title: Changes in bone metabolic parameters following oral calcium supplementation in an adult patient with vitamin D-dependent rickets type 2A.
abstract: Vitamin D-dependent rickets type 2A (VDDR2A) is a rare inherited disorder with decreased tissue responsiveness to 1,25-dihydroxyvitamin D [1,25(OH)2D], caused by loss of function mutations in the vitamin D receptor (VDR) gene. Approximately 50 types of mutations have been identified so far that change amino acids in either the N-terminal DNA binding domain (DBD) or the C-terminal ligand binding domain (LBD) of the VDR protein. The degree of responsiveness to 1,25(OH)2D varies between patients with VDDR2A, which may depend on their residual VDR function. In this report, we describe a female patient with VDDR2A caused by an early stop codon (R30X) in the VDR gene that resulted in a severely truncated VDR protein. She developed alopecia and bowed legs within a year after birth and was diagnosed with rickets at the age of 2. She had been treated with active vitamin D and oral calcium supplementation until 22 years of age, when she developed secondary hyperparathyroidism and high bone turnover. The genetic diagnosis of VDDR2A promoted the discontinuation of active vitamin D treatment in favor of monotherapy with oral calcium supplementation. We observed amelioration of the secondary hyperparathyroidism and normalization of bone metabolic parameters within 6 years.
authors.affiliation: Division of Nephrology & Endocrinology, Department of Medicine, the University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kinoshita
authors.affiliation: Division of Nephrology & Endocrinology, Department of Medicine, the University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Ito
authors.affiliation: Division of Nephrology & Endocrinology, Department of Medicine, the University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Makita
authors.affiliation: Division of Nephrology & Endocrinology, Department of Medicine, the University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Nangaku
authors.affiliation: Fujii Memorial Institute of Medical Sciences, Tokushima University, Tokushima, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Fukumoto
mesh_terms: D000328:Adult; D000505:Alopecia / Q000209:etiology; D001842:Bone and Bones / Q000378:metabolism*; D002136:Calcium, Dietary / Q000627:therapeutic use*; D018388:Codon, Terminator; D019587:Dietary Supplements; D053098:Familial Hypophosphatemic Rickets / Q000178:diet therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000517:prevention & control; D009154:Mutation; D018167:Receptors, Calcitriol / Q000235:genetics; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D002136:Calcium, Dietary; D018388:Codon, Terminator; D018167:Receptors, Calcitriol; C579457:VDR protein, human
keywords: Calcium; Hyperparathyroidism; Rickets; Vitamin D receptor