Hypertrophic cardiomyopathy, cataract, developmental delay, lactic acidosis: a novel subtype of 3-methylglutaconic aciduria.
3-Methylglutaconic aciduria is the biochemical marker of several inherited metabolic diseases. Four types of 3-methylglutaconic aciduria can be distinguished. In the type I form, accumulation of 3-methylglutaconate is due to deficient activity of 3-methylglutaconyl-CoA hydratase, an enzyme of the leucine degradation pathway. In the other forms, 3-methylglutaconic acid is not derived from leucine but is of unidentified origin, possibly derived from other metabolic pathways, such as mevalonate metabolism. We report five patients, all presenting a severe early-onset phenotype characterized by 3-methylglutaconic aciduria, hypertrophic cardiomyopathy, cataract, hypotonia/developmental delay, lactic acidosis, and normal 3-methylglutaconyl-CoA hydratase activity. This peculiar phenotype, for which a primary mitochondrial disorder is hypothesized, identifies a novel subtype of 3-methylglutaconic aciduria.
Di Rosa
Gabriella
G
Division of Metabolism, Bambino Gesù Children's Research Hospital, Piazza S. Onofrio 4, I-00165, Rome, Italy.
Deodato
Federica
F
Loupatty
Ference J
FJ
Rizzo
Cristiano
C
Carrozzo
Rosalba
R
Santorelli
Filippo M
FM
Boenzi
Sara
S
D'Amico
Adele
A
Tozzi
Giulia
G
Bertini
Enrico
E
Maiorana
Andrea
A
Wanders
Ronald J A
RJ
Dionisi-Vici
Carlo
C
D000140:Acidosis, Lactic / Q000175:diagnosis*; D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis*; D001921:Brain / Q000378:metabolism; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis*; D002386:Cataract / Q000175:diagnosis*; D002658:Developmental Disabilities / Q000175:diagnosis*; D005192:Family Health; D005260:Female; D005977:Glutarates / Q000652:urine*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D010375:Pedigree
D005977:Glutarates; C022034:3-methylglutaconic acid