Genetic and enzymatic analysis for two Japanese patients with idiopathic infantile arterial calcification

J Bone Miner Metab. 2006;24(1):48-52. doi: 10.1007/s00774-005-0645-0.


Idiopathic infantile arterial calcification (IIAC) is a life-threatening disorder in young infants. Cardiovascular symptoms are usually apparent within the first month of life. The symptoms are caused by calcification of large and medium-sized arteries, including the aorta, coronary arteries, and renal arteries. Most of the patients die by 6 months of age because of heart failure. Recently, homozygous or compound heterozygous mutations for the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene were reported as causative for the disorder. ENPP1 regulates extracellular inorganic pyrophosphate (PPi), a major inhibiter of extracellular matrix calcification. Two Japanese patients with IIAC were studied. One, from first-cousin parents, showed a typical clinical course. The onset in the second patient was late. Both of the patients were clinically compatible for IIAC; arterial calcification was shown, and hypertension was prominent. We sequenced all the exons and exon-intron boundaries of the gene and measured nucleotide pyrophosphohydrolase (NPPH) activity of ENPP1. Homozygous Arg730Stop was detected in the typical IIAC patient. The mutation was a novel nonsense mutation and not detected in 60 healthy controls. His NPPH activity was 4% of normal. On the other hand, the late-onset patient was not shown to have any mutations. NPPH activity in this patient was 70% of normal. We confirmed that ENPP1 was also responsible for the Japanese patient with IIAC. The atypical late-onset phenotype may not be associated with ENPP1 abnormalities. IIAC is considered to be a clinically and genetically heterogeneous disorder.

Publication types

  • Case Reports

MeSH terms

  • Arteries
  • Calcinosis / enzymology
  • Calcinosis / genetics*
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Japan
  • Male
  • Mutation, Missense
  • Phosphoric Diester Hydrolases / genetics
  • Phosphoric Diester Hydrolases / metabolism*
  • Pyrophosphatases / genetics
  • Pyrophosphatases / metabolism*
  • Sequence Analysis, DNA
  • Vascular Diseases / enzymology
  • Vascular Diseases / genetics*


  • Phosphoric Diester Hydrolases
  • ectonucleotide pyrophosphatase phosphodiesterase 1
  • Pyrophosphatases