Background: Mitochondrial DNA-depletion syndromes (MDDS) usually present with a wide spectrum of clinical manifestations, such as weakness, hypotonia, developmental delay, and/or seizures, and are categorized as myopathic, encephalomyopathic, hepatocerebral, or multisystemic. The condition is typically fatal in infancy and early childhood although some with the myopathic variant have survived to their teenage years and some with the SUCLA2 encephalomyopathic variant have survived into adulthood. There is currently no curative treatment for any form of MDDS.
Case Presentation: A female patient born at 37 weeks presented with intrauterine growth restriction, the infant was found to have jaundice, cataract, and metabolic diseases were suspected. Patient's liver enzymes continued to measure twice as high for the patient's age and the patient presented with mild cholestasis. At the age of 2 months, the patient was brought back by the parents because of fever, persistent crying, poor oral intake, and bloody stool. The following observations were noted: progressive liver failure, severe coagulopathy, ascites associated with the development of spontaneous bacterial peritonitis. Then, a homozygous variant c.763-766dup p.(Phe256*) in DGUOK was discovered.
Conclusion: We report a novel homozygous variant c.763_766dup p.(Phe256*) mutation discovered in the DGUOK gene (OMIM: 601465), causing fatal progressive liver failure in a three-month-old Saudi infant of asymptomatic consanguineous parents. This genotype is associated with a severe clinical presentation, and the infant died at the age of 3 months.
Case report, mitochondrial diseases, hepatocerebral, syndrome, mitochondrial DNA depletion syndromes