MPV17-related hepatocerebral mitochondrial DNA depletion syndrome is an autosomal recessive disease that is prevalent among Navajo children in the southwestern United States. It is characterized by infantile-onset liver dysfunction that typically progresses to liver failure, neurologic involvement, including developmental delay, frequently observed hypotonia, and muscle weakness, ataxia, seizures, and motor and sensory peripheral neuropathy in some patients, failure to thrive; and metabolic derangements, including lactic acidosis and hypoglycemic crises. Approximately 30 cases have been reported in the scientific literature.
The diagnosis is based on mtDNA content that is severely reduced in liver tissue (<20% of controls) and in muscle tissue (<30% of controls). Molecular genetic testing of MPV17 gene can be used to detect mutations in the affected children. The disease is fatal, with liver failure often leading to death in infancy or early childhood.
AlSaman et al. (2012) reported a Saudi boy born to first cousin parents with hepatocerebral form of mitochondrial DNA depletion syndrome, who was admitted on the second day of birth because of poor feeding, vomiting, and episodes of hypoglycemia. At the age of 12 months he presented with failure to thrive and dehydration. He also had developmental delay. He was hypotonic, but was able to move his limbs freely. His skin was scaly, pruritic, showing eczematous changes and reticular pigmentation. Sequencing of the MPV17 gene revealed a homozygous mutation. The patient had episodes of hypoglycemia and continued vomiting; he died after 1 month of hospital admission due to complications of liver failure.
Sarkhy et al. (2014) described a Saudi infant with hepatocerebral mitochondrial DNA depletion syndrome. MPV17 sequencing revealed the presence of a novel homozygous variant; c.278A>C (p.Q93P).
Al-Hussaini studied 20 infants with suspected hepatocerebral mitochondrial DNA depletion syndrome in Saudi Arabia. Mutations in the MPV17 and DGUOK genes were identified in 11 of these patients. All 11 of these patients had cholestasis, which was followed by rapidly progressive liver failure and death in infancy.