Abderhalden-Kaufmann-Lignac syndrome: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
 
(118 intermediate revisions by 3 users not shown)
Line 3: Line 3:
{{CMG}}; {{AE}}{{Abdulkerim}}
{{CMG}}; {{AE}}{{Abdulkerim}}


{{SK}} Abderhalden-Lignac-Kaufmann disease; nephropathic cystinosis
{{SK}} [[Abderhalden-Lignac-Kaufmann disease]]; [[nephropathic cystinosis]]
 
[[Image:autorecessive.svg|thumb|right|Abderhalden-Kaufmann-Lignac syndrome has an autosomal recessive pattern of inheritance.]]


==Overview==
==Overview==
'''Abderhalden-Kaufmann-Lignac syndrome''', also called '''Abderhalden-Lignac-Kaufmann disease''' or '''nephropathic cystinosis''', is an [[autosomal recessive]] renal disorder of childhood comprising [[cystinosis]] and renal [[rickets]].
'''[[Abderhalden-Kaufmann-Lignac syndrome]]''', also called '''[[Abderhalden-Lignac-Kaufmann disease]]''' or '''[[nephropathic cystinosis]]''', is an [[autosomal recessive]] renal [[disorder]] of [[childhood]] comprising [[cystinosis]] and [[renal]] [[rickets]]. It is caused by [[mutation]] in the CTNS [[gene]] [[encoding]] for [[cystinosin]], transporting [[cystine]] out of the [[lysosomes]]. A [[defect]] in the [[cystinosin]] leads to [[accumulation]] of [[excessive]] [[cystine]] [[crystals]] in the [[lsysosomes]] of all [[body]] [[cells]] and [[organs]]. The most commonly affected [[organs]] are the [[eyes]] and [[kidneys]] but it can also affect the [[thyroid]], [[pancreas]], [[gonads]], [[muscles]] and [[CNS]]. The [[symptoms]] are [[renal]] [[calculi]], [[osteomalacia]], [[aminoaciduria]], [[glycosuria]], [[polyuria]], [[chronic]] [[acidosis]], [[hypophosphatemia]] with [[vitamin D]]-[[resistant]] [[rickets]], and often with [[hypokalemia]], [[photophobia]], [[blepharospasm]],  [[hypothyroidism]], [[primary]] [[hypogonadism]] in [[males]], [[hypotonia]], [[speech]] [[delay]], [[motor]] [[impairment]], [[cognitive]] [[dysfunction]], [[Diabetes]], [[hypopigmentation]], coarsened [[facial]] features and impaired [[sweating]]. The [[diagnosis]] is made with measuring [[cystine]] levels in [[polymorphonuclear]] [[leukocytes]] or cultured [[fibroblasts]]. [[Molecular]] [[analysis]] of the cystinosin [[gene]] can be done for [[definitive]] [[diagnosis]].The [[mainstay]] of [[treatment]] is [[cystine]]-[[depleting]] [[therapy]] with [[cysteamine]]. There are no established measures for the [[primary]] or [[secondary]] prevention of Abderhalden-Kaufmann-Lignac [[syndrome]].


==Historical Perspective==
==Historical Perspective==
 
Abderhalden-Kaufmann-Lignac [[syndrome]] was first described by [[Emil Abderhalden]], Swiss biochemist in 1903 as the [[familial]] [[cystine]] accumulation [[disease]]. Abderhalden referred to a [[child]] initially encountered by [[Eduard Kaufmann]], a German physician. [[George Lignac]], a Dutch pathologist, was the first to give more detailed [[systematic]] description of the [[disease]] and to associate [[cystinosis]] with its major [[clinical]] manifestations such as [[rickets]], [[renal disease]] and [[growth]] [[retardation]]. The [[disease]] is named for [[Emil Abderhalden]], [[Eduard Kaufmann]] and [[George Lignac]].<ref name="pmid12110740">{{cite journal| author=Gahl WA, Thoene JG, Schneider JA| title=Cystinosis. | journal=N Engl J Med | year= 2002 | volume= 347 | issue= 2 | pages= 111-21 | pmid=12110740 | doi=10.1056/NEJMra020552 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12110740  }} </ref>
Abderhalden-Kaufmann=Lignac syndrome was first discovered by Emil Abderhalden (1877-1950), a swiss biochemist and physiologist, Eduard Kaufmann (1860-1931), a German physician and George Otto Emil Lignac (1891-1954), a Dutch Pathologist-Anatomist.


==Classification==
==Classification==


Abderhalden-Kaufmann-Lignac syndrome may be classified according to age of onset into three types:
Abderhalden-Kaufmann-Lignac [[syndrome]] may be classified according to [[age]] of [[onset]] into three types<ref name="pmid25165189">{{cite journal| author=Emma F, Nesterova G, Langman C, Labbé A, Cherqui S, Goodyer P | display-authors=etal| title=Nephropathic cystinosis: an international consensus document. | journal=Nephrol Dial Transplant | year= 2014 | volume= 29 Suppl 4 | issue=  | pages= iv87-94 | pmid=25165189 | doi=10.1093/ndt/gfu090 | pmc=4158338 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25165189  }} </ref>:
*'''Infantile Nephropathic Cystinosis''' (95%): onset on early infancy.The most severe clinical form of cystinosis, commonly present with renal Fanconi syndrome by 6-12 months of age, and without specific treatment, almost all will develop end-stage renal disease and without specific treatment, almost all will develop end-stage renal disease (ESRD) by 10-12 years of age .
*'''Juvenile''' (5%): onset on adolescent.
*'''Non-nephropathic'''(case report): onset on adulthood.
==Pathophysiology==


It is thought that Abderhalden-Kaufmann-Lignac syndrome is the result of CTNS gene mutation which encodes for cystinosin, a transporter protein which carries cystine from lysosomes to cytosol.A defect in the CTNS gene leads to a high level of cystine accumulation in the lysosome. It is transmitted in autosomal recessive pattern, where inheritance of one defective gene from each parents who are carrrier, put at risk of their 25% of children manifest the disease. The exact pathophysiology of the disease is still not properly understood but there are suggested mechanisms:
*'''Infantile Nephropathic Cystinosis''' (95%): onset in early [[infancy]]. The most [[severe]] clinical form of [[cystinosis]], commonly present with [[renal]] [[Fanconi]] [[syndrome]] by 6-12 months of [[age]], and without specific [[treatment]], almost all will develop [[end-stage renal disease]] and without specific [[treatment]], almost all will develop end-stage renal [[disease]] (ESRD) by 10-12 years of age .
*#1 Increased cystine levels in the lysosome links to enhanced apoptosis.
*'''Juvenile''' (5%): onset in [[adolescence]].
**#2 lysosomal cystine accumulation leads to cellular ATP depletion.  
*'''Non-nephropathic'''(case report): onset in [[adulthood]]. [[Corneal]] involvement with [[renal]] sparing.


