Expanding the Clinical Spectrum of Mitochondrial Phosphate Carrier Deficiency: A Case Report With Literature Review.

Abstract

Mitochondrial phosphate carrier (PiC) deficiency, caused by pathogenic variants in the SLC25A3 gene, is a rare autosomal recessive disorder primarily presenting with early-onset hypertrophic cardiomyopathy (HCMP), muscular hypotonia, and respiratory failure. This report presents a case of a 32-year-old female manifesting with HCMP and myopathy beyond the neonatal period. The patient's neuromotor development was initially normal, but from 1.5 years of age, she exhibited fatigue and muscle weakness, particularly after walking. Muscle biopsy revealed normal muscle fiber size with a predominance of type 1 fibers. The histopathology showed a mild increase in cytochrome c oxidase (COX) and succinate dehydrogenase (SDH) activity, suggesting mitochondrial myopathy. The patient was treated with mitochondrial therapy, along with a fat-rich diet. Despite clinical improvement, lactate levels remained elevated. Genetic analysis identified a homozygous splicing variant in the SLC25A3 gene [NM_005888.4:c.158-9A>G (IVS2-9A>G)], consistent with mitochondrial PiC deficiency. At the age of 32 years, the patient remained stable with HCMP and persistently high lactate levels. This case supports the expansion of the clinical spectrum of mitochondrial PiC deficiency by presenting a patient with a later-onset phenotype compared to previously reported cases.