Pathologic Variants of the Mitochondrial Phosphate Carrier SLC25A3: Two New Patients and Expansion of the Cardiomyopathy/Skeletal Myopathy Phenotype With and Without Lactic Acidosis

• Published in: JIMD Reports, Volume 19 Vol. 19; pp. 59 - 66
• Main Authors: Bhoj, E. J., Li, M., Ahrens-Nicklas, R., Pyle, L. C., Wang, J., Zhang, V. W., Clarke, C., Wong, L. J., Sondheimer, N., Ficicioglu, C., Yudkoff, M.
• Format: Book Chapter Journal Article
• Language: English
• Published: Berlin, Heidelberg Springer Berlin Heidelberg 01-01-2015
• Series: JIMD Reports
• Subjects: Alpha Galactosidase; Hypertrophic Cardiomyopathy; Lactic Acidosis; Patent Ductus Arteriosus; Skeletal Myopathy
• ISBN: 9783662461891; 3662461897
• ISSN: 2192-8304; 2192-8312
• DOI: 10.1007/8904_2014_364

Variants in the SLC25A3 gene, which codes for the mitochondrial phosphate transporter (PiC), lead to a failure of inorganic phosphate (Pi) transport across the mitochondrial membrane, which is required in the final step of oxidative phosphorylation. The literature described two affected sibships with variants in SLC25A3; all cases had skeletal myopathy and cardiomyopathy (OMIM 610773). We report here two new patients who had neonatal cardiomyopathy; one of whom did not have skeletal myopathy nor elevated lactate. Patient 1 had a homozygous splice site variant, c.158-9A>G, which has been previously reported in a Turkish family. Patient 2 was found to be a compound heterozygote for two novel variants, c.599T>G (p.Leu200Trp) and c. 886_898delGGTAGCAGTGCTTinsCAGATAC (p.Gly296_Ser300delinsGlnIlePro). Protein structure analysis indicated that both variants are likely to be pathogenic. Sequencing of SLC25A3 should be considered in patients with isolated cardiomyopathy, even those without generalized skeletal myopathy or lactic acidosis.