Складнощі діагностики рідкісної вродженої мітохондріальної патології — комбінованого дефіциту окисного фосфорилювання 26-го типу в дитини раннього віку: клінічний випадок

Abstract

Hereditary mitochondrial diseases are a consequence of congenital errors in energy metabolism with very variable and predominantly multisystem manifestations, they require differential diagnosis with a wide range of phenotypically similar nosologies, and their verification is a complex problem with a need of a multidisciplinary approach. The article describes a rare clinical case diagnosed in a girl of early age of a congenital mitochondrial pathology with autosomal recessive inheritance — a combined oxidative phosphorylation deficiency of type 26 (COXPD-26) due to two mutations in the heterozygous state of the TRMT5 gene (tRNA methyltransferase 5) on the chromosome 14q23. The patient's illness was accompanied by a debut from birth and was characterized by insufficient weight gain, manifestations of cardiomyopathy, repeated intercurrent infectious diseases with increased activity of blood transaminases, creatine kinase-MB, hepatopathy with hypoalbuminemia, convulsive syndrome, intolerance to valproic acid, progressive delay in stato-kinetic and psychoverbal development, that is, the symptomatology was characterized by progression, multisystem character with predominant damage to the heart, liver and nervous system. The diagnostic algorithm for mitochondrial diseases is one of the most complex in medical practice. In young children, persistent or progressive multisystem disorder of unknown etiology, unknown multiple complex neurological manifestations or neurological monosymptom with involvement of other systems, less often — specific clinical symptoms; persistent lactic acidosis, other positive or questionable laboratory screening findings are suspicious of probable mitochondrial pathology. Numerous hospitalizations, repeated consultations by different specialists, multiple additional labtests, and multiple conflicting diagnoses may indicate a possible mitochondrial pathology. Only whole exome sequencing of a blood sample with an analysis of variations in the number of copies of genes and genomic sequencing of a new generation with targeted genetic testing made it possible to diagnose in a child a hereditary metabolic disorder from the group of defects in the mitochondrial respiratory chain — a combined deficiency of oxidative phosphorylation type 26, previously described in only a few patients. The research was carried out in accordance with the principles of the Helsinki declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: mitochondrial pathology, combined deficiency of oxidative phosphorylation of type 26 (COXPD-26), clinical case.