Navajo neurohepatopathy

Navajo neurohepatopathy (NNH), also known as Navajo familial neurological disease or Navajo neuropathy, is a rare autosomal recessive disorder caused by mutations in the MPV17 gene, which encodes a mitochondrial inner membrane protein involved in mitochondrial DNA (mtDNA) maintenance. The disease results in mitochondrial DNA depletion, primarily affecting the liver and nervous system. It occurs almost exclusively in individuals of Navajo (Diné) ancestry and is considered part of the spectrum of MPV17-related mitochondrial DNA maintenance defect. NNH presents with a range of clinical features that can vary in severity. The condition primarily affects the liver, peripheral nervous system, and corneas. Key manifestations include progressive liver disease that can range from hepatomegaly to liver failure and cirrhosis, sensory and motor peripheral neuropathy leading to weakness and loss of sensation in the extremities, and corneal anesthesia and ulceration that can result in scarring and vision impairment. Additional features may include failure to thrive, short stature, sexual infantilism, and recurrent infections. Three clinical presentations have been described: infantile onset with severe liver disease and early death, childhood onset with progressive neuropathy and liver involvement, and a classic form presenting in later childhood with prominent neuropathy and corneal disease. There is currently no cure for Navajo neurohepatopathy. Treatment is supportive and symptomatic, focusing on management of liver disease, prevention of corneal complications through protective measures, physical therapy for neuropathy, and nutritional support. Liver transplantation has been considered in cases of severe hepatic involvement, though outcomes may be complicated by the multisystem nature of the disease. Genetic counseling is recommended for affected families.

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