==Causes==
==Pathophysiology==
Disease name] may be caused by [cause1], [cause2], or [cause3].


OR
It is thought that Abderhalden-Kaufmann-Lignac [[syndrome]] is the result of CTNS [[gene]] [[mutation]] which encodes for [[cystinosin]], a transporter [[protein]] which carries [[cystine]] from [[lysosomes]] to [[cytosol]]. A [[defect]] in the CTNS [[gene]] leads to a high level of [[cystine]] accumulation in the [[lysosome]]. It is transmitted in [[autosomal]] [[recessive]] pattern, where [[inheritance]] of one [[defective]] [[gene]] from each [[parents]] who are [[carrrier]], put at [[risk]] of their 25% of [[children]] [[manifest]] the [[disease]]. The exact [[pathophysiology]] of the disease is still not properly understood but there are suggested [[mechanismsm]].<ref name="pmid12444206">{{cite journal| author=Park M, Helip-Wooley A, Thoene J| title=Lysosomal cystine [[storage]] augments [[apoptosis]] in [[cultured]] human [[fibroblasts]] and [[renal]] [[tubular]] [[epithelial]] cells. | journal=J Am Soc Nephrol | year= 2002 | volume= 13 | issue= 12 | pages= 2878-87 | pmid=12444206 | doi=10.1097/01.asn.0000036867.49866.59 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12444206  }} </ref><ref name="pmid19959713">{{cite journal| author=Sansanwal P, Yen B, Gahl WA, Ma Y, Ying L, Wong LJ | display-authors=etal| title=Mitochondrial autophagy promotes cellular injury in nephropathic cystinosis. | journal=J Am Soc Nephrol | year= 2010 | volume= 21 | issue= 2 | pages= 272-83 | pmid=19959713 | doi=10.1681/ASN.2009040383 | pmc=2834547 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19959713  }} </ref>


Common causes of [disease] include [cause1], [cause2], and [cause3].
#Increased [[cystine]] levels in the [[lysosome]] links to enhanced [[apoptosis]].
#lysosomal [[cystine]] [[accumulation]] leads to [[cellular]] [[ATP]] [[depletion]].


OR
==Causes==
 
The most common cause of [disease name] is [cause 1]. Less common causes of [disease name] include [cause 2], [cause 3], and [cause 4].
 
OR
 
The cause of [disease name] has not been identified. To review risk factors for the development of [disease name], click [[Pericarditis causes#Overview|here]].
 
==Differentiating ((Page name)) from other Diseases==
[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].


OR
The cause of Abderhalden-Kaufmann-Lignac [[syndrome]] is CTNS [[gene]] mutation in the [[lysosomal]] [[membrane]] [[trafficking]] [[protein]] called [[cystinosin]], which causes to [[cystine]] accumulation in the [[lysosome]] of all body [[cells]] and [[organs]], leads to [[apoptosis]] and [[cellular]] [[ATP]] depletion.It is a rare [[autosomal]] [[recessive]] [[lysosomal storage diseases]].<ref name="pmid27102039">{{cite journal| author=Elmonem MA, Veys KR, Soliman NA, van Dyck M, van den Heuvel LP, Levtchenko E| title=Cystinosis: a review. | journal=Orphanet J Rare Dis | year= 2016 | volume= 11 | issue=  | pages= 47 | pmid=27102039 | doi=10.1186/s13023-016-0426-y | pmc=4841061 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27102039  }} </ref>


[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].
==Differentiating Abderhalden-Kaufmann-Lignac syndrome from other Diseases==
Abderhalden-Kaufmann-Lignac [[syndrome]] must be differentiated from other [[diseases]] that cause [[renal]] [[Fanconi]] [[syndrome]], [[photophobia]], [[blepharospasm]] , and [[rickets]] or [[osteomalacia]], such as [[Lowe syndrome]], [[Dent disease]]; [[Idiopathic]] [[fanconi]] [[syndrome]].<ref name="pmid12110740">{{cite journal| author=Gahl WA, Thoene JG, Schneider JA| title=Cystinosis. | journal=N Engl J Med | year= 2002 | volume= 347 | issue= 2 | pages= 111-21 | pmid=12110740 | doi=10.1056/NEJMra020552 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12110740  }} </ref>


==Epidemiology and Demographics==
==Epidemiology and Demographics==
The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.
OR
In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.
OR
In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate of [number range]%.
Patients of all age groups may develop [disease name].
OR
The incidence of [disease name] increases with age; the median age at diagnosis is [#] years.
OR
[Disease name] commonly affects individuals younger than/older than [number of years] years of age.
OR
[Chronic disease name] is usually first diagnosed among [age group].
OR
[Acute disease name] commonly affects [age group].
There is no racial predilection to [disease name].
OR
[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].
[Disease name] affects men and women equally.


OR
*The [[incidence]] of Abderhalden-Kaufmann-Lignac [[syndrome]] is [[approximately]] 1 per 100,000 to 200,000 live [[births]] [[worldwide]].


[Gender 1] are more commonly affected by [disease name] than [gender 2]. The [gender 1] to [gender 2] ratio is approximately [number > 1] to 1.
*Patients of all [[age]] groups may [[develop]] Abderhalden-Kaufmann-Lignac [[syndrome]].
*Abderhalden-Kaufmann-Lignac [[syndrome]] commonly affects [[infants]].


*End [[Stage]] [[Renal]] [[Disease]] is usually first diagnosed among 10-12 years of [[age]] with out proper [[treatment]].<ref name="pmid20803298">{{cite journal| author=Greco M, Brugnara M, Zaffanello M, Taranta A, Pastore A, Emma F| title=Long-term outcome of nephropathic cystinosis: a 20-year single-center experience. | journal=Pediatr Nephrol | year= 2010 | volume= 25 | issue= 12 | pages= 2459-67 | pmid=20803298 | doi=10.1007/s00467-010-1641-8 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20803298  }} </ref>


*There is no [[racial]] predilection to Abderhalden-Kaufmann-Lignac [[syndrome]].


The majority of [disease name] cases are reported in [geographical region].
*Male are more commonly [[affected]] by Abderhalden-Kaufmann-Lignac [[syndrome]] than [[female]]. The male to female [[ratio]] is approximately 1.5 to 1.


