Prediction of Outcome in Isolated Methylmalonic Acidurias: Combined Use of Clinical and Biochemical Parameters

Overview

Journal J Inherit Metab Dis

Publisher Wiley

Date 2009 Jul 31

PMID 19642010

Citations 33

Authors

F Horster

S F Garbade

T Zwickler

H I Aydin

O A Bodamer

A B Burlina

A M Das

J B C de Klerk

C Dionisi-Vici

S Geb

G Gokcay

N Guffon

E M Maier

E Morava

J H Walter

B Schwahn

F A Wijburg

M Lindner

S Grunewald

M R Baumgartner

S Kolker

Affiliations

Soon will be listed here.

Abstract

Objectives Isolated methylmalonic acidurias (MMAurias) are caused by deficiency of methylmalonyl-CoA mutase or by defects in the synthesis of its cofactor 5'-deoxyadenosylcobalamin. The aim of this study was to evaluate which parameters best predicted the long-term outcome. Methods Standardized questionnaires were sent to 20 European metabolic centres asking for age at diagnosis, birth decade, diagnostic work-up, cobalamin responsiveness, enzymatic subgroup (mut(0), mut(-), cblA, cblB) and different aspects of long-term outcome. Results 273 patients were included. Neonatal onset of the disease was associated with increased mortality rate, high frequency of developmental delay, and severe handicap. Cobalamin non-responsive patients with neonatal onset born in the 1970s and 1980s had a particularly poor outcome. A more favourable outcome was found in patients with late onset of symptoms, especially when cobalamin responsive or classified as mut(-). Prevention of neonatal crises in pre-symptomatically diagnosed newborns was identified as a protective factor concerning handicap. Chronic renal failure manifested earlier in mut(0) patients than in other enzymatic subgroups. Conclusion Outcome in MMAurias is best predicted by the enzymatic subgroup, cobalamin responsiveness, age at onset and birth decade. The prognosis is still unfavourable in patients with neonatal metabolic crises and non-responsiveness to cobalamin, in particular mut(0) patients.

Citing Articles

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Biomarkers to predict disease progression and therapeutic response in isolated methylmalonic acidemia.

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Different mutations in the MMUT gene are associated with the effect of vitamin B12 in a cohort of 266 Chinese patients with mut-type methylmalonic acidemia: A retrospective study.

Yu Y, Shuai R, Liang L, Qiu W, Shen L, Wu S Mol Genet Genomic Med. 2021; 9(11):e1822.

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