Abderhalden-Kaufmann-Lignac syndrome

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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

File:Autorecessive.svg

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 in 1903. The disease is named for Emil Abderhalden, Eduard Kaufmann and George Lignac.

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.

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.

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 syndrome is 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

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.

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 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.

Echocardiography or Ultrasound

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

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 nephrolithiasis, papilledema and renal medullary nephrocalcinosis.

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 rickets, papilledema, and osteoporosis.

Other Imaging Findings

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

Other Diagnostic Studies

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

Treatment

Medical Therapy

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.

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.

Primary Prevention

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

Secondary Prevention

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

Related Chapters

• Cystinosin