Abstract:
OBJECTIVE:To better delineate the natural history of patients with methylmalonic aciduria (MMA). STUDY DESIGN:Thirty patients with vitamin-B12-unresponsive MMA (25 aged 1.5 to 22.0 years (y) at the end of the study and 5 who died during a metabolic crisis) were managed following standardized guidelines and studied retrospectively. The median follow-up was 8.3 y (range: 1.4-19.5). Patients were investigated with neuropsychological testing, brain MRIs, inulin clearances, biochemical and genetic studies. RESULTS:Fifteen patients had a neonatal onset. Thirteen patients (43%) had significant neurological impairment. Chronic renal disease (CRD) occurred in 14 patients (47%) with a median age of onset of 6.5 y (range 1.5-18.6). Renal function further deteriorated in 4 patients within a median period of 5.8 y (range 2-7.4). Of 25 patients investigated at the enzymatic level, 17 were classified mut(o), 3 mut- and 5 cblA. Mortality, number of acute decompensations (p=0.031), median MMA urinary excretion (p=0.006) and neurological impairment (p<0.0001) were higher in mut degrees patients compared to mut-/cblA patients. Concerning the CRD, no difference incidence was found although the onset of CRD occurred earlier in mut(o) patients and was more severe. CONCLUSIONS:Our study provides unique data concerning the progression of renal disease in MMA. Patients with mut(o) phenotype have a more severe phenotype and probably an earlier and more severe CRD than patients with mut-/cblA phenotype.
journal_name
Mol Genet Metabjournal_title
Molecular genetics and metabolismauthors
Cosson MA,Benoist JF,Touati G,Déchaux M,Royer N,Grandin L,Jais JP,Boddaert N,Barbier V,Desguerre I,Campeau PM,Rabier D,Valayannopoulos V,Niaudet P,de Lonlay Pdoi
10.1016/j.ymgme.2009.03.006subject
Has Abstractpub_date
2009-07-01 00:00:00pages
172-8issue
3eissn
1096-7192issn
1096-7206pii
S1096-7192(09)00072-9journal_volume
97pub_type
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