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.
Department of General Pediatrics, Division of Inborn
Metabolic Diseases, University Children's Hospital, D-69120
Heidelberg, Germany.
Friederike.Hoerster@med.uni-heidelberg.de
%0 Journal Article
%1 hörster.baumgartner.ea:long-term
%A Hörster, Friederike
%A Baumgartner, Matthias R
%A Viardot, Caroline
%A Suormala, Terttu
%A Burgard, Peter
%A Fowler, Brian
%A Hoffmann, Georg F
%A Garbade, Sven F
%A Kölker, Stefan
%A Baumgartner, E. Regula
%D 2007
%J Pediatr Res
%K 12, Acid Acid, Adolescent; Adult; Age Alkyl Amino Aryl B Child; Chronic, Cobamides, Complex, Disease Disease; Diseases, Errors, Estimate; Factors; Failure, Female; Follow-Up Gastrointestinal Genetic Humans; Inborn Kaplan-Meiers Kidney Male; Membrane Metabolism, Methylmalonic Methylmalonyl-CoA Mitochondrial Mutase, Mutation; Nervous Onset; Predisposition Prognosis; Progression; Prospective Proteins, Studies; System Time Transferases, Transport Vitamin and complications/drug etiology; genetics/metabolism; metabolism/urine; metabolism; of sfg therapeutic therapy/enzymology/genetics/mortality; to use use;
%N 2
%P 225--230
%R 10.1203/PDR.0b013e3180a0325f
%T Long-term outcome in methylmalonic acidurias is influenced
by the underlying defect (mut0, mut-, cblA, cblB).
%U http://dx.doi.org/10.1203/PDR.0b013e3180a0325f
%V 62
%X 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.
@article{hörster.baumgartner.ea:long-term,
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.},
added-at = {2017-04-01T10:34:58.000+0200},
author = {Hörster, Friederike and Baumgartner, Matthias R and Viardot, Caroline and Suormala, Terttu and Burgard, Peter and Fowler, Brian and Hoffmann, Georg F and Garbade, Sven F and Kölker, Stefan and Baumgartner, E. Regula},
biburl = {https://www.bibsonomy.org/bibtex/21522da3ab2b60a986d4d9e8f60d140c6/sveng},
doi = {10.1203/PDR.0b013e3180a0325f},
institution = {Department of General Pediatrics, Division of Inborn
Metabolic Diseases, University Children's Hospital, D-69120
Heidelberg, Germany.
Friederike.Hoerster@med.uni-heidelberg.de},
interhash = {6c68c046ab9cd5acb0ed96d20d8ef5f8},
intrahash = {1522da3ab2b60a986d4d9e8f60d140c6},
journal = {Pediatr Res},
keywords = {12, Acid Acid, Adolescent; Adult; Age Alkyl Amino Aryl B Child; Chronic, Cobamides, Complex, Disease Disease; Diseases, Errors, Estimate; Factors; Failure, Female; Follow-Up Gastrointestinal Genetic Humans; Inborn Kaplan-Meiers Kidney Male; Membrane Metabolism, Methylmalonic Methylmalonyl-CoA Mitochondrial Mutase, Mutation; Nervous Onset; Predisposition Prognosis; Progression; Prospective Proteins, Studies; System Time Transferases, Transport Vitamin and complications/drug etiology; genetics/metabolism; metabolism/urine; metabolism; of sfg therapeutic therapy/enzymology/genetics/mortality; to use use;},
month = Aug,
number = 2,
owner = {sfg},
pages = {225--230},
pmid = {17597648},
timestamp = {2017-04-01T10:35:16.000+0200},
title = {Long-term outcome in methylmalonic acidurias is influenced
by the underlying defect (mut0, mut-, cblA, cblB).},
url = {http://dx.doi.org/10.1203/PDR.0b013e3180a0325f},
volume = 62,
year = 2007
}