Şeker Yilmaz, B;
Kör, D;
Bulut, FD;
Kilavuz, S;
Ceylaner, S;
Önenli Mungan, HN;
(2021)
Clinical and molecular findings in 37 Turkish patients with isolated methylmalonic acidemia.
Turkish Journal of Medical Sciences
10.3906/sag-2001-72.
(In press).
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Abstract
BACKGROUND/AIM: Isolated methylmalonic acidemia is caused by complete or partial deficiency of the enzyme methylmalonyl-CoA mutase (mut0 or mut? enzymatic subtype), a defect of its cofactor adenosyl-cobalamin (cblA, cblB, or cblD-MMA) or deficiency of the enzyme methylmalonyl-CoA epimerase. While onset of the disease ranges from the neonatal period to adulthood, most cases present with lethargy, vomiting and ketoacidosis in the early infancy. Major secondary complications are; growth failure, developmental delay, interstitial nephritis with progressive renal failure, basal ganglia injury and cardiomyopathy. We aimed to demonstrate clinical and molecular findings based on long-term follow up in our patient cohort. MATERIALS AND METHODS: The study includes 37 Turkish patients with isolated MMA who were followed up for long term complications 1 to 14 years. All patients were followed up regularly with clinical, biochemical and dietary monitoring to determine long term complications. Next Generation Sequencing technique was used for mutation screening in five disease-causing genes including; MUT, MMAA, MMAB, MMADHC, MCEE genes. Mutation screening identified 30 different types of mutations. RESULTS: While 28 of these mutations were previously reported, one novel MMAA mutation p.H382Pfs*24 (c.1145delA) and one novel MUT mutation IVS3+1G>T(c.752+1G>T) has been reported. The most common clinical complications were growth retardation, renal involvement, mental motor retardation and developmental delay. Furthermore, one of our patients developed cardiomyopathy, another one died because of hepatic failure and one presented with lactic acidosis after linezolid exposure. CONCLUSIONS: We have detected two novel mutations, including one splice-site mutation in the MUT gene and one frame shift mutation in the MMAA gene in 37 Turkish patients. We confirm the genotype-phenotype correlation in the study population according to the long term complications.
| Type: | Article |
|---|---|
| Title: | Clinical and molecular findings in 37 Turkish patients with isolated methylmalonic acidemia |
| Location: | Turkey |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3906/sag-2001-72 |
| Publisher version: | http://dx.doi.org/10.3906/sag-2001-72 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Methylmalonic acidemia, complications, novel mutations, outcome |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10119971 |
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