Abstract
Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) was originally reported as a responsible gene for generalized arterial calcification in infancy (GACI). Though the prognosis of GACI patients is poor because of myocardial infarction and heart failure in relation to medial calcification of the coronary arteries, some patients rescued by bisphosphonate treatment have been reported. Recently, ENPP1 is also reported as responsible for autosomal recessive hypophosphatemic rickets type 2. We show here a boy with homozygous ENPP1 mutations diagnosed as having GACI in early infancy. After the diagnosis, he was treated with etidronate disodium (EHDP) in combination with antihypertensive drugs. The calcification of major arteries was diminished and disappeared by the age of eight months. He also showed mild hypophosphatemia (2.6–3.7mg/dl) from the age of one year. After the treatment with EHDP for five years, he showed genu valgum with hypophosphatemia (2.6mg/dl). He was diagnosed as having hypophosphatemic rickets at the age of seven years. The findings that hyper-mineralization of the arteries and hypo-mineralization of the bone observed in the same patient are noteworthy. ENPP1 could be regarded as a controller of the calcification of the whole body at least in part.
Highlights
Generalized arterial calcification of infancy (GACI; OMIM #208000) is a disorder characterized by medial calcification of elastic fibers in major arteries, such as aorta, renal arteries and coronary arteries, leading to angiostenosis throughout the body
This speculation is supported by the fact that there are no reports about recurrence of arterial calcification after cessation of etidronate disodium (EHDP) treatment in GACI patients except for one case whose arterial stenosis was worsened by calcitriol and phosphate supplementation (Otero et al, 2013; Rutsch et al, 2008; Numakura et al, 2006)
Hypophosphatemia and hypo-mineralization of the bone in GACI patients after infancy might be caused by FGF23 elevation resulted from progression of arterial calcification
Summary
Generalized arterial calcification of infancy (GACI; OMIM #208000) is a disorder characterized by medial calcification of elastic fibers in major arteries, such as aorta, renal arteries and coronary arteries, leading to angiostenosis throughout the body. Miyai et al / Bone Reports 3 (2015) 57–60 and antihypertensive drugs from the age of two months, and calcification of the arteries was disappeared by the age of eight months (Numakura et al, 2006) Afterwards he showed genu valgum with hypophosphatemia (2.7 – 3.7 mg/dl) at the age of five years and diagnosed as having hypophosphatemic rickets at the age of seven. We report his clinical course and discuss the role of ENPP1 in the mineralization in the bone and extra bone tissues
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