OR
*Although a wide geographic [[variability]] has been reported, The majority of Abderhalden-Kaufmann-Lignac [[syndrome]] cases are reported in [[France]] and [[Canada]]. eg, [[incidence]] of 1:26,000 in [[Brittany]], [[France]] and 1:62,500 in parts of [[Quebec]], [[Canada]].


[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].
*Abderhalden-Kaufmann-Lignac [[syndrome]] is a rare [[disease]] that tends to affect [[infants]] and [[adolescent]].<ref name="pmid12110740">{{cite journal| author=Gahl WA, Thoene JG, Schneider JA| title=Cystinosis. | journal=N Engl J Med | year= 2002 | volume= 347 | issue= 2 | pages= 111-21 | pmid=12110740 | doi=10.1056/NEJMra020552 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12110740  }} </ref>


==Risk Factors==
==Risk Factors==
There are no established risk factors for [disease name].
There are no established risk factors for Abderhalden-Kaufmann-Lignac syndrome.
 
OR
 
The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].
 
OR
 
Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
 
OR
 
Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.


==Screening==
==Screening==
There is insufficient evidence to recommend routine screening for [disease/malignancy].
There is insufficient evidence to recommend routine screening for Abderhalden-Kaufmann-Lignac syndrome.
 
OR
 
According to the [guideline name], screening for [disease name] is not recommended.
 
OR
 
According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].


==Natural History, Complications, and Prognosis==
==Natural History, Complications, and Prognosis==
If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
If left untreated, Abderhalden-Kaufmann-Lignac [[syndrome]] may progress to develop [[chronic]] [[renal]] [[failure]] and [[extrarenal]] [[complications]] such as [[dwarfism]], [[rickets]], [[hyphothyroidism]], [[hypogonadism]], [[hypopigmentation]], diabetes, distal vacuolar myopathy, [[osteoporosis]], blindness, CNS complications such as [[Hypotonia]], [[speech delay]], [[neurocognitive]] [[dysfunction]], and [[encephalopathy]].<ref name="pmid3307383">{{cite journal| author=Fivush B, Green OC, Porter CC, Balfe JW, O'Regan S, Gahl WA| title=Pancreatic endocrine insufficiency in posttransplant cystinosis. | journal=Am J Dis Child | year= 1987 | volume= 141 | issue= 10 | pages= 1087-9 | pmid=3307383 | doi=10.1001/archpedi.1987.04460100065027 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3307383  }} </ref><ref name="pmid2712751">{{cite journal| author=Fink JK, Brouwers P, Barton N, Malekzadeh MH, Sato S, Hill S | display-authors=etal| title=Neurologic complications in long-standing nephropathic cystinosis. | journal=Arch Neurol | year= 1989 | volume= 46 | issue= 5 | pages= 543-8 | pmid=2712751 | doi=10.1001/archneur.1989.00520410077027 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2712751  }} </ref>
 
OR
 
Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
 
OR


Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.
[[Prognosis]] of Abderhalden-Kaufmann-Lignac [[syndrome]] depends on early [[diagnosis]], and prompt starting and good [[compliance]] with [[cysteamine]] [[treatment]]. [[life]] [[expectancy]] can extend past 50 years.<ref name="pmid27102039">{{cite journal| author=Elmonem MA, Veys KR, Soliman NA, van Dyck M, van den Heuvel LP, Levtchenko E| title=Cystinosis: a review. | journal=Orphanet J Rare Dis | year= 2016 | volume= 11 | issue=  | pages= 47 | pmid=27102039 | doi=10.1186/s13023-016-0426-y | pmc=4841061 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27102039  }} </ref>


==Diagnosis==
==Diagnosis==
===Diagnostic Study of Choice===
The diagnosis of Abderhalden-Kaufmann-Lignac [[syndrome]] is made with [[clinical]] and [[laboratory]] findings. The [[diagnosis]] is confirmed by [[molecular]] [[analysis]] of the [[cystinosin]] [[gene]].<ref name="pmid12110740">{{cite journal| author=Gahl WA, Thoene JG, Schneider JA| title=Cystinosis. | journal=N Engl J Med | year= 2002 | volume= 347 | issue= 2 | pages= 111-21 | pmid=12110740 | doi=10.1056/NEJMra020552 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12110740  }} </ref>
The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].
 
OR
 
The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].
 
OR
 
The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].
 
OR
 
There are no established criteria for the diagnosis of [disease name].


===History and Symptoms===
===History and Symptoms===
The majority of patients with [disease name] are asymptomatic.
OR


The hallmark of [disease name] is [finding]. A positive history of [finding 1] and [finding 2] is suggestive of [disease name]. The most common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3]. Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3]. Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].
The [[hallmark]] of Abderhalden-Kaufmann-Lignac [[syndrome]] is early [[corneal]] [[cystine]] [[crystal]] deposition. The most common symptoms of Abderhalden-Kaufmann-Lignac syndrome include renal fanconi syndrome, [[dwarfism]], and [[rickets]]. Other presenting [[symptoms]] of Abderhalden-Kaufmann-Lignac [[syndrome]] include [[photophobia]], [[blepharospasm]], [[aminoaciduria]], [[glycosuria]], [[hypokalemia]], [[vomiting]], [[feeding]] [[difficulties]], [[decreased]] [[appetite]], [[nephrolithiasis]], [[nephrocalcinosis]], [[distal]] [[muscle]] [[wasting]] and [[weakness]], [[hypothyroidism]], [[hypogonadism]], [[hypopigmentation]], [[diabetes]].<ref name="pmid29905968">{{cite journal| author=Florenzano P, Ferreira C, Nesterova G, Roberts MS, Tella SH, de Castro LF | display-authors=etal| title=Skeletal Consequences of Nephropathic Cystinosis. | journal=J Bone Miner Res | year= 2018 | volume= 33 | issue= 10 | pages= 1870-1880 | pmid=29905968 | doi=10.1002/jbmr.3522 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29905968  }} </ref><ref name="pmid29260317">{{cite journal| author=Ariceta G, Giordano V, Santos F| title=Effects of [[long-term]] [[cysteamine]] [[treatment]] in patients with [[cystinosis]]. | journal=Pediatr Nephrol | year= 2019 | volume= 34 | issue= 4 | pages= 571-578 | pmid=29260317 | doi=10.1007/s00467-017-3856-4 | pmc=6394685 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29260317  }} </ref>


===Physical Examination===
===Physical Examination===
Patients with [disease name] usually appear [general appearance]. Physical examination of patients with [disease name] is usually remarkable for [finding 1], [finding 2], and [finding 3].
The presence of [[cystine]] [[crystal]] in the [[cornea]], [[growth failure]], [[short]] [[stature]], and [[knock]]-[[knees]] ([[valgus]] [[deformity]]) on [[physical]] [[examination]] is highly suggestive of Abderhalden-Kaufmann-Lignac [[syndrome]].<ref name="pmid12110740">{{cite journal| author=Gahl WA, Thoene JG, Schneider JA| title=Cystinosis. | journal=N Engl J Med | year= 2002 | volume= 347 | issue= 2 | pages= 111-21 | pmid=12110740 | doi=10.1056/NEJMra020552 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12110740  }} </ref>
 
OR
 
Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
The presence of [finding(s)] on physical examination is diagnostic of [disease name].
 
