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.
Historical Perspective
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
Abderhalden-Kaufmann-Lignac syndrome may be classified according to age of onset into three types:
- 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 mechanismsm.
- Increased cystine levels in the lysosome links to enhanced apoptosis.
- 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.
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 and Idiopathic fanconi syndrome.
Epidemiology and Demographics
- The incidence of Abderhalden-Kaufmann-Lignac syndrome is approximately 0.5-1 per 100,000 live births worldwide.
- 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.
- 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.
- 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.
- Abderhalden-Kaufmann-Lignac syndrome is a rare disease that tends to affect infants and adolescent.
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, distal vacuolar myopathy, osteoporosis, diabetes, and blindness.
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.
Diagnosis
The diagnosis of Abderhalden-Kaufmann-Lignac syndromeis made with clinical and laboratory findings. The diagnosis is confirmed by molecular analysis of the cystinosin gene.
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.
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].
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Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].
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The presence of [finding(s)] on physical examination is diagnostic of [disease name].
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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.
Electrocardiogram
There are no ECG findings associated with [disease name].
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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
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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
There are no echocardiography/ultrasound findings associated with [disease name].
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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].
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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
There are no CT scan findings associated with [disease name].
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[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].
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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
There are no MRI findings associated with [disease name].
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[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].
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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
There are no other imaging findings associated with [disease name].
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[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
There are no other diagnostic studies associated with [disease name].
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[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].
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Treatment
Medical Therapy
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
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Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
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The majority of cases of [disease name] are self-limited and require only supportive care.
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[Disease name] is a medical emergency and requires prompt treatment.
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The mainstay of treatment for [disease name] is [therapy].
OR The optimal therapy for [malignancy name] depends on the stage at diagnosis.
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[Therapy] is recommended among all patients who develop [disease name].
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Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
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Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
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Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
Surgery
Surgical intervention is not recommended for the management of [disease name].
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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]
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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].
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The feasibility of surgery depends on the stage of [malignancy] at diagnosis.
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Surgery is the mainstay of treatment for [disease or malignancy].
Primary Prevention
There are no established measures for the primary prevention of [disease name].
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There are no available vaccines against [disease name].
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Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
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[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
There are no established measures for the secondary prevention of [disease name].
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Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].