierens WC (1993). "Renal complications in glycogen storage disease type I." Eur J Pediatr. 152 Suppl 1: S60–2. PMID 8319728.
- ↑ Reitsma-Bierens WC, Smit GP, Troelstra JA (1992). "Renal function and kidney size in glycogen storage disease type I." Pediatr Nephrol. 6 (3): 236–8. PMID 1616830.
- ↑ Chen YT, Coleman RA, Scheinman JI, Kolbeck PC, Sidbury JB (1988). "Renal disease in type I glycogen storage disease". N Engl J Med. 318 (1): 7–11. doi:10.1056/NEJM198801073180102. PMID 3422104.
- ↑ Weinstein DA, Somers MJ, Wolfsdorf JI (2001). "Decreased urinary citrate excretion in type 1a glycogen storage disease". J Pediatr. 138 (3): 378–82. doi:10.1067/mpd.2001.111322. PMID 11241046.
- ↑ Lee PJ, Dalton RN, Shah V, Hindmarsh PC, Leonard JV (1995). "Glomerular and tubular function in glycogen storage disease". Pediatr Nephrol. 9 (6): 705–10. PMID 8747109.
- ↑ Restaino I, Kaplan BS, Stanley C, Baker L (1993). "Nephrolithiasis, hypocitraturia, and a distal renal tubular acidification defect in type 1 glycogen storage disease". J Pediatr. 122 (3): 392–6. PMID 8441093.
- ↑ Wang DQ, Carreras CT, Fiske LM, Austin S, Boree D, Kishnani PS; et al. (2012). "Characterization and pathogenesis of anemia in glycogen storage disease type Ia and Ib". Genet Med. 14 (9): 795–9. doi:10.1038/gim.2012.41. PMC 3808879. PMID 22678084.
- ↑ Weinstein DA, Roy CN, Fleming MD, Loda MF, Wolfsdorf JI, Andrews NC (2002). "Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease". Blood. 100 (10): 3776–81. doi:10.1182/blood-2002-04-1260. PMID 12393428.
- ↑ Czapek EE, Deykin D, Salzman EW (1973). "Platelet dysfunction in glycogen storage disease type I." Blood. 41 (2): 235–47. PMID 4350560.
- ↑ Corby DG, Putnam CW, Greene HL (1974). "Impaired platelet function in glucose-6-phosphatase deficiency". J Pediatr. 85 (1): 71–6. PMID 4212074.
- ↑ Hutton RA, Macnab AJ, Rivers RP (1976). "Defect of platelet function associated with chronic hypoglycaemia". Arch Dis Child. 51 (1): 49–55. PMC 1545862. PMID 942229.
- ↑ Visser G, Rake JP, Labrune P, Leonard JV, Moses S, Ullrich K; et al. (2002). "Granulocyte colony-stimulating factor in glycogen storage disease type 1b. Results of the European Study on Glycogen Storage Disease Type 1". Eur J Pediatr. 161 Suppl 1: S83–7. doi:10.1007/s00431-002-1010-0. PMID 12373578.
- ↑ Chou JY, Jun HS, Mansfield BC (2010). "Neutropenia in type Ib glycogen storage disease". Curr Opin Hematol. 17 (1): 36–42. doi:10.1097/MOH.0b013e328331df85. PMC 3099242. PMID 19741523.
- ↑ Franceschini R, Gianetta E, Pastorino A, Dallegri F, Cataldi A, Corsini G; et al. (1996). "Crohn's-like colitis in glycogen storage disease Ib: a case report". Hepatogastroenterology. 43 (12): 1461–4. PMID 8975948.
- ↑ Dieckgraefe BK, Korzenik JR, Husain A, Dieruf L (2002). "Association of glycogen storage disease 1b and Crohn disease: results of a North American survey". Eur J Pediatr. 161 Suppl 1: S88–92. doi:10.1007/s00431-002-1011-z. PMID 12373579.
- ↑ Kilpatrick L, Garty BZ, Lundquist KF, Hunter K, Stanley CA, Baker L; et al. (1990). "Impaired metabolic function and signaling defects in phagocytic cells in glycogen storage disease type 1b". J Clin Invest. 86 (1): 196–202. doi:10.1172/JCI114684. PMC 296707. PMID 2164043.
- ↑ Mansfield BC (1999). "Molecular Genetics of Type 1 Glycogen Storage Diseases". Trends Endocrinol Metab. 10 (3): 104–113. PMID 10322403.
- ↑ Veiga-da-Cunha M, Gerin I, Chen YT, de Barsy T, de Lonlay P, Dionisi-Vici C; et al. (1998). "A gene on chromosome 11q23 coding for a putative glucose- 6-phosphate translocase is mutated in glycogen-storage disease types Ib and Ic". Am J Hum Genet. 63 (4): 976–83. doi:10.1086/302068. PMC 1377500. PMID 9758626.
- ↑ Froissart R, Piraud M, Boudjemline AM, Vianey-Saban C, Petit F, Hubert-Buron A; et al. (2011). "Glucose-6-phosphatase deficiency". Orphanet J Rare Dis. 6: 27. doi:10.1186/1750-1172-6-27. PMC 3118311. PMID 21599942.
- ↑ Ozen H (2007). "Glycogen storage diseases: new perspectives". World J Gastroenterol. 13 (18): 2541–53. PMC 4146814. PMID 17552001.
- ↑ Bali DS, Chen YT, Austin S, et al. Glycogen Storage Disease Type I. 2006 Apr 19 [Updated 2016 Aug 25]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1312/