Prediction of outcome in isolated methylmalonic acidurias: combined use of clinical and biochemical parameters.
Objectives Isolated methylmalonic acidurias (MMAurias) are caused by deficiency of methylmalonyl-CoA mutase or by defects in the synthesis of its cofactor 5'-deoxyadenosylcobalamin. The aim of this study was to evaluate which parameters best predicted the long-term outcome. Methods Standardized questionnaires were sent to 20 European metabolic centres asking for age at diagnosis, birth decade, diagnostic work-up, cobalamin responsiveness, enzymatic subgroup (mut(0), mut(-), cblA, cblB) and different aspects of long-term outcome. Results 273 patients were included. Neonatal onset of the disease was associated with increased mortality rate, high frequency of developmental delay, and severe handicap. Cobalamin non-responsive patients with neonatal onset born in the 1970s and 1980s had a particularly poor outcome. A more favourable outcome was found in patients with late onset of symptoms, especially when cobalamin responsive or classified as mut(-). Prevention of neonatal crises in pre-symptomatically diagnosed newborns was identified as a protective factor concerning handicap. Chronic renal failure manifested earlier in mut(0) patients than in other enzymatic subgroups. Conclusion Outcome in MMAurias is best predicted by the enzymatic subgroup, cobalamin responsiveness, age at onset and birth decade. The prognosis is still unfavourable in patients with neonatal metabolic crises and non-responsiveness to cobalamin, in particular mut(0) patients.
Hörster
F
F
Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany. friederike.hoerster@med.uni-heidelberg.de.
Garbade
S F
SF
Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
Zwickler
T
T
Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
Aydin
H I
HI
Department of Metabolism, Children's Hospital, Hacettepe University Ankara, Ankara, Turkey.
Bodamer
O A
OA
Department of Paediatrics, Allgemeines Krankenhaus, Vienna, Austria.
Burlina
A B
AB
Department of Paediatrics, Division of Metabolic Disorders, University Hospital Padova, Padova, Italy.
Das
A M
AM
Department of Paediatrics II, Medizinische Hochschule Hannover, Hannover, Germany.
De Klerk
J B C
JBC
Sophia Children's Hospital, Erasmus Medical Centre, Rotterdam, The Netherlands.
Dionisi-Vici
C
C
Division of Metabolism, Bambino Gesù Children's Hospital, Rome, Italy.
Geb
S
S
University Children's Hospital I, Frankfurt, Germany.
Gökcay
G
G
Department of Nutrition and Metabolism, Istanbul University Medical Faculty Children's Hospital, Istanbul, Turkey.
Guffon
N
N
Centre de Référence des Maladies Héréditaires du Métabolisme, Hôpital Femme Mère Enfant, Lyon, France.
Maier
E M
EM
Dr. von Hauner Children's Hospital, Munich, Germany.
Morava
E
E
Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands.
Walter
J H
JH
Willink Unit, Royal Manchester Children's Hospital, Manchester, UK.
Schwahn
B
B
Department of General Pediatrics, University Children's Hospital, Düsseldorf, Germany.
Wijburg
F A
FA
Department of Pediatrics, Academic Medical Centre, University Hospital, Amsterdam, The Netherlands.
Lindner
M
M
Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
Grünewald
S
S
Metabolic Unit, Great Ormond Street Hospital, London, UK.
Baumgartner
M R
MR
Metabolism and Molecular Paediatrics, University Children's Hospital, Zurich, Switzerland.
Kölker
S
S
Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children's Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120, Heidelberg, Germany.
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics / Q000401:mortality; D015415:Biomarkers / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D003038:Cobamides / Q000172:deficiency; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008765:Methylmalonyl-CoA Mutase / Q000172:deficiency* / Q000235:genetics; D017063:Outcome Assessment, Health Care; D011379:Prognosis; D016019:Survival Analysis; D055815:Young Adult
D015415:Biomarkers; D003038:Cobamides; D008765:Methylmalonyl-CoA Mutase; C000913:cobamamide