Long-term outcome in methylmalonic acidurias is influenced by the underlying defect (mut0, mut-, cblA, cblB).

Abstract

Isolated methylmalonic acidurias comprise a heterogeneous group of inborn errors of metabolism caused by defects of methylmalonyl-CoA mutase (MCM) (mut0, mut-) or deficient synthesis of its cofactor 5'-deoxyadenosylcobalamin (AdoCbl) (cblA, cblB). The aim of this study was to compare the long-term outcome in patients from these four enzymatic subgroups. Eighty-three patients with isolated methylmalonic acidurias (age 7-33 y) born between 1971 and 1997 were enzymatically characterized and prospectively followed to evaluate the long-term outcome (median follow-up period, 18 y). Patients with mut0 (n = 42), mut- (n = 10), cblA (n = 20), and cblB (n = 11) defects were included into the study. Thirty patients (37%) died, and 26 patients survived with a severe or moderate neurologic handicap (31%), whereas 27 patients (32%) remained neurologically uncompromised. Chronic renal failure (CRF) was found most frequently in mut0 (61%) and cblB patients (66%), and was predicted by the urinary excretion of methylmalonic acid (MMA) before CRF. Overall, patients with mut0 and cblB defects had an earlier onset of symptoms, a higher frequency of complications and deaths, and a more pronounced urinary excretion of MMA than those with mut- and cblA defects. In addition, long-term outcome was dependent on the age cohort and cobalamin responsiveness.

• Authors: Friederike Hörster, Matthias R Baumgartner, Caroline Viardot, Terttu Suormala, Peter Burgard, Brian Fowler, Georg F Hoffmann, Sven F Garbade, Stefan Kölker, E Regula Baumgartner
• Journal: Pediatric research (Pediatr Res) Vol. 62 Issue 2 Pg. 225-30 (Aug 2007) ISSN: 0031-3998 [Print] United States
• PMID: 17597648 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cobamides
• MMAA protein, human
• Membrane Transport Proteins
• Mitochondrial Membrane Transport Proteins
• Mitochondrial Proteins
• Vitamin B Complex
• Methylmalonic Acid
• Alkyl and Aryl Transferases
• cob(I)alamin adenosyltransferase
• Methylmalonyl-CoA Mutase
• cobamamide
• Vitamin B 12

Topics

• Adolescent
• Adult
• Age of Onset
• Alkyl and Aryl Transferases (genetics, metabolism)
• Amino Acid Metabolism, Inborn Errors (complications, drug therapy, enzymology, genetics, mortality)
• Child
• Cobamides (metabolism)
• Disease Progression
• Female
• Follow-Up Studies
• Gastrointestinal Diseases (etiology)
• Genetic Predisposition to Disease
• Humans
• Kaplan-Meier Estimate
• Kidney Failure, Chronic (etiology)
• Male
• Membrane Transport Proteins (genetics, metabolism)
• Methylmalonic Acid (metabolism, urine)
• Methylmalonyl-CoA Mutase (genetics, metabolism)
• Mitochondrial Membrane Transport Proteins
• Mitochondrial Proteins (genetics, metabolism)
• Mutation
• Nervous System Diseases (etiology)
• Prognosis
• Prospective Studies
• Time Factors
• Vitamin B 12 (therapeutic use)
• Vitamin B Complex (therapeutic use)