Methylmalonic Aciduria Precision Panel
Methylmalonic Aciduria/Acidemia (MMA) is an autosomal recessive disorder of the amino acid metabolism with a defect localized in the conversion of methylmalonyl-coenzyme A (CoA) into succinyl-CoA.
Overview
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Methylmalonic Aciduria/Acidemia (MMA) is an autosomal recessive disorder of the amino acid metabolism with a defect localized in the conversion of methylmalonyl-coenzyme A (CoA) into succinyl-CoA. The body is therefore unable to process certain proteins and lipids properly. This causes an accumulation of methylmalonic acid in the organisms which manifests in the form of neurologic symptoms such as seizures, encephalopathy, and stroke. It is a lethal, severe heterogeneous disorder involving methylmalonate and cobalamin metabolism with poor prognosis. This disorder can be identified isolated or combined with other organic acidemias.
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The Igenomix Methylmalonic Aciduria Precision Panel can be used to make an accurate and directed diagnosis ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved.
Indication
- The Igenomix Methylmalonic Aciduria/Acidemia Precision Panel is indicated for those patients with a clinical suspicion or diagnosis with or without the following manifestations:
- Vomiting
- Dehydration
- Lethargy
- Seizures
- Recurrent infections
- Progressive encephalopathy
- Hypotonia
- Developmental delay
- Hepatomegaly
- Intellectual disability
Clinical Utility
The clinical utility of this panel is:
- The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient.
- The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient.
- Risk assessment and genetic counselling of asymptomatic family members according to the mode of inheritance.
- Improvement of delineation of genotype-phenotype correlation.
References
Sloan, J. L., Johnston, J. J., Manoli, I., Chandler, R. J., Krause, C., Carrillo-Carrasco, N., Chandrasekaran, S. D., Sysol, J. R., O’Brien, K., Hauser, N. S., Sapp, J. C., Dorward, H. M., Huizing, M., NIH Intramural Sequencing Center Group, Barshop, B. A., Berry, S. A., James, P. M., Champaigne, N. L., de Lonlay, P., Valayannopoulos, V., … Venditti, C. P. (2011). Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria. Nature genetics, 43(9), 883–886. https://doi.org/10.1038/ng.908
Matsui, S. M., Mahoney, M. J., & Rosenberg, L. E. (1983). The natural history of the inherited methylmalonic acidemias. New England Journal of Medicine, 308(15), 857-861. doi:10.1056/nejm198304143081501
Zhou, X., Cui, Y., & Han, J. (2018). Methylmalonic acidemia: Current status and research priorities. Intractable & rare diseases research, 7(2), 73–78. https://doi.org/10.5582/irdr.2018.01026
Deodato, F., Boenzi, S., Santorelli, F. M., & Dionisi-Vici, C. (2006). Methylmalonic and Propionic Aciduria. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 142C(2), 104-112. doi:10.1002/ajmg.c.30090
Miousse, I. R., Watkins, D., Coelho, D., Rupar, T., Crombez, E. A., Vilain, E., . . . Rosenblatt, D. S. (2009). Clinical and molecular heterogeneity in patients with the cbld inborn error of cobalamin metabolism. The Journal of Pediatrics, 154(4), 551-556. doi:10.1016/j.jpeds.2008.10.043
Carrillo-Carrasco, N., Chandler, R. J., & Venditti, C. P. (2011). Combined methylmalonic acidemia And homocystinuria, cblC type. I. Clinical Presentations, diagnosis and management. Journal of Inherited Metabolic Disease, 35(1), 91-102. doi:10.1007/s10545-011-9364-y
