Clinical observation of a newborn with mitochondrial hepatopathy due to a mutation in the MPV17 gene

Mitochondrial deoxyribonucleic acid depletion syndrome is a group of diseases with autosomal recessive inheritance associated with mutations in nuclear genes that encode components of the respiratory chain of "cellular energy stations". The disease is characterized by a decrease in the number of copies of the genetic material of mitochondria and, as a consequence, irreversible loss of their oxidative capacity with the accumulation of damaging metabolites. Currently, the pathology tends to spread and occurs with a frequency of 4.7 to 12.5 per 100,000 population, especially in some regions (in our case, a patient from the North Caucasus region is described). Heterogeneity of clinical manifestations is due to the variability of gene defects: myopathic, encephalomyopathic, and hepatocerebral forms of the disease are distinguished. Diseases associated with depletion of mitochondrial deoxyribonulinic acid manifest in the early neonatal period with critical metabolic disorders (hypoglycemia, lactatacidosis), clinically manifested by neurological deficit, liver failure and often lead to death. The development of liver cirrhosis in such patients requires liver transplantation, the efficacy of which is less than 50%. This article describes a clinical case of severe depletion syndrome associated with a homozygous mutation in the acceptor splice site, intron 7 of the MPV17 gene (OMIM #251880), (chr2:27532851T>C) resulting in a nucleotide substitution (NM_002437.5: c.462-2A>G), not previously described in the Russian-language literature. In contrast to most of the described observations, the first clinical manifestations in the presented patient were erased and included signs of lethargic baby syndrome. Despite symptomatic therapy, the patient required liver transplantation at the age of 4 months due to the development of cirrhosis. The article highlights the issues of clinic, diagnosis, and treatment of mitochondrial deoxyribonucleic acid depletion syndrome on the example of the observed child and patients previously described both in Russian and foreign literature. Key words: mitochondrial DNA depletion syndrome, hepatocerebral form, neonatal cholestasis, liver, liver failure, neurologic disorders, liver transplantation