Клиническое наблюдение пациента с синдромом истощения митохондриальной ДНК

The article reports clinical case of early neonatal manifestation of a rare genetic disease – mitochondrial DNA depletion syndrome, confirmed in laboratory in Russia. Mutations of FBXL4, which encodes an orphan mitochondrial F-box protein, involved in the maintenance of mitochondrial DNA (mtDNA), ultimately leading to disruption of mtDNA replication and decreased activity of mitochondrial respiratory chain complexes. It’s a reason of abnormalities in clinically affected tissues, most of all the muscular system and the brain. In our case hydronephrosis on the right, subependimal cysts of the brain, partial intestinal obstruction accompanied by polyhydramnios were diagnosed antenatal. Baby’s condition at birth was satisfactory and worsened dramatically towards the end of the first day of life. Clinical presentation includes sepsis-like symptom complex, neonatal depression, muscular hypotonia, persistent decompensated lactic acidosis, increase in the concentration of mitochondrial markers in blood plasma and urine, and changes in the basal ganglia of the brain. Imaging of the brain by magnetic resonance imaging (MRI) demonstrated global volume loss particularly the subcortical and periventricular white matter with significant abnormal signal in bilateral basal ganglia and brainstem with associated delayed myelination. Differential diagnosis was carried out with hereditary diseases that occur as a «sepsis-like» symptom complex, accompanied by lactic acidosis: a group of metabolic disorders of amino acids, organic acids, β-oxidation defects of fatty acids, respiratory mitochondrial chain disorders and glycogen storage disease. The diagnosis was confirmed after sequencing analysis of 62 mytochondrial genes by NGS (Next Generation Sequencing). Reported disease has an unfavorable prognosis, however, accurate diagnosis is very important for genetic counseling and helps prevent the re-birth of a sick child in the family.