title: Vitamin D-dependent rickets type 1: a rare, but treatable, cause of severe hypotonia in infancy.
abstract: Vitamin D-dependent rickets type 1 is an autosomal recessive disorder caused by an inactivating mutation of the 25-hydroxyvitamin-D-1α-hydroxylase (CYP27B1) gene. Clinical presentation is characterized by early onset of severe rickets and can include severe hypotonia. Here, we report a 16-month-old white male who presented with severe muscle weakness, failure to thrive, renal tubular dysfunction, and skeletal deformities, including osteopenia and multiple fractures. At presentation, he had severe hypocalcemia, hypophosphatemia, hypomagnesemia, and elevated alkaline phosphatase and parathyroid hormone levels, although normal 25-hydroxyvitamin D levels. DNA sequencing of the CYP27B1 gene revealed a novel mutation in exon 2 (c286_300de115) and a previously reported mutation in exon 7 (c.1166G>A). Once calcitriol therapy was initiated, the patient showed significant improvement in muscle strength and linear growth. Serum calcium, phosphorous, and alkaline phosphatase returned to normal range. Organic aciduria resolved and aminoaciduria significantly improved 2 months after parathyroid hormone levels normalized.
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yan
authors.forename: Ali S
authors.initials: AS
authors.lastname: Calikoglu
authors.forename: Nina
authors.initials: N
authors.lastname: Jain
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics; D002658:Developmental Disabilities / Q000209:etiology; D006801:Humans; D007223:Infant; D007674:Kidney Diseases / Q000209:etiology; D008297:Male; D009123:Muscle Hypotonia / Q000209:etiology*; D012279:Rickets / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000150:complications / Q000188:drug therapy* / Q000235:genetics
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase