European Journal of Pediatrics

, Volume 173, Issue 12, pp 1707–1710 | Cite as

Reversible pulmonary arterial hypertension in cobalamin-dependent cobalamin C disease due to a novel mutation in the MMACHC gene

  • Mehmet Gündüz
  • Filiz Ekici
  • Eda Özaydın
  • Serdar Ceylaner
  • Belen Perez
Case Report


Methylmalonic aciduria and homocystinuria, cobalamin C (CblC) disease (OMIM 277400), is the most frequent inborn error of vitamin B12 (cobalamin, Cbl) metabolism and is caused by an inability of the cell to convert Cbl to its active forms (MeCbl and AdoCbl). More than 75 mutations have been identified in the MMACHC gene which is responsible for CblC disease. We present a case with CblC disease and pulmonary arterial hypertension (PAH) as the main symptom. The patient improved dramatically with parenteral hydroxocobalamin treatment. Most cases of CblC disease have a multisystemic disease with failure to thrive, developmental delay, hypotonia, visual impairment, and hematologic manifestations. This patient had isolated pulmonary hypertension and hyperhomocysteinemia which is thought to be an important factor in the pathogenesis of PAH. Genetic analysis identified a novel homozygous mutation (c.484G > T; p.Gly162Trp) in the MMACHC gene. Conclusion: CblC disease should be considered in the differential diagnosis of pulmonary hypertension.


Cobalamin C disease Pulmonary hypertension 



Adenosyl cobalamin


Cobalamin C




Hemolytic uremic syndrome


Methyl cobalamin


Methymalonic acid




Pulmonary arterial hypertension


Conflict of interest

Dr. Gündüz, Dr. Ekici, Dr. Özaydın, Dr. Ceylaner, and Dr. Perez declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Mehmet Gündüz
    • 1
  • Filiz Ekici
    • 2
  • Eda Özaydın
    • 3
  • Serdar Ceylaner
    • 4
  • Belen Perez
    • 5
  1. 1.Division of Nutrition and Metabolism, Ministry of HealthAnkara Children’s Health and Diseases, Hematology-Oncology HospitalAnkaraTurkey
  2. 2.Department of Pediatric Cardiology, Ministry of HealthAnkara Children’s Health and Diseases, Hematology-Oncology HospitalAnkaraTurkey
  3. 3.Infancy Service, Ministry of HealthAnkara Children’s Health and Diseases, Hematology-Oncology HospitalAnkaraTurkey
  4. 4.Ankara Intergen LaboratoryAnkaraTurkey
  5. 5.Department of Biochemistry and Molecular BiologyMadrid Auto UniversityMadridSpain

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