OR
 
The presence of [finding(s)] on physical examination is highly suggestive of [disease name].


===Laboratory Findings===
===Laboratory Findings===
An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].
An elevated [[Cystine]] [[concentrations]] 5-10 nmol half-cystine/mg [[cell]] [[protein]] in individuals who are [[homozygous]] for Abderhalden-Kaufmann-Lignac [[syndrome]] is other [[diagnostic]] finding.Reference [[range]] levels are below 0.2 nmol half-cystine/mg [[cell]] [[protein]]. When a [[fetus]] is at [[risk]] for Abderhalden-Kaufmann-Lignac [[syndrome]], the [[cystine]] level can be measured in [[chorionic]] [[villi]] or [[cultured]] [[amniotic]] [[fluid]] [[cells]].
 
[[Laboratory]] findings [[consistent]] with the [[diagnosis]] of Abderhalden-Kaufmann-Lignac [[syndrome]] include [[serum]] [[electrolyte]] [[abnormalities]] such as [[hypokalemia]], [[hypophosphatemia]], [[hypocalcemia]], [[low]] [[bicarbonate]] [[levels]], [[hyponatremia]], [[ABG]] to detect [[metabolic]] [[acidosis]], and [[urine]] [[test]] for [[glycosuria]], [[aminoaciduria]], [[proteinuria]].<ref name="pmid12110740">{{cite journal| author=Gahl WA, Thoene JG, Schneider JA| title=Cystinosis. | journal=N Engl J Med | year= 2002 | volume= 347 | issue= 2 | pages= 111-21 | pmid=12110740 | doi=10.1056/NEJMra020552 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12110740  }} </ref>
OR
 
Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
 
OR
 
[Test] is usually normal among patients with [disease name].
 
OR
 
Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].
 
OR
 
There are no diagnostic laboratory findings associated with [disease name].


===Electrocardiogram===
===Electrocardiogram===
There are no ECG findings associated with [disease name].
There are no ECG findings associated with Abderhalden-Kaufmann-Lignac syndrome.
 
OR
 
An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].


===X-ray===
===X-ray===
There are no x-ray findings associated with [disease name].
There are no specific [[x-ray]] findings [[associated]] with Abderhalden-Kaufmann-Lignac [[syndrome]]. However, an [[x-ray]] may be helpful in the [[diagnosis]] of [[complications]] of Abderhalden-Kaufmann-Lignac [[syndrome]], which includes [[osteoporosis]], [[urinary]] [[tract]] [[calcifications]] and [[rickets]]<ref name="pmid29905968">{{cite journal| author=Florenzano P, Ferreira C, Nesterova G, Roberts MS, Tella SH, de Castro LF | display-authors=etal| title=Skeletal Consequences of Nephropathic Cystinosis. | journal=J Bone Miner Res | year= 2018 | volume= 33 | issue= 10 | pages= 1870-1880 | pmid=29905968 | doi=10.1002/jbmr.3522 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29905968  }} </ref>.
 
OR
 
An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].


===Echocardiography or Ultrasound===
===Echocardiography or Ultrasound===
There are no echocardiography/ultrasound  findings associated with [disease name].
There are no specific [[echocardiography]] findings associated with Abderhalden-Kaufmann-Lignac [[syndrome]]. However, an [[echocardiography]] may be helpful in the diagnosis of [[Left]] [[ventricular]] hypertrabeculation/non-compaction (LVHT) associated with [[accumulation]] of [[cystine]] in the [[cardiac]] muscles.<ref name="pmid11711464">{{cite journal| author=Jenni R, Oechslin E, Schneider J, Attenhofer Jost C, Kaufmann PA| title=Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy. | journal=Heart | year= 2001 | volume= 86 | issue= 6 | pages= 666-71 | pmid=11711464 | doi=10.1136/heart.86.6.666 | pmc=1730012 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11711464  }} </ref>
 
There are no specific [[ultrasound]] findings associated with Abderhalden-Kaufmann-Lignac [[syndrome]]. However, an [[ultrasound]] may be helpful in the [[diagnosis]] of [[complications]] of Abderhalden-Kaufmann-Lignac [[syndrome]], which include [[nephrolithiasis]], and [[renal]] [[medullary]] [[nephrocalcinosis]].<ref name="pmid29905968">{{cite journal| author=Florenzano P, Ferreira C, Nesterova G, Roberts MS, Tella SH, de Castro LF | display-authors=etal| title=Skeletal Consequences of Nephropathic Cystinosis. | journal=J Bone Miner Res | year= 2018 | volume= 33 | issue= 10 | pages= 1870-1880 | pmid=29905968 | doi=10.1002/jbmr.3522 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29905968  }} </ref>
OR
 
Echocardiography/ultrasound  may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no echocardiography/ultrasound findings associated with [disease name]. However, an echocardiography/ultrasound may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].


===CT scan===
===CT scan===
There are no CT scan findings associated with [disease name].
There are no specific [[CT]] [[scan]] findings associated with Abderhalden-Kaufmann-Lignac [[syndrome]]. However, a [[CT]] [[scan]] may be helpful in the [[diagnosis]] of [[complications]] of Abderhalden-Kaufmann-Lignac [[syndrome]], which include isolated [[ventricular]] [[non-compaction]] [[Central]] [[nervous]] [[system]] [[abnormalities]], [[nephrolithiasis]], [[papilledema]] and renal medullary [[nephrocalcinosis]].<ref name="pmid17068279">{{cite journal| author=Stöllberger C, Finsterer J| title=Pitfalls in the diagnosis of left ventricular [[hypertrabeculation/non-compaction]]. | journal=Postgrad Med J | year= 2006 | volume= 82 | issue= 972 | pages= 679-83 | pmid=17068279 | doi=10.1136/pgmj.2006.046169 | pmc=2653912 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17068279  }} </ref><ref name="pmid19427638">{{cite journal| author=Bava S, Theilmann RJ, Sach M, May SJ, Frank LR, Hesselink JR | display-authors=etal| title=Developmental changes in cerebral white matter [[microstructure]] in a disorder of lysosomal storage. | journal=Cortex | year= 2010 | volume= 46 | issue= 2 | pages= 206-16 | pmid=19427638 | doi=10.1016/j.cortex.2009.03.008 | pmc=3351112 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19427638  }} </ref>
 
OR
 
[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].


