COMBINED MALONIC AND METHYLMALONIC ACIDURIA WITH EPILEPSY AND MOTOR DISORDERS IN A CHILD BORN FROM A CONSANGUINEOUS MARRIAGE
Keywords:
combined malonic and methylmalonic aciduria, ACSF3, organic acidurias, epileptic encephalopathy, whole-exome sequencing, inherited metabolic disordersAbstract
Combined malonic and methylmalonic aciduria (CMAMMA) is a rare inherited metabolic disorder caused by mutations in the ACSF3 gene. The disease is characterized by neurological impairment, developmental delay, epileptic seizures, and movement disorders. We present a clinical case of a 1.5-year-old child born from a consanguineous marriage with severe epileptic encephalopathy and significant neurological deficits. This case highlights the importance of comprehensive clinical, biochemical, and molecular genetic evaluation in the diagnosis of rare inherited metabolic disorders.
References
Alatibi Kh., Sumser K., Christopoulou M.E., Hug M.J., Tucci S. Dysregulated mitochondrial fission and neurodegeneration proteomic signature in ACSF3-deficient cells // Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. – 2025. – Vol. 1870, №2. – P. 159582.
Bowman C.E., Wolfgang M.J. Role of the malonyl-CoA synthetase ACSF3 in mitochondrial metabolism // Advances in Biological Regulation. – 2019. – Vol. 71. – P. 34–40.
Gragnaniello V., Galderisi A., Tucci S. et al. A Deep Clinical and Biochemical Characterization of a Patient With Combined Malonic and Methylmalonic Aciduria (CMAMMA) // JIMD Reports. – 2025. – Vol. 66, №6. – e70045.
Lee J.K., Oh A. Combined Malonic and Methylmalonic Aciduria Diagnosed by Recurrent and Severe Infections Mimicking a Primary Immunodeficiency Disease: A Case Report // Journal of Korean Medical Science. – 2023. – Vol. 38, №45. – e387.
Longo N., Frigeni M., Pasquali M. Carnitine transport and fatty acid oxidation // Biochimica et Biophysica Acta – Molecular Cell Research. – 2016. – Vol. 1863, №10. – P. 2422–2435.
Magoulas P.L., El-Hattab A.W. Systemic primary carnitine deficiency: an overview of clinical manifestations, diagnosis, and management // Orphanet Journal of Rare Diseases. – 2012. – Vol. 7. – P. 68.
Nowinski S.M., Solmonson A., Rusin S.F. et al. Mitochondrial fatty acid synthesis coordinates oxidative metabolism in mammalian mitochondria // eLife. – 2020. – Vol. 9. – e58041.
Stanley Ch.A. Carnitine Deficiency Disorders in Children // Annals of the New York Academy of Sciences. – 2009.
Tejero J., Lazure F., Gomes A.P. Methylmalonic acid in aging and disease // Trends in Endocrinology and Metabolism. – 2024. – Vol.
, №3. – P. 188–200.
Zou L., Yang Y., Wang Z. et al. Lysine Malonylation and Its Links to Metabolism and Diseases // Aging and Disease. – 2023. – Vol. 14,
№1. – P. 84–98.
