Arthrogryposis–renal dysfunction–cholestasis syndrome

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  Diagram showing autosomal recessive inheritance pattern

Arthrogryposis–Renal Dysfunction–Cholestasis Syndrome

Arthrogryposis–Renal Dysfunction–Cholestasis Syndrome (ARC syndrome) is a rare genetic disorder characterized by the combination of arthrogryposis, renal dysfunction, and cholestasis. It is an autosomal recessive condition, meaning that it occurs when an individual inherits two copies of a mutated gene, one from each parent.

Clinical Features

ARC syndrome presents with a triad of symptoms:

• Arthrogryposis: This refers to congenital joint contractures, which are present at birth. Affected individuals have limited movement in multiple joints due to abnormal muscle development and fibrosis.

• Renal Dysfunction: This can manifest as renal tubular acidosis, nephrogenic diabetes insipidus, or other forms of kidney impairment. The kidneys may not function properly, leading to electrolyte imbalances and other complications.

• Cholestasis: This is a condition where bile flow from the liver is reduced or blocked, leading to jaundice, pruritus, and malabsorption of fat-soluble vitamins. It can result in liver damage over time.

Additional features may include failure to thrive, developmental delay, and ichthyosis.

Genetics

ARC syndrome is caused by mutations in the VPS33B or VIPAR (also known as VIPAS39) genes. These genes are involved in the trafficking of proteins within cells, particularly in the endosomal and lysosomal pathways. Mutations disrupt normal cellular processes, leading to the symptoms observed in ARC syndrome.

Diagnosis

Diagnosis of ARC syndrome is based on clinical evaluation, family history, and genetic testing. The presence of the characteristic triad of symptoms, along with genetic confirmation of mutations in the VPS33B or VIPAR genes, supports the diagnosis.

Management

There is no cure for ARC syndrome, and management is primarily supportive. Treatment focuses on addressing the individual symptoms:

• For arthrogryposis, physical therapy and orthopedic interventions may help improve joint mobility.
• Renal dysfunction may require electrolyte management and, in some cases, dialysis.
• Cholestasis is managed with medications to improve bile flow and nutritional support to address malabsorption.

Prognosis

The prognosis for individuals with ARC syndrome is generally poor, with many affected children not surviving beyond the first few years of life due to complications from liver and kidney failure.

Related Pages

• Arthrogryposis
• Cholestasis
• Renal dysfunction
• Genetic disorders