title: Clinical presentation and outcome in a series of 88 patients with the cblC defect.
abstract: The cblC defect is the most common inborn error of vitamin B12 metabolism. Despite therapeutic measures, the long-term outcome is often unsatisfactory. This retrospective multicentre study evaluates clinical, biochemical and genetic findings in 88 cblC patients. The questionnaire designed for the study evaluates clinical and biochemical features at both initial presentation and during follow up. Also the development of severity scores allows investigation of individual disease load, statistical evaluation of parameters between the different age of presentation groups, as well as a search for correlations between clinical endpoints and potential modifying factors.
  
  
  RESULTS
  No major differences were found between neonatal and early onset patients so that these groups were combined as an infantile-onset group representing 88 % of all cases. Hypotonia, lethargy, feeding problems and developmental delay were predominant in this group, while late-onset patients frequently presented with psychiatric/behaviour problems and myelopathy. Plasma total homocysteine was higher and methionine lower in infantile-onset patients. Plasma methionine levels correlated with "overall impression" as judged by treating physicians. Physician's impression of patient's well-being correlated with assessed disease load. We confirmed the association between homozygosity for the c.271dupA mutation and infantile-onset but not between homozygosity for c.394C>T and late-onset. Patients were treated with parenteral hydroxocobalamin, betaine, folate/folinic acid and carnitine resulting in improvement of biochemical abnormalities, non-neurological signs and mortality. However the long-term neurological and ophthalmological outcome is not significantly influenced. In summary the survey points to the need for prospective studies in a large cohort using agreed treatment modalities and monitoring criteria.
authors.affiliation: University Children's Hospital Basel, Spitalstrasse 33, Basel, 4506, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Fischer
authors.forename: Martina
authors.initials: M
authors.lastname: Huemer
authors.forename: Matthias
authors.initials: M
authors.lastname: Baumgartner
authors.forename: Federica
authors.initials: F
authors.lastname: Deodato
authors.forename: Diana
authors.initials: D
authors.lastname: Ballhausen
authors.forename: Avihu
authors.initials: A
authors.lastname: Boneh
authors.forename: Alberto B
authors.initials: AB
authors.lastname: Burlina
authors.forename: Roberto
authors.initials: R
authors.lastname: Cerone
authors.forename: Paula
authors.initials: P
authors.lastname: Garcia
authors.forename: Gülden
authors.initials: G
authors.lastname: Gökçay
authors.forename: Stephanie
authors.initials: S
authors.lastname: Grünewald
authors.forename: Johannes
authors.initials: J
authors.lastname: Häberle
authors.forename: Jaak
authors.initials: J
authors.lastname: Jaeken
authors.forename: David
authors.initials: D
authors.lastname: Ketteridge
authors.forename: Martin
authors.initials: M
authors.lastname: Lindner
authors.forename: Hanna
authors.initials: H
authors.lastname: Mandel
authors.forename: Diego
authors.initials: D
authors.lastname: Martinelli
authors.forename: Esmeralda G
authors.initials: EG
authors.lastname: Martins
authors.forename: Karl O
authors.initials: KO
authors.lastname: Schwab
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gruenert
authors.forename: Bernd C
authors.initials: BC
authors.lastname: Schwahn
authors.forename: László
authors.initials: L
authors.lastname: Sztriha
authors.forename: Maren
authors.initials: M
authors.lastname: Tomaske
authors.forename: Friedrich
authors.initials: F
authors.lastname: Trefz
authors.forename: Laura
authors.initials: L
authors.lastname: Vilarinho
authors.forename: David S
authors.initials: DS
authors.lastname: Rosenblatt
authors.forename: Brian
authors.initials: B
authors.lastname: Fowler
authors.forename: Carlo
authors.initials: C
authors.lastname: Dionisi-Vici
mesh_terms: D017668:Age of Onset; D001921:Brain / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005006:Ethnicity; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008661:Metabolism, Inborn Errors / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D010088:Oxidoreductases; D011379:Prognosis; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics*; D011795:Surveys and Questionnaires; D014805:Vitamin B 12 / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C508359:MMACHC protein, human; D010088:Oxidoreductases; D050721:Proto-Oncogene Proteins c-cbl; C119570:CBLC protein, human; D014805:Vitamin B 12