===MRI===
===MRI===
There are no MRI findings associated with [disease name].
There are no specific [[MRI]] findings associated with Abderhalden-Kaufmann-Lignac [[syndrome]]. However, a MRI may be helpful in the [[diagnosis]] of [[complications]] of Abderhalden-Kaufmann-Lignac [[syndrome]], which include [[Central]] [[nervous]] [[system abnormalities]], [[rickets]], [[papilledema]], and [[osteoporosis]]. [[cognitive]] [[dysfunction]] could be related to [[abnormalities]] in the [[cerebral]] [[white matter]] [[microstructure]] and has been demonstrated using in [[magnetic resonance]] diffusion tensor imaging.<ref name="pmid19427638">{{cite journal| author=Bava S, Theilmann RJ, Sach M, May SJ, Frank LR, Hesselink JR | display-authors=etal| title=Developmental changes in cerebral white matter microstructure in a disorder of lysosomal storage. | journal=Cortex | year= 2010 | volume= 46 | issue= 2 | pages= 206-16 | pmid=19427638 | doi=10.1016/j.cortex.2009.03.008 | pmc=3351112 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19427638  }} </ref>
 
OR
 
[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].


===Other Imaging Findings===
===Other Imaging Findings===
There are no other imaging findings associated with [disease name].
other imaging findings associated with Abderhalden-Kaufmann-Lignac [[syndrome]] is [[decreased]] [[bone]] [[mass]] evaluated by [[Bone density scan]]<ref name="pmid29905968">{{cite journal| author=Florenzano P, Ferreira C, Nesterova G, Roberts MS, Tella SH, de Castro LF | display-authors=etal| title=Skeletal Consequences of Nephropathic Cystinosis. | journal=J Bone Miner Res | year= 2018 | volume= 33 | issue= 10 | pages= 1870-1880 | pmid=29905968 | doi=10.1002/jbmr.3522 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29905968  }} </ref>.
 
OR
 
[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].


===Other Diagnostic Studies===
===Other Diagnostic Studies===
There are no other diagnostic studies associated with [disease name].
Other [[diagnostic]] studies for Abderhalden-Kaufmann-Lignac [[syndrome]] include [[slit-lamp]] examination, which demonstrates [[cystine]] [[crystals]] [[deposition]] in the [[cornea]]<ref name="pmid25165189">{{cite journal| author=Emma F, Nesterova G, Langman C, Labbé A, Cherqui S, Goodyer P | display-authors=etal| title=Nephropathic cystinosis: an international consensus document. | journal=Nephrol Dial Transplant | year= 2014 | volume= 29 Suppl 4 | issue=  | pages= iv87-94 | pmid=25165189 | doi=10.1093/ndt/gfu090 | pmc=4158338 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25165189  }} </ref>.
 
OR
 
[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].


==Treatment==
==Treatment==
===Medical Therapy===
===Medical Therapy===
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
Symptomatic treatments:
 
OR
 
Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
 
OR
 
The majority of cases of [disease name] are self-limited and require only supportive care.
 
OR
 
[Disease name] is a medical emergency and requires prompt treatment.
 
OR
 
The mainstay of treatment for [disease name] is [therapy].
 
OR
 
The optimal therapy for [malignancy name] depends on the stage at diagnosis.
 
OR
 
[Therapy] is recommended among all patients who develop [disease name].
 
OR
 
Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
 
OR
 
Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
 
OR
 
Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].


OR
*Rehydration
*High [[dosage]] of [[vitamin D]]
*Electrolyte [[Supplements]]- [[Sodium]] [[citrate]] to treat [[metabolic acidosis]]
*Electrolyte [[Replacement]]- [[Potassium]], [[bicarbonate]] and [[phosphate]] abnormalities treated with [[oral]] or [[intravenous]] supplements.


Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
The [[mainstay]] of [[treatment]] for Abderhalden-Kaufmann-Lignac [[syndrome]] is [[cysteamine]]. It is available in two [[formulations]]; [[tablet]] and [[eyedrops]]. [[cysteamine]], facilitates [[lysosomal]] [[cystine]] clearance and delays progression to [[ESRD]], significantly improves [[growth]], decreases the [[frequency]] and severity of [[extrarenal]] [[complications]], and is associated with extended [[life]] [[expectancy]]; however, no [[curative]] [[treatment]] is yet available.<ref name="pmid12110740">{{cite journal| author=Gahl WA, Thoene JG, Schneider JA| title=Cystinosis. | journal=N Engl J Med | year= 2002 | volume= 347 | issue= 2 | pages= 111-21 | pmid=12110740 | doi=10.1056/NEJMra020552 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12110740  }} </ref>


===Surgery===
===Surgery===
Surgical intervention is not recommended for the management of [disease name].
The [[mainstay]] of [[treatment]] for Abderhalden-Kaufmann-Lignac [[syndrome]] is [[medical]] [[therapy]]. [[Surgery]] is may be needed for [[patients]] with [[complications]] of Abderhalden-Kaufmann-Lignac [[syndrome]] such as [[End]] [[Stage]] [[Renal]] [[Disease]] or [[nephrolithiasis]].<ref name="pmid22903658">{{cite journal| author=Nesterova G, Gahl WA| title=Cystinosis: the evolution of a treatable disease. | journal=Pediatr Nephrol | year= 2013 | volume= 28 | issue= 1 | pages= 51-9 | pmid=22903658 | doi=10.1007/s00467-012-2242-5 | pmc=3505515 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22903658  }} </ref><ref name="pmid29260317">{{cite journal| author=Ariceta G, Giordano V, Santos F| title=Effects of long-term cysteamine treatment in patients with cystinosis. | journal=Pediatr Nephrol | year= 2019 | volume= 34 | issue= 4 | pages= 571-578 | pmid=29260317 | doi=10.1007/s00467-017-3856-4 | pmc=6394685 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29260317  }} </ref>
 
OR
 
Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]
 
OR
 
The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].
 
OR
 
The feasibility of surgery depends on the stage of [malignancy] at diagnosis.
 
