eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Hypophosphatemic Rickets: Differential Diagnoses & Workup

Author: Karl S Roth, MD, Professor and Chair, Department of Pediatrics, Creighton University School of Medicine
Coauthor(s): James CM Chan, MD, Professor of Pediatrics, University of Vermont College of Medicine; Director of Research, The Barbara Bush Children's Hospital, Maine Medical Center
Contributor Information and Disclosures

Updated: Feb 6, 2009

Differential Diagnoses

Cystinosis
Fanconi Syndrome
Tyrosinemia

Other Problems to Be Considered

Renal tubular acidosis
Hereditary hypophosphatemic rickets with hypocalciuria
Fanconi syndrome (types I and II)
Vitamin D-dependent rickets (types I and II)
Vitamin D-deficient rickets
Pseudohypoparathyroidism

Workup

Laboratory Studies

  • Begin clinical laboratory evaluation of rickets with assessment of serum calcium, phosphate, and alkaline phosphatase levels.
  • In hypophosphatemic rickets, calcium levels may be within or slightly below the reference range; alkaline phosphatase levels are significantly above the reference range.
  • Carefully evaluate serum phosphate levels in the first year of life because the concentration reference range for infants (5.0-7.5 mg/dL) is high compared with adults (2.7-4.5 mg/dL). Hypophosphatemia can easily be missed in a baby.
  • Serum parathyroid hormone levels are within the reference range or slightly elevated, while calcitriol levels are low or within the lower reference range.
  • Most importantly, urinary loss of phosphate is above the reference range.

Imaging Studies

  • In all cases of rickets, the study of choice is radiography of the wrists, knees, ankles, and long bones. No pathognomonic sign on radiographs distinguishes hypophosphatemic rickets from any other etiology.
  • In children receiving treatment, periodic renal ultrasonography studies are important to monitor for development of nephrocalcinosis. Originally thought to be a sequela of the disease, this complication is now recognized as an iatrogenic result of therapy. Monitoring the ratio of calcium to creatinine in the urine is also important. A ratio of more than 0.25:1 requires reduction of the vitamin D dosage to avoid nephrocalcinosis.

Other Tests

  • Renal tubular phosphate reabsorption
    • The renal tubular reabsorption of phosphate (TRP) is calculated with the following formula:

      1 - [Phosphate Clearance (CPi) / Creatinine Clearance (Ccr)] X 100
    • The following formula calculates CPi:

      [Urine Phosphate (mg/dL) X Volume (mL/min)] / Plasma Phosphate (mg/dL)  
    • By substituting creatinine values for phosphate in the same formula, Ccr can also be calculated.
    • A single, early-morning urine sample can be used because CPi divided by Ccr causes units of urine volume to cancel each other.
    • The TRP in X-linked hypophosphatemia is 60%; normal TRP exceeds 90% at the same reduced plasma phosphate concentration.

More on Hypophosphatemic Rickets

Overview: Hypophosphatemic Rickets
Differential Diagnoses & Workup: Hypophosphatemic Rickets
Treatment & Medication: Hypophosphatemic Rickets
Follow-up: Hypophosphatemic Rickets
References
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References

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  2. Alon US, Monzavi R, Lilien M, et al. Hypertension in hypophosphatemic rickets--role of secondary hyperparathyroidism. Pediatr Nephrol. Feb 2003;18(2):155-8. [Medline].

  3. Ariceta G, Langman CB. Growth in X-linked hypophosphatemic rickets. Eur J Pediatr. Apr 2007;166(4):303-9. [Medline].

  4. Baroncelli GI, Federico G, Bertelloni S, et al. Assessment of bone quality by quantitative ultrasound of proximal phalanges of the hand and fracture rate in children and adolescents with bone and mineral disorders. Pediatr Res. Jul 2003;54(1):125-36. [Medline].

  5. Baum M, Syal A, Quigley R, Seikaly M. Role of prostaglandins in the pathogenesis of X-linked hypophosphatemia. Pediatr Nephrol. Aug 2006;21(8):1067-74. [Medline].

  6. Blackard WG, Robinson RR, White JE. Familial hypophosphatemia. Report of a case, with observations regarding pathogenesis. Nord Hyg Tidskr. May 3 1962;266:899-905. [Medline].

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  15. Miller PD, McClung MR, Macovei L, et al. Monthly oral ibandronate therapy in postmenopausal osteoporosis: 1- year results from the MOBILE study. J Bone Miner Res. Aug 2005;20(8):1315-1322. [Medline].

  16. Petersen DJ, Boniface AM, Schranck FW. X-linked hypophosphatemic rickets: a study (with literature review) of linear growth response to calcitriol and phosphate therapy. J Bone Miner Res. Jun 1992;7(6):583-97. [Medline].

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  18. Quarles LD. FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization. Am J Physiol Endocrinol Metab. Jul 2003;285(1):E1-9. [Medline].

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  21. Sochett E, Doria AS, Henriques F, et al. Growth and metabolic control during puberty in girls with X-linked hypophosphataemic rickets. Horm Res. 2004;61(5):252-6. [Medline].

  22. Stickler GB, Morgenstern BZ. Hypophosphataemic rickets: final height and clinical symptoms in adults. Lancet. Oct 14 1989;2(8668):902-5. [Medline].

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Further Reading

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Keywords

hypophosphatemic rickets, familial hypophosphatemic rickets, vitamin D-resistant rickets, X-linked hypophosphatemic rickets, X-linked hypophosphatemic osteomalacia, rachitic disease, vitamin D ingestion, vitamin D–resistant rickets, hypophosphatemia, proteolysis, hyperphosphaturia, short stature, dental abscess, delayed dentition, bone deformation, cranial synostosis, short stature

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Contributor Information and Disclosures

Author

Karl S Roth, MD, Professor and Chair, Department of Pediatrics, Creighton University School of Medicine
Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Clinical Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

Coauthor(s)

James CM Chan, MD, Professor of Pediatrics, University of Vermont College of Medicine; Director of Research, The Barbara Bush Children's Hospital, Maine Medical Center
James CM Chan, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Association of University Professors, American Chemical Society, American Heart Association, American Medical Association, American Physiological Society, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Pediatric Nephrology, International Society of Nephrology, New York Academy of Sciences, Society for Experimental Biology and Medicine, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Arlan L Rosenbloom, MD, Adjunct Distinguished Service Professor Emeritus of Pediatrics, University of Florida; Fellow of the American Academy of Pediatrics; Fellow of the American College of Epidemiology
Arlan L Rosenbloom, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Epidemiology, American Pediatric Society, Endocrine Society, Florida Pediatric Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London), Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Greece
George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Endocrinology, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences
Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Lawson-Wilkins Pediatric Endocrine Society
Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD, Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas and Arkansas Children's Hospital
Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research
Disclosure: Genentech, Inc. Honoraria Speaking and teaching; Pfiser, Inc. Honoraria Consulting

 
 
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