Long-term outcome in methylmalonic aciduria: a series of 30 French patients.
OBJECTIVE
To better delineate the natural history of patients with methylmalonic aciduria (MMA).


METHODS
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.
Metabolic Center, Necker Enfants-Malades Hospital, Assistance-Publique-Hôpitaux de Paris, Paris, France.
M A
MA
Cosson
J F
JF
Benoist
G
G
Touati
M
M
Déchaux
N
N
Royer
L
L
Grandin
J P
JP
Jais
N
N
Boddaert
V
V
Barbier
I
I
Desguerre
P M
PM
Campeau
D
D
Rabier
V
V
Valayannopoulos
P
P
Niaudet
P
P
de Lonlay
D000293:Adolescent; D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications / Q000628:therapy* / Q000652:urine; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005602:France; D006801:Humans; D007223:Infant; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000473:pathology; D008297:Male; D008764:Methylmalonic Acid / Q000652:urine; D009422:Nervous System Diseases / Q000150:complications; D010641:Phenotype; D013997:Time Factors; D016896:Treatment Outcome; D044465:White People
D008764:Methylmalonic Acid