OR
 
Surgery is the mainstay of treatment for [disease or malignancy].


===Primary Prevention===
===Primary Prevention===
There are no established measures for the primary prevention of [disease name].
There are no [[established]] [[measures]] for the [[primary]] [[prevention]] of Abderhalden-Kaufmann-Lignac [[syndrome]]<ref name="pmid12110740">{{cite journal| author=Gahl WA, Thoene JG, Schneider JA| title=Cystinosis. | journal=N Engl J Med | year= 2002 | volume= 347 | issue= 2 | pages= 111-21 | pmid=12110740 | doi=10.1056/NEJMra020552 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12110740  }} </ref>.
 
OR
 
There are no available vaccines against [disease name].
 
OR
 
Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
 
OR
 
[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].


===Secondary Prevention===
===Secondary Prevention===
There are no established measures for the secondary prevention of [disease name].
There are no [[established]] [[measures]] for the [[secondary]] [[prevention]] of Abderhalden-Kaufmann-Lignac [[syndrome]]<ref name="pmid12110740">{{cite journal| author=Gahl WA, Thoene JG, Schneider JA| title=Cystinosis. | journal=N Engl J Med | year= 2002 | volume= 347 | issue= 2 | pages= 111-21 | pmid=12110740 | doi=10.1056/NEJMra020552 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12110740  }} </ref>.
 
OR
 
Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].


==Related Chapters==


==Related Chapters==
*[[Cystinosin]]
* [[Cystinosin]]


==References==
==References==
{{reflist|2}}
{{reflist|2}}


[[Category:Genetic disorders]]
[[Category:Genetic disorders]]
[[Category:Autosomal recessive disorders]]
[[Category:Autosomal recessive disorders]]
[[Category:Kidney diseases]]
[[Category:Kidney diseases]]
[[Category:Up To Date]]


[[pt:Síndrome de Abderhalden-Kaufmann-Lignac]]
[[pt:Síndrome de Abderhalden-Kaufmann-Lignac]]
Line 368: Line 133:
{{WH}}
{{WH}}
{{WS}}
{{WS}}
<references />

Latest revision as of 15:37, 12 November 2021

WikiDoc Resources for Abderhalden-Kaufmann-Lignac syndrome

Articles

Most recent articles on Abderhalden-Kaufmann-Lignac syndrome

Most cited articles on Abderhalden-Kaufmann-Lignac syndrome

Review articles on Abderhalden-Kaufmann-Lignac syndrome

Articles on Abderhalden-Kaufmann-Lignac syndrome in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Abderhalden-Kaufmann-Lignac syndrome

Images of Abderhalden-Kaufmann-Lignac syndrome

Photos of Abderhalden-Kaufmann-Lignac syndrome

Podcasts & MP3s on Abderhalden-Kaufmann-Lignac syndrome

Videos on Abderhalden-Kaufmann-Lignac syndrome

Evidence Based Medicine

Cochrane Collaboration on Abderhalden-Kaufmann-Lignac syndrome

Bandolier on Abderhalden-Kaufmann-Lignac syndrome

TRIP on Abderhalden-Kaufmann-Lignac syndrome

Clinical Trials

Ongoing Trials on Abderhalden-Kaufmann-Lignac syndrome at Clinical Trials.gov

Trial results on Abderhalden-Kaufmann-Lignac syndrome

Clinical Trials on Abderhalden-Kaufmann-Lignac syndrome at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Abderhalden-Kaufmann-Lignac syndrome

NICE Guidance on Abderhalden-Kaufmann-Lignac syndrome

NHS PRODIGY Guidance

FDA on Abderhalden-Kaufmann-Lignac syndrome

CDC on Abderhalden-Kaufmann-Lignac syndrome

Books

Books on Abderhalden-Kaufmann-Lignac syndrome

News

Abderhalden-Kaufmann-Lignac syndrome in the news

Be alerted to news on Abderhalden-Kaufmann-Lignac syndrome

News trends on Abderhalden-Kaufmann-Lignac syndrome

Commentary

Blogs on Abderhalden-Kaufmann-Lignac syndrome

Definitions

Definitions of Abderhalden-Kaufmann-Lignac syndrome

Patient Resources / Community

Patient resources on Abderhalden-Kaufmann-Lignac syndrome

Discussion groups on Abderhalden-Kaufmann-Lignac syndrome

Patient Handouts on Abderhalden-Kaufmann-Lignac syndrome

Directions to Hospitals Treating Abderhalden-Kaufmann-Lignac syndrome

Risk calculators and risk factors for Abderhalden-Kaufmann-Lignac syndrome

Healthcare Provider Resources

Symptoms of Abderhalden-Kaufmann-Lignac syndrome

Causes & Risk Factors for Abderhalden-Kaufmann-Lignac syndrome

Diagnostic studies for Abderhalden-Kaufmann-Lignac syndrome

Treatment of Abderhalden-Kaufmann-Lignac syndrome

Continuing Medical Education (CME)

CME Programs on Abderhalden-Kaufmann-Lignac syndrome

International

Abderhalden-Kaufmann-Lignac syndrome en Espanol

Abderhalden-Kaufmann-Lignac syndrome en Francais

Business

Abderhalden-Kaufmann-Lignac syndrome in the Marketplace

Patents on Abderhalden-Kaufmann-Lignac syndrome

Experimental / Informatics

List of terms related to Abderhalden-Kaufmann-Lignac syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Abdulkerim Yassin, M.B.B.S[2]

Synonyms and keywords: Abderhalden-Lignac-Kaufmann disease; nephropathic cystinosis

Overview

Abderhalden-Kaufmann-Lignac syndrome, also called Abderhalden-Lignac-Kaufmann disease or nephropathic cystinosis, is an autosomal recessive renal disorder of childhood comprising cystinosis and renal rickets. It is caused by mutation in the CTNS gene encoding for cystinosin, transporting cystine out of the lysosomes. A defect in the cystinosin leads to accumulation of excessive cystine crystals in the lsysosomes of all body cells and organs. The most commonly affected organs are the eyes and kidneys but it can also affect the thyroid, pancreas, gonads, muscles and CNS. The symptoms are renal calculi, osteomalacia, aminoaciduria, glycosuria, polyuria, chronic acidosis, hypophosphatemia with vitamin D-resistant rickets, and often with hypokalemia, photophobia, blepharospasm, hypothyroidism, primary hypogonadism in males, hypotonia, speech delay, motor impairment, cognitive dysfunction, Diabetes, hypopigmentation, coarsened facial features and impaired sweating. The diagnosis is made with measuring cystine levels in polymorphonuclear leukocytes or cultured fibroblasts. Molecular analysis of the cystinosin gene can be done for definitive diagnosis.The mainstay of treatment is cystine-depleting therapy with cysteamine. There are no established measures for the primary or secondary prevention of Abderhalden-Kaufmann-Lignac syndrome.

