arthrogryposis, renal dysfunction, and cholestasis 1

Arthrogryposis, renal dysfunction, and cholestasis 1 is a multisystem condition that primarily affects the liver, kidneys, and musculoskeletal system. It is caused by mutations in the VPS33B gene, which play a key role in cellular trafficking processes. Affected individuals typically present in infancy with persistent jaundice, renal abnormalities, and joint contractures. As precise prevalence data are not available, the rarity of the condition is emphasized and outcomes continue to evolve with modern care.

The clinical presentation of this condition is marked by a combination of liver, kidney, and musculoskeletal findings. Virtually all affected individuals exhibit jaundice, renal tubular acidosis, aminoaciduria, and conjugated hyperbilirubinemia, which are considered characteristic features. In addition, many patients demonstrate arthrogryposis multiplex congenita, while a subset may also experience being small for gestational age, nephrocalcinosis, giant cell hepatitis, and intrahepatic biliary atresia. Less commonly, features such as atrial septal defect, oligohydramnios, lissencephaly, nephrogenic diabetes insipidus, abnormal bleeding, renal tubular atrophy, hearing impairment, and thrombocytopenia have been reported. Not all individuals experience all features, and severity varies considerably.

This condition results from pathogenic variants in the VPS33B gene. The VPS33B protein is important for proper intracellular trafficking and cellular organization, and its disruption leads to the complex multisystem findings seen in affected individuals. Inheritance is autosomal recessive, meaning that an affected individual inherits two copies of the altered gene, one from each parent. Consequently, families with shared ancestry may have an increased likelihood of both parents carrying the mutation, and genetic counseling is recommended to help families understand the implications.

Currently, management focuses on supportive care and symptom management, with treatment plans tailored to each individual’s needs. Because there are no approved treatments specific to this condition, care typically involves a multidisciplinary team that provides regular surveillance to detect potential complications early. In practice, supportive interventions aim to manage hepatic, renal, and musculoskeletal issues, while ongoing monitoring and specialist consultation help guide adjustments in care as the condition evolves. Patients should discuss treatment options with their healthcare team, and genetic counseling is recommended for families.

Outcomes for individuals with arthrogryposis, renal dysfunction, and cholestasis 1 can vary significantly based on the severity of symptoms, age at diagnosis, and access to specialized care. With current standards of care, many individuals benefit from early intervention and ongoing, multidisciplinary management, which can help address the complex, multisystem nature of the condition. That the clinical course may include periods of stabilization as well as potential progression in some organ systems. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to connect with genetic counselors and specialist care teams for ongoing support and guidance.