Mitochondrial Phosphate Carrier Deficiency

A number sign (#) is used with this entry because mitochondrial phosphate carrier deficiency can be caused by mutation in the SLC25A3 gene (600370).

Clinical Features

Mayr et al. (2007) described 2 sisters, offspring of nonconsanguineous Turkish parents, with mitochondrial phosphate carrier deficiency. The younger sister presented at age 12 hours with cyanosis and muscular hypotonia that necessitated intensive care treatment. Echocardiography revealed hypertrophic cardiomyopathy with low cardiac output. Lactate was constantly elevated in plasma. Cardiac hypertrophy was progressive. Severe muscular hypotonia and failure to thrive persisted. At age 4 months, she died from heart failure. Histologic examination of a muscle biopsy showed lipid myopathy with lipid accumulation in both fiber types, prominent in type I fibers. The elder sister presented at age 10 hours with muscular hypotonia, respiratory distress, metabolic acidosis (pH 6.9), and lactic acidosis that necessitated intensive care treatment. Artificial ventilation was necessary for 3 months. She developed increasing hypertrophic cardiomyopathy. Metabolic workup revealed constantly elevated plasma lactate and an increased lactate:pyruvate ratio of 62. At age 9 months, she died from intractable low-output hypertrophic heart failure.

Molecular Genetics

In 2 sibs with mitochondrial phosphate carrier deficiency, Mayr et al. (2007) identified homozygosity for a mutation in the alternatively spliced exon 3A of the SLC25A3 gene (600370.0001), which produces the heart/muscle-specific isoform of mitochondrial phosphate carrier protein. In both patients, functional investigation of intact mitochondria showed a deficiency of ATP synthetase in muscle but not in fibroblasts, which correlated with the tissue-specific expression of exon 3A in muscle versus exon 3B in fibroblasts.