Historical Perspective

Abderhalden-Kaufmann-Lignac syndrome was first described by Emil Abderhalden, Swiss biochemist in 1903 as the familial cystine accumulation disease. Abderhalden referred to a child initially encountered by Eduard Kaufmann, a German physician. George Lignac, a Dutch pathologist, was the first to give more detailed systematic description of the disease and to associate cystinosis with its major clinical manifestations such as rickets, renal disease and growth retardation. The disease is named for Emil Abderhalden, Eduard Kaufmann and George Lignac.[1]

Classification

Abderhalden-Kaufmann-Lignac syndrome may be classified according to age of onset into three types[2]:

Pathophysiology

It is thought that Abderhalden-Kaufmann-Lignac syndrome is the result of CTNS gene mutation which encodes for cystinosin, a transporter protein which carries cystine from lysosomes to cytosol. A defect in the CTNS gene leads to a high level of cystine accumulation in the lysosome. It is transmitted in autosomal recessive pattern, where inheritance of one defective gene from each parents who are carrrier, put at risk of their 25% of children manifest the disease. The exact pathophysiology of the disease is still not properly understood but there are suggested mechanismsm.[3][4]

  1. Increased cystine levels in the lysosome links to enhanced apoptosis.
  2. lysosomal cystine accumulation leads to cellular ATP depletion.

Causes

The cause of Abderhalden-Kaufmann-Lignac syndrome is CTNS gene mutation in the lysosomal membrane trafficking protein called cystinosin, which causes to cystine accumulation in the lysosome of all body cells and organs, leads to apoptosis and cellular ATP depletion.It is a rare autosomal recessive lysosomal storage diseases.[5]

Differentiating Abderhalden-Kaufmann-Lignac syndrome from other Diseases

Abderhalden-Kaufmann-Lignac syndrome must be differentiated from other diseases that cause renal Fanconi syndrome, photophobia, blepharospasm , and rickets or osteomalacia, such as Lowe syndrome, Dent disease; Idiopathic fanconi syndrome.[1]

Epidemiology and Demographics

  • There is no racial predilection to Abderhalden-Kaufmann-Lignac syndrome.
  • Male are more commonly affected by Abderhalden-Kaufmann-Lignac syndrome than female. The male to female ratio is approximately 1.5 to 1.

Risk Factors

There are no established risk factors for Abderhalden-Kaufmann-Lignac syndrome.

Screening

There is insufficient evidence to recommend routine screening for Abderhalden-Kaufmann-Lignac syndrome.

Natural History, Complications, and Prognosis

If left untreated, Abderhalden-Kaufmann-Lignac syndrome may progress to develop chronic renal failure and extrarenal complications such as dwarfism, rickets, hyphothyroidism, hypogonadism, hypopigmentation, diabetes, distal vacuolar myopathy, osteoporosis, blindness, CNS complications such as Hypotonia, speech delay, neurocognitive dysfunction, and encephalopathy.[7][8]

Prognosis of Abderhalden-Kaufmann-Lignac syndrome depends on early diagnosis, and prompt starting and good compliance with cysteamine treatment. life expectancy can extend past 50 years.[5]

Diagnosis

The diagnosis of Abderhalden-Kaufmann-Lignac syndrome is made with clinical and laboratory findings. The diagnosis is confirmed by molecular analysis of the cystinosin gene.[1]

History and Symptoms

The hallmark of Abderhalden-Kaufmann-Lignac syndrome is early corneal cystine crystal deposition. The most common symptoms of Abderhalden-Kaufmann-Lignac syndrome include renal fanconi syndrome, dwarfism, and rickets. Other presenting symptoms of Abderhalden-Kaufmann-Lignac syndrome include photophobia, blepharospasm, aminoaciduria, glycosuria, hypokalemia, vomiting, feeding difficulties, decreased appetite, nephrolithiasis, nephrocalcinosis, distal muscle wasting and weakness, hypothyroidism, hypogonadism, hypopigmentation, diabetes.[9][10]

Physical Examination

The presence of cystine crystal in the cornea, growth failure, short stature, and knock-knees (valgus deformity) on physical examination is highly suggestive of Abderhalden-Kaufmann-Lignac syndrome.[1]

Laboratory Findings

An elevated Cystine concentrations 5-10 nmol half-cystine/mg cell protein in individuals who are homozygous for Abderhalden-Kaufmann-Lignac syndrome is other diagnostic finding.Reference range levels are below 0.2 nmol half-cystine/mg cell protein. When a fetus is at risk for Abderhalden-Kaufmann-Lignac syndrome, the cystine level can be measured in chorionic villi or cultured amniotic fluid cells. Laboratory findings consistent with the diagnosis of Abderhalden-Kaufmann-Lignac syndrome include serum electrolyte abnormalities such as hypokalemia, hypophosphatemia, hypocalcemia, low bicarbonate levels, hyponatremia, ABG to detect metabolic acidosis, and urine test for glycosuria, aminoaciduria, proteinuria.[1]

Electrocardiogram

There are no ECG findings associated with Abderhalden-Kaufmann-Lignac syndrome.

X-ray

There are no specific x-ray findings associated with Abderhalden-Kaufmann-Lignac syndrome. However, an x-ray may be helpful in the diagnosis of complications of Abderhalden-Kaufmann-Lignac syndrome, which includes osteoporosis, urinary tract calcifications and rickets[9].

Echocardiography or Ultrasound

There are no specific echocardiography findings associated with Abderhalden-Kaufmann-Lignac syndrome. However, an echocardiography may be helpful in the diagnosis of Left ventricular hypertrabeculation/non-compaction (LVHT) associated with accumulation of cystine in the cardiac muscles.[11] There are no specific ultrasound findings associated with Abderhalden-Kaufmann-Lignac syndrome. However, an ultrasound may be helpful in the diagnosis of complications of Abderhalden-Kaufmann-Lignac syndrome, which include nephrolithiasis, and renal medullary nephrocalcinosis.[9]

CT scan

There are no specific CT scan findings associated with Abderhalden-Kaufmann-Lignac syndrome. However, a CT scan may be helpful in the diagnosis of complications of Abderhalden-Kaufmann-Lignac syndrome, which include isolated ventricular non-compaction Central nervous system abnormalities, nephrolithiasis, papilledema and renal medullary nephrocalcinosis.[12][13]

MRI

There are no specific MRI findings associated with Abderhalden-Kaufmann-Lignac syndrome. However, a MRI may be helpful in the diagnosis of complications of Abderhalden-Kaufmann-Lignac syndrome, which include Central nervous system abnormalities, rickets, papilledema, and osteoporosis. cognitive dysfunction could be related to abnormalities in the cerebral white matter microstructure and has been demonstrated using in magnetic resonance diffusion tensor imaging.[13]

Other Imaging Findings

other imaging findings associated with Abderhalden-Kaufmann-Lignac syndrome is decreased bone mass evaluated by Bone density scan[9].

