Autosomal dominant hypophosphatemic rickets/osteomalacia

Clinical characterization of a novel renal phosphate-wasting disorder

Michael Econs, Paul T. McEnery

Research output: Contribution to journalArticle

206 Citations (Scopus)

Abstract

Renal phosphate-wasting disorders are the most common form of hereditary rickets and osteomalacia in western countries. Although autosomal dominant transmission of renal phosphate wasting has been described, previous studies included too few affected individuals to adequately characterize the disorder. We performed clinical and biochemical evaluations of individuals from a large kindred with autosomal dominant hypophosphatemic rickets/osteomalacia. We identified 23 affected members in this family, and for some individuals, follow-up was up to 25 yr. As patients were all members of the same kindred, we had the opportunity to determine the clinical manifestations of the disorder in patients who presumably all have the same genetic mutation. Affected individuals have isolated renal phosphate wasting and inappropriately normal serum calcitriol concentrations. The inheritance pattern was consistent with autosomal dominant transmission with variable penetrance. The family contained two subgroups of affected individuals. Group 1 consisted of patients who presented with renal phosphate wasting as adolescents or adults. These patients presented with bone pain, weakness, and insufficiency fractures, but did not manifest lower extremity deformity. Group 2 consisted of patients who presented with phosphate wasting, rickets, and lower extremity deformity as children. Surprisingly, some individuals in group 2 lost the renal phosphate-wasting defect after puberty. In conclusion, autosomal dominant hypophosphatemic rickets/osteomalacia is an inherited disorder of isolated renal phosphate wasting. The spectrum of disease includes delayed onset of penetrance and loss of the renal phosphate-wasting defect. Our results have implications in the evaluation of patients who present with renal phosphate wasting as either adults or children.

Original languageEnglish (US)
Pages (from-to)674-681
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume82
Issue number2
DOIs
StatePublished - 1997
Externally publishedYes

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Osteomalacia
Phosphates
Kidney
Rickets
Penetrance
Lower Extremity
Autosomal Dominant Hypophosphatemic Rickets
Inheritance Patterns
Defects
Stress Fractures
Calcitriