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

Area of Science:

• Genetics
• Mitochondrial Biology
• Neurology

Background:

• Mitochondrial phosphate carrier (PiC) deficiency, caused by SLC25A3 gene variants, is a rare autosomal recessive disorder.
• Typically presents in early childhood with hypertrophic cardiomyopathy (HCMP), hypotonia, and respiratory failure.

Purpose of the Study:

• To report a case of mitochondrial PiC deficiency with a later-onset phenotype.
• To expand the understanding of the clinical spectrum of SLC25A3-related disorders.

Main Methods:

• Clinical case presentation of a 32-year-old female with HCMP and myopathy.
• Muscle biopsy with histopathological analysis (COX, SDH activity).
• Genetic analysis identifying a homozygous splicing variant in the SLC25A3 gene.

Main Results:

• The patient presented with late-onset HCMP and myopathy, distinct from typical early-onset presentations.
• Muscle biopsy suggested mitochondrial myopathy with type 1 fiber predominance.
• Genetic confirmation of PiC deficiency due to SLC25A3 variant (NM_005888.4:c.158-9A>G).
• Persistent hyperlactatemia despite mitochondrial therapy and dietary changes.

Conclusions:

• This case expands the known clinical spectrum of mitochondrial PiC deficiency, demonstrating a later-onset phenotype.
• Highlights the importance of genetic testing for SLC25A3 variants in patients with unexplained HCMP and myopathy.
• Suggests ongoing monitoring for metabolic derangements like hyperlactatemia in affected individuals.