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KMID : 0918520190190010012
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Journal of the Korean Society of Inherited Metabolic Disease
2019 Volume.19 No. 1 p.12 ~ p.19
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Somatic Cell Analysis and Cobalamin Responsiveness Study in Ten Korean Patients with Methylmalonic Aciduria
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Lim Han-Hyuk
Song Wung-Joo
Kim Gu-Hwan
Watkins David
Rosenblatt David S.
Kim Yoo-Mi
Chang Mea-Young
Kil Hong-Ryang
Kim Sook-Za
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Abstract
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Purpose: Isolated methylmalonic acidemia (MMA) is an autosomal recessive inherited disorder of propionate metabolism. There are two subtypes of MMUT gene defects. Mut0 represents complete loss of methylmalonyl-CoA mutase (MCM) activity while mut- is associated with residual MCM activity, which can be stimulated by hydroxocobalamin (OHCbl) supplementation. The objective of this study is to investigate cobalamin responsiveness and mutations present in Korean MMA population.
Methods: We evaluated 10 MMA patients using somatic cell complementation analysis on their fibroblasts to measure MCM activity and vitamin B12 responsiveness for the optimal treatment. MMUT gene was sequenced to identify the MMA mutations.
Results: For all patients, the incorporation of [14C]-propionate was low, and there was no response to OHCbl. The incorporation of [14C]-methyltetrahydrofolate and [57Co]-CNCbl fell within the normal range. There was adequate synthesis of methylcobalamin while the synthesis of adenosylcobalamin was low. The complementation analysis showed all patients were mut0. The sequence analysis identified 12 different MMUT mutations, including 2 novel mutations, p.Gln267Ter and p.Ile697Phe, were identified. All the patients in this study had neonatal onset of symptoms, belonged to mut0 complementation class, and as a result, showed no cobalamin responsiveness.
Conclusion: No Korean MMA patient showed cobalamin responsiveness.
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KEYWORD
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Methylmalonic acidemia, Methylmalonyl-CoA mutase, Mmut, Vitamin B12, Enzyme deficiency
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