Acknowledgement of ARC Syndrome (Arthrogryposis-Renal Dysfunction-Cholestasis) has not been added yet.

ARC Syndrome is an extremely rare condition, with fewer than 100 cases reported in the medical literature. Its exact prevalence is unknown, but it is considered to be very low. The syndrome appears to affect both males and females equally and has been reported in various ethnic groups.

 

Name	Abbreviation
Arthrogryposis-Renal Tubular Dysfunction-Cholestasis Syndrome
Infantile Arthrogryposis-Renal Dysfunction-Cholestasis Syndrome

ARC Syndrome can be caused by mutations in either the VPS33B or VIPAR (also known as VIPAS39) genes, which encode proteins essential for vesicular trafficking and cellular transport processes. These proteins are involved in the regulation of various cellular functions, including the movement of proteins and lipids within cells. Mutations in these genes disrupt normal cellular processes, leading to the characteristic symptoms of ARC Syndrome. The mutations associated with ARC syndrome are passed from parent to offspring through the autosomal recessive pattern of inheritance. To read more about genetic inheritance patterns, refer to our  RareShare Guide on Genetic Inheritance.

 

The symptoms of ARC Syndrome are diverse and involve multiple organ systems:

• Arthrogryposis: This refers to congenital joint contractures that are present at birth. Affected infants have stiff, immobile joints, particularly in the limbs, which can limit movement and function.

• Renal Dysfunction: Renal involvement can present as renal tubular acidosis, which leads to metabolic acidosis and electrolyte imbalances. Nephrotic syndrome, characterized by proteinuria, hypoalbuminemia, and edema, may also be present.

• Cholestasis: Liver dysfunction manifests as cholestasis, which is the impaired flow of bile from the liver. This can lead to jaundice, pruritus (itching), and an increased risk of liver cirrhosis and failure.

• Additional Symptoms: Other features may include failure to thrive, developmental delay, recurrent infections, ichthyosis (scaly skin), and dysmorphic facial features such as a broad nasal bridge and low-set ears.

Diagnosis of ARC Syndrome is based on clinical evaluation, the presence of characteristic symptoms, and genetic testing. The diagnosis is often suspected in neonates with the triad of arthrogryposis, renal dysfunction, and cholestasis. A thorough physical examination and detailed medical history are crucial for identifying the syndrome.

 

Several diagnostic tests are used to confirm ARC Syndrome:

• Genetic Testing: Sequencing of the VPS33B and VIPAR genes to identify mutations confirms the diagnosis.

• Liver Function Tests: Blood tests to measure liver enzymes and bile acids help assess the extent of liver dysfunction.

• Renal Function Tests: Blood and urine tests to evaluate kidney function, including serum electrolytes and urine protein levels.

• Imaging Studies: Ultrasound or MRI of the abdomen and kidneys to visualize structural abnormalities.

There is no cure for ARC Syndrome, and treatment is primarily aimed at relieving symptoms:

• Management of Arthrogryposis: Physical therapy and orthopedic interventions may help improve joint mobility and function.

• Renal Dysfunction: Management includes electrolyte supplementation, bicarbonate therapy for acidosis, and treatment of nephrotic syndrome with diuretics and albumin replacement.

• Cholestasis: Treatment involves ursodeoxycholic acid to improve bile flow, nutritional support with fat-soluble vitamins, and management of pruritus.

• Multidisciplinary Approach: Due to the complexity of the syndrome, a multidisciplinary team including pediatricians, nephrologists, hepatologists, and geneticists is essential for comprehensive care.

Prognosis 

The prognosis for individuals with ARC Syndrome is generally poor. Most affected infants have a significantly shortened life expectancy, often succumbing to complications of liver or kidney failure, severe infections, or failure to thrive within the first few years of life. However, the prognosis can vary, and with appropriate medical care, some individuals may survive longer and achieve a better quality of life. Continued research and advances in treatment may further improve outcomes for affected individuals in the future.

 

Tips or Suggestions of ARC Syndrome (Arthrogryposis-Renal Dysfunction-Cholestasis) has not been added yet.

1. https://rarediseases.org/rare-diseases/arthrogryposis-renal-dysfunction-cholestasis-syndrome/ 

2. Gissen, P., Tee, L., Johnson, C. A., et al. (2006). "Clinical and molecular genetic features of ARC syndrome." Human Genetics, 120(3), 396-409.

3. Sivagnanam, M., Mueller, J. L., Lee, H., et al. (2008). "Identification of disease-causing mutations in a child with very early onset inflammatory bowel disease and intractable diarrhea by whole-exome sequencing." Gastroenterology, 134(2), 382-389.

4. Cullinane, A. R., Straatman-Iwanowska, A., Zaucker, A., et al. (2010). "Molecular investigations of VPS33B mutations expand the phenotypic spectrum of ARC syndrome." Human Mutation, 31(10), 1176-1182.

5. Huybrechts, S., Sproat-Emison, E., Lees, M., et al. (2009). "The genetic basis of ARC syndrome: Ten years on." International Journal of Biochemistry & Cell Biology, 41(4), 828-835.

6. Lo, B., Li, L., Gissen, P., et al. (2005). "Requirement of VPS33B, a member of the Sec1/Munc18 protein family, in megakaryocyte and platelet alpha-granule biogenesis." Blood, 106(13), 4159-4166.