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Marfanoid features in a child with combined methylmalonic aciduria and homocystinuria (CblC type)

  • Sandra G. Heil
  • Marije Hogeveen
  • Leo A. J. Kluijtmans
  • P. J. van Dijken
  • Gerard B. van de Berg
  • Henk J. Blom
  • Eva Morava
Short Report

Summary

Cobalamin is an essential cofactor for two mammalian enzymes: methionine synthase and methylmalonyl-CoA mutase. Patients with the cobalamin C (CblC) defect have combined methylmalonic aciduria and homocystinuria. Recently, the gene responsible for the CblC type, MMACHC, was identified, which enables molecular diagnostics. In this study, we describe two siblings, a 16-year-old girl and her 11-year-old brother, of a consanguineous family who presented with a very distinct clinical manifestation. The girl presented at the age of 13 years with macrocytic anaemia, cognitive regression and Marfanoid features such as increased arm-span, arachnodactyly, joint hyperlaxity and scoliosis. Her brother presented at the age of 10 months with developmental delay and behavioural abnormalities. Biochemical analysis showed severely increased homocysteine and methylmalonic acid levels in plasma of both siblings. In addition, plasma cysteine levels were decreased in the girl but not in her brother. The diagnosis of CblC defect was confirmed by genomic sequencing of the coding exons of the MMACHC gene. Two heterozygous mutations were identified in both siblings; the common c.271dupA p.Arg91LysfsX14 and a novel mutation, c.1A>G p.Met1?. Therapy consisting of folic acid, vitamin B6, l-carnitine and intramuscular vitamin B12 resulted in a clear improvement of biochemical parameters and, importantly, resulted in amelioration of the Marfanoid features in the girl. These data might suggest that low cysteine levels account for the Marfanoid features observed in the girl and indicate that the CblC type of combined methylmalonic aciduria and homocystinuria should be considered in the differential diagnosis of patients with Marfanoid features.

Keywords

Cobalamin Methylmalonic Homocystinuria Consanguineous Family Macrocytic Anaemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Supplementary material

10545_2007_Article_546_ESM.pdf (357 kb)
(PDF 357 Kb)

Copyright information

© SSIEM and Springer 2007

Authors and Affiliations

  • Sandra G. Heil
    • 1
  • Marije Hogeveen
    • 1
  • Leo A. J. Kluijtmans
    • 1
  • P. J. van Dijken
    • 2
  • Gerard B. van de Berg
    • 2
  • Henk J. Blom
    • 1
  • Eva Morava
    • 1
  1. 1.Department of Pediatrics, Laboratory of Pediatrics and NeurologyRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  2. 2.St Elisabeth HospitalTilburgThe Netherlands

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