What is vitamin D-dependent rickets (type I)?

Answer

Also known as vitamin D–pseudodeficiency rickets (PDDR), this disorder results from a genetic deficiency in the enzyme that converts calcidiol to calcitriol in the kidney. Inheritance is autosomal recessive, and the gene is located in band 12q13.3. Clinical and laboratory examination findings are similar to those associated with nutritional rickets, with low levels of 1,25(OH)₂ vitamin D.

Levels of 1,25(OH)₂ vitamin D may be normal but inadequately low for the levels of calcium, phosphorus, and parathyroid hormone. These patients develop rickets despite receiving vitamin D at the recommended preventive doses.

Medical treatment consists of oral calcitriol (0.5-1.5mcg/day). These patients may also respond to pharmacologic doses of vitamin D (5,000-10,000U/day).

Did this answer your question?

Yes No

Additional feedback? (Optional)

Thank you for your feedback!

Michigami T. Skeletal mineralization: mechanisms and diseases. Ann Pediatr Endocrinol Metab. 2019 Dec. 24 (4):213-9. [Medline].
Martin A, David V, Laurence JS, et al. Degradation of MEPE, DMP1, and release of SIBLING ASARM-peptides (minhibins): ASARM-peptide(s) are directly responsible for defective mineralization in HYP. Endocrinology. 2008 Apr. 149(4):1757-72. [Medline].
Vieth R, Fraser D. Vitamin D insufficiency: no recommended dietary allowance exists for this nutrient. CMAJ. 2002 Jun 11. 166(12):1541-2. [Medline].
Chapman T, Sugar N, Done S, Marasigan J, Wambold N, Feldman K. Fractures in infants and toddlers with rickets. Pediatr Radiol. 2009 Dec 9. Epub:[Medline].
Tencza AL, Ichikawa S, Dang A, et al. Hypophosphatemic rickets with hypercalciuria due to mutation in SLC34A3/type IIc sodium-phosphate cotransporter: presentation as hypercalciuria and nephrolithiasis. J Clin Endocrinol Metab. 2009 Nov. 94(11):4433-8. [Medline]. [Full Text].
Henderson RC, Lin PP, Greene WB. Bone-mineral density in children and adolescents who have spastic cerebral palsy. J Bone Joint Surg Am. 1995 Nov. 77(11):1671-81. [Medline].
Hosseinpour F, Ellfolk M, Norlin M, Wikvall K. Phenobarbital suppresses vitamin D3 25-hydroxylase expression: a potential new mechanism for drug-induced osteomalacia. Biochem Biophys Res Commun. 2007 Jun 8. 357(3):603-7. [Medline].
Prie D, Huart V, Bakouh N, et al. Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter. N Engl J Med. 2002 Sep 26. 347(13):983-91. [Medline].
Florenzano P, Hartley IR, Jimenez M, Roszko K, Gafni RI, Collins MT. Tumor-induced osteomalacia. Calcif Tissue Int. 2020 Jun 5. [Medline].
Crysvita (burosumab) [package insert]. Novato, CA: Ultragenyx Pharmaceutical Inc. June 2020. Available at [Full Text].
FDA approves new treatment for rare metabolic disorder. U.S Food & Drug Administration. Available at https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm468836.htm. October 23, 2015; Accessed: March 28, 2017.
Whyte MP, Madson KL, Phillips D, Reeves AL, McAlister WH, Yakimoski A, et al. Asfotase alfa therapy for children with hypophosphatasia. JCI Insight. 2016 Jun 16. 1 (9):e85971. [Medline].
Plotkin H. Syndromes with congenital brittle bones. BMC Pediatr. 2004 Aug 31. 4:16. [Medline].
ADHR Consortium. Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet. 2000 Nov. 26(3):345-8. [Medline].
Anatoliotaki M, Tsilimigaki A, Tsekoura T, et al. Congenital rickets due to maternal vitamin D deficiency in a sunny island of Greece. Acta Paediatr. 2003. 92(3):389-91. [Medline].
Chesney RW, Zimmerman J, Hamstra A, et al. Vitamin D metabolite concentrations in vitamin D deficiency. Are calcitriol levels normal. Am J Dis Child. 1981 Nov. 135(11):1025-8. [Medline].
Intakes SCotSEoDR. Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press; 1997.
Juppner H. Novel regulators of phosphate homeostasis and bone metabolism. Ther Apher Dial. 2007. 11:S3-S22. [Medline].
Plotkin H, Lifshitz F. Rickets and osteoporosis. Lifshitz F, ed. Pediatric Endocrinology. 5th ed. 2006.

Media Gallery

Radiograph in a 4-year-old girl with rickets depicts bowing of the legs caused by loading.
Findings in patients with rickets.

of 2

Author

Horacio B Plotkin, MD, FAAP Chief Medical Officer, Retrophin, Inc; Adjunct Associate Professor of Pediatrics and Orthopedic Surgery, University of Nebraska College of Medicine

Horacio B Plotkin, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Received salary from PPD, Inc for: PPD.

Coauthor(s)

Laurence Finberg, MD Clinical Professor, Department of Pediatrics, University of California, San Francisco, School of Medicine and Stanford University School of Medicine

Laurence Finberg, MD is a member of the following medical societies: American Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Jatinder Bhatia, MBBS, FAAP Professor of Pediatrics, Medical College of Georgia, Georgia Regents University; Chief, Division of Neonatology, Director, Fellowship Program in Neonatal-Perinatal Medicine, Director, Transport/ECMO/Nutrition, Vice Chair, Clinical Research, Department of Pediatrics, Children's Hospital of Georgia

Jatinder Bhatia, MBBS, FAAP is a member of the following medical societies: Academy of Nutrition and Dietetics, American Academy of Pediatrics, American Association for the Advancement of Science, American Pediatric Society, American Society for Nutrition, American Society for Parenteral and Enteral Nutrition, Society for Pediatric Research, Southern Society for Pediatric Research

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Nestle<br/>Serve(d) as a speaker or a member of a speakers bureau for: Nestle<br/>Received income in an amount equal to or greater than $250 from: Nestle.

Acknowledgements

Maria Rebello Mascarenhas, MBBS Associate Professor of Pediatrics, University of Pennsylvania School of Medicine; Section Chief Nutrition, Division of Gastroenterology and Nutrition, Director, Nutrition Support Service, Children's Hospital of Philadelphia

Maria Rebello Mascarenhas, MBBS is a member of the following medical societies: American Gastroenterological Association, American Society for Parenteral and Enteral Nutrition, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

What is vitamin D-dependent rickets (type I)?

Answer

Related Questions:

References

Tables

Contributor Information and Disclosures