부산대학교 도서관

Defects in the mitochondrial DNA (mtDNA) cause mtDNA depletion syndrome (MTDPS), a subclass of mitochondrial disorders that are genetically and phenotypically heterogeneous. MTDPS is a rare autosomal recessive disease caused by a mutation of a nuclear gene named FBXL4 (F-box and leucine-rich repeat protein 4), located on chromosome 6. This nuclear-encoded mitochondrial protein plays a vital role in mitochondrial bioenergetics, mtDNA maintenance, and mitochondrial dynamics. Pathogenic variants in the FBXL4 gene reduce mtDNA synthesis, resulting in a large decrease in the mtDNA content in cells, which is essential for normal energy production. These pathogenic variants in the FBXL4 gene are associated with an encephalomyopathy MTDPS type 13 (MTDPS13), a rare and severe mul­tisystemic disorder mainly characterized by infant-onset encephalomyopathy and lactic acidosis, developmental delay, hypotonia with feeding difficulties and failure to thrive. Other features may include the central nervous system and the ophthalmologic, cardiac, gastrointestinal, genito­urinary, and immunological systems. Herein, we report the case of an infant born to consanguineous Pakistani parents with an early onset of severe lactic acidosis, hypotonia, feeding difficulties, hypertro­phic cardiomyopathy, supraventricular tachycardia, and transient neutro­penia harboring a homozygous variant in the FBXL4 (c.370C>T [p.Q124*]) gene. This variant was identified in the patient’s parents in heterozygosity. He started medical treatment (with coenzyme Q10, propranolol, and sodium bicarbonate) and multidisciplinary support. As a result, a progressive improvement in postural tone and feeding autonomy was observed during the first months of life. Therefore, encephalomyopathy MTDPS13 should be suspected when dealing with patients with severe congenital lactic acidosis and developmental impairment.