Abstract
Defects in the human gene encoding methylmalonyl-CoA mutase enzyme (MCM) give rise to a rare autosomal recessive inherited disorder of propionate metabolism termed mut methylmalonic acidemia (MMA). Patients with mut MMA have been divided into two subgroups: mut0 with complete loss of MCM activity and mut- with residual activity in the presence of adenosylcobalamin (AdoCbl). The disease typically presents in the first weeks or months of life and is clinically characterized by recurrent vomiting, metabolic acidosis, hyperammonemia, lethargy, poor feeding, failure to thrive and neurological deficit. To better elucidate the spectrum of mutations causing mut MMA in Saudi patients, we screened a cohort of 60 Saudi patients affected by either forms of the disease for mutations in the MUT gene. A total of 13 different mutations, including seven previously reported missense changes and six novel mutations, were detected in a homozygous state except for two compound heterozygous cases. The six novel mutations identified herein consist of three nonsense, two missense and one frameshift, distributed throughout the whole protein. This study describes for the first time the clinical and mutational spectrum of mut MMA in Saudi Arabian patients.
Competing interests: None declared
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Acknowledgements
The authors would like to thank the patients and their families for participating in this study and the KFSH&RC Department of Genetics Sequencing Core Facility. This work was funded by the King Faisal Specialist Hospital and Research Centre (RAC# 2020 011).
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Communicated by: Ivo Barić, M.D., PhD, Professor of Pediatrics
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Informed Consent: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients being included in the study.
FI, BAM, AM, MH and RA performed molecular genetic studies, analysis and interpretation. ZH, MO, HZ, ZR, AQ, EF, AA, FM, MF, WE, MS and MAS provided patient information, clinical diagnosis and samples and were involved in data interpretation. All authors were all involved in drafting and revising the article.
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Imtiaz, F. et al. (2014). Spectrum of Mutations in 60 Saudi Patients with Mut Methylmalonic Acidemia. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 29. JIMD Reports, vol 29. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_297
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DOI: https://doi.org/10.1007/8904_2014_297
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