Methylmalonic aciduria as a biochemical marker for mitochondrial DNA depletion syndrome in patients with developmental delay and movement disorders: a case series

• DOI: 10.3389/fneur.2023.1265115
• Publication Date: 2023-11-24T13:44:45Z
• Authors: Montaha Almudhry; Arushi Gahlot Saini; Mohammed A. Al-Omari; Yashu Sharma; Maryam Nabavi Nouri; C. Anthony Rupar; Chitra Prasad; Andrea C. Yu; Savita Verma Attri; Asuri Narayan Prasad
• Keywords: Methylmalonic aciduria; Methylmalonic acidemia; Mitochondrial disease

Background Mitochondrial DNA (mtDNA) depletion syndromes (MDDS) are genetically and clinically variable disorders resulting from a reduction in mtDNA content the cells, tissues, organ systems, leading to symptoms related energy deficits. Deficiency of mitochondrial succinyl-CoA ligase/synthetase enzyme secondary pathogenic variations SUCLG1 SUCLA2 genes is subtype MDDS that presents with neurological manifestations specific biochemical profile. Methods This cross-sectional series describes five patients two tertiary care centers Canada India. Clinical data concerning course, investigations, outcome were gathered through chart reviews. Results All subjects presented early infancy manifestations, including movement disorder, psychomotor regression, developmental delay, hearing loss, behavioral issues, or combination thereof. Elevated methylmalonic acid metabolites, an abnormal acylcarnitine profile, lactic acidemia noted profile each patient ( n = 5/5, 100%). Molecular genetic testing disclosed presence homozygous mutations four compound heterozygosity one subject. Conclusion associated can be detected biochemically by aciduria besides elevation lactate, C3, C4DC, C5-OH acylcarnitine. Conducting metabolic workups MMA profiles heterogeneity clinical this marker may potentially reduce time diagnosis management.