Other Diagnostic Studies

Other diagnostic studies for Abderhalden-Kaufmann-Lignac syndrome include slit-lamp examination, which demonstrates cystine crystals deposition in the cornea[2].

Treatment

Medical Therapy

Symptomatic treatments:

The mainstay of treatment for Abderhalden-Kaufmann-Lignac syndrome is cysteamine. It is available in two formulations; tablet and eyedrops. cysteamine, facilitates lysosomal cystine clearance and delays progression to ESRD, significantly improves growth, decreases the frequency and severity of extrarenal complications, and is associated with extended life expectancy; however, no curative treatment is yet available.[1]

Surgery

The mainstay of treatment for Abderhalden-Kaufmann-Lignac syndrome is medical therapy. Surgery is may be needed for patients with complications of Abderhalden-Kaufmann-Lignac syndrome such as End Stage Renal Disease or nephrolithiasis.[14][10]

Primary Prevention

There are no established measures for the primary prevention of Abderhalden-Kaufmann-Lignac syndrome[1].

Secondary Prevention

There are no established measures for the secondary prevention of Abderhalden-Kaufmann-Lignac syndrome[1].

Related Chapters

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 Gahl WA, Thoene JG, Schneider JA (2002). "Cystinosis". N Engl J Med. 347 (2): 111–21. doi:10.1056/NEJMra020552. PMID 12110740.
  2. ↑ 2.0 2.1 Emma F, Nesterova G, Langman C, Labbé A, Cherqui S, Goodyer P; et al. (2014). "Nephropathic cystinosis: an international consensus document". Nephrol Dial Transplant. 29 Suppl 4: iv87–94. doi:10.1093/ndt/gfu090. PMC 4158338. PMID 25165189.
  3. ↑ Park M, Helip-Wooley A, Thoene J (2002). "Lysosomal cystine [[storage]] augments [[apoptosis]] in [[cultured]] human [[fibroblasts]] and [[renal]] [[tubular]] [[epithelial]] cells". J Am Soc Nephrol. 13 (12): 2878–87. doi:10.1097/01.asn.0000036867.49866.59. PMID 12444206. URL–wikilink conflict (help)
  4. ↑ Sansanwal P, Yen B, Gahl WA, Ma Y, Ying L, Wong LJ; et al. (2010). "Mitochondrial autophagy promotes cellular injury in nephropathic cystinosis". J Am Soc Nephrol. 21 (2): 272–83. doi:10.1681/ASN.2009040383. PMC 2834547. PMID 19959713.
  5. ↑ 5.0 5.1 Elmonem MA, Veys KR, Soliman NA, van Dyck M, van den Heuvel LP, Levtchenko E (2016). "Cystinosis: a review". Orphanet J Rare Dis. 11: 47. doi:10.1186/s13023-016-0426-y. PMC 4841061. PMID 27102039.
  6. ↑ Greco M, Brugnara M, Zaffanello M, Taranta A, Pastore A, Emma F (2010). "Long-term outcome of nephropathic cystinosis: a 20-year single-center experience". Pediatr Nephrol. 25 (12): 2459–67. doi:10.1007/s00467-010-1641-8. PMID 20803298.
  7. ↑ Fivush B, Green OC, Porter CC, Balfe JW, O'Regan S, Gahl WA (1987). "Pancreatic endocrine insufficiency in posttransplant cystinosis". Am J Dis Child. 141 (10): 1087–9. doi:10.1001/archpedi.1987.04460100065027. PMID 3307383.
  8. ↑ Fink JK, Brouwers P, Barton N, Malekzadeh MH, Sato S, Hill S; et al. (1989). "Neurologic complications in long-standing nephropathic cystinosis". Arch Neurol. 46 (5): 543–8. doi:10.1001/archneur.1989.00520410077027. PMID 2712751.
  9. ↑ 9.0 9.1 9.2 9.3 Florenzano P, Ferreira C, Nesterova G, Roberts MS, Tella SH, de Castro LF; et al. (2018). "Skeletal Consequences of Nephropathic Cystinosis". J Bone Miner Res. 33 (10): 1870–1880. doi:10.1002/jbmr.3522. PMID 29905968.
  10. ↑ 10.0 10.1 Ariceta G, Giordano V, Santos F (2019). "Effects of [[long-term]] [[cysteamine]] [[treatment]] in patients with [[cystinosis]]". Pediatr Nephrol. 34 (4): 571–578. doi:10.1007/s00467-017-3856-4. PMC 6394685. PMID 29260317. URL–wikilink conflict (help)
  11. ↑ Jenni R, Oechslin E, Schneider J, Attenhofer Jost C, Kaufmann PA (2001). "Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy". Heart. 86 (6): 666–71. doi:10.1136/heart.86.6.666. PMC 1730012. PMID 11711464.
  12. ↑ Stöllberger C, Finsterer J (2006). "Pitfalls in the diagnosis of left ventricular [[hypertrabeculation/non-compaction]]". Postgrad Med J. 82 (972): 679–83. doi:10.1136/pgmj.2006.046169. PMC 2653912. PMID 17068279. URL–wikilink conflict (help)
  13. ↑ 13.0 13.1 Bava S, Theilmann RJ, Sach M, May SJ, Frank LR, Hesselink JR; et al. (2010). "Developmental changes in cerebral white matter [[microstructure]] in a disorder of lysosomal storage". Cortex. 46 (2): 206–16. doi:10.1016/j.cortex.2009.03.008. PMC 3351112. PMID 19427638. URL–wikilink conflict (help)
  14. ↑ Nesterova G, Gahl WA (2013). "Cystinosis: the evolution of a treatable disease". Pediatr Nephrol. 28 (1): 51–9. doi:10.1007/s00467-012-2242-5. PMC 3505515. PMID 22903658.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Abderhalden-Kaufmann-Lignac_syndrome&oldid=1716488"