title: Hypophosphatemic rickets developed after treatment with etidronate disodium in a patient with generalized arterial calcification in infancy.
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,ENPP1is also reported as responsible for autosomal recessive hypophosphatemic rickets type 2. We show here a boy with homozygousENPP1mutations 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 (2.6-3.7 mg/dl) from the age of one year. After the treatment with EHDP for five years, he showed genu valgum with hypophosphatemia (2.6 mg/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.ENPP1could be regarded as a controller of the calcification of the whole body at least in part.
authors.affiliation: Division of Endocrinology and Metabolism, Tokyo Metropolitan Children's Medical Center, 2-8-29 Musashidai, Fuchu, Tokyo 183-8561, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Miyai
authors.affiliation: Division of Developmental Genetics, Institute of Resource Development and Analysis, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ariyasu
authors.affiliation: Department of Pediatrics, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan.
authors.forename: Chikahiko
authors.initials: C
authors.lastname: Numakura
authors.affiliation: Department of Pediatrics, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Yoneda
authors.affiliation: Department of Pediatrics, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakazato
authors.affiliation: Division of Endocrinology and Metabolism, Tokyo Metropolitan Children's Medical Center, 2-8-29 Musashidai, Fuchu, Tokyo 183-8561, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Hasegawa
keywords: ARHR2, autosomal recessive hypophosphatemic rickets type 2; EHDP, etidronate disodium; ENPP1, ectonucleotide pyrophosphatase/phosphodiesterase 1; Ectonucleotide pyrophosphatase/phosphodiesterase 1; Etidronate disodium; GACI, Generalized arterial calcification of infancy; Generalized arterial calcification of infancy; Hypophosphatemic rickets; NPPH, nucleotide pyrophosphohydrolase; PPi, inorganic pyrophosphate; VSMCs, vascular smooth muscle cells