Clinical heterogeneity and prognosis in combined methylmalonic aciduria and homocystinuria (cblC)

The clbC form of methylmalonic acidaemia is a rare and poorly understood condition which results from impaired biosynthesis of methylcobalamin and adenosylcobalamin. The consequent functional deficiencies of methylmalonyl‐CoA mutase and methionine synthase produce both methylmalonic aciduria and hom...

Full description

Saved in:

Bibliographic Details
Published in:	Journal of inherited metabolic disease Vol. 20; no. 4; pp. 528 - 538
Main Authors:	Rosenblatt, D. S., Aspler, A. L., Shevell, M. I., Pletcher, B. A., Fenton, W. A., Seashore, M. R.
Format:	Journal Article
Language:	English
Published:	Dordrecht Kluwer Academic Publishers 01-08-1997 Springer
Subjects:	Adolescent Age of Onset Amino Acid Metabolism, Inborn Errors - genetics Amino Acid Metabolism, Inborn Errors - physiopathology Amino Acid Metabolism, Inborn Errors - urine Aminoacid disorders Biological and medical sciences Cause of Death Child Child, Preschool Errors of metabolism Female Genetic Complementation Test Homocystinuria - genetics Homocystinuria - physiopathology Homocystinuria - urine Humans Infant Infant, Newborn Male Medical sciences Metabolic diseases Methylmalonic Acid - blood Methylmalonic Acid - urine Nervous System Diseases - genetics Nervous System Diseases - physiopathology Phenotype Pregnancy Prognosis Treatment Outcome Human Nervous system diseases Prognosis Enzyme Deficiency Aciduria Metabolic diseases Enzymopathy Cerebral disorder Genetic disease Homocystinuria Phenotype Isomerases Association Methylmalonic acid Central nervous system disease Clinical biology Intramolecular transferases Evolution Clinical investigation Aminoacid disorder Methylmalonyl-CoA mutase
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The clbC form of methylmalonic acidaemia is a rare and poorly understood condition which results from impaired biosynthesis of methylcobalamin and adenosylcobalamin. The consequent functional deficiencies of methylmalonyl‐CoA mutase and methionine synthase produce both methylmalonic aciduria and homocystinuria. Systemic symptoms and neurological decompensation comprise the clinical phenotype. In an effort to clarify the phenotype and prognosis, we obtained clinical information on 50 patients with methylmalonic acidaemia whose cells had been assigned to the cblC complementation group. We identified two distinct phenotypes; they differed in age of onset, presence of systemic symptoms, type of neurological symptoms, and outcome after diagnosis and treatment. Forty‐four patients presented in the first year of life. Feeding difficulties, neurological dysfunction (hypotonia, seizures, developmental delay), and ophthalmological and haematological abnormalities characterized their clinical picture. About one‐quarter of those patients died. Survival was associated with neurological impairment; only one infant was neurologically intact at follow‐up. Onset in childhood, in contrast, was associated with less severe haematological abnormalities, largely involving the red cell series. Extrapyramidal signs, dementia, delirium or psychosis characterized the neurological findings. Survival, with mild to moderate disability in some, was typical in patients with later onset. Treatment in both groups included hydroxycobalamin, betaine and carnitine; complete normalization of biochemical parameters was rare.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0141-8955 1573-2665
DOI:	10.1023/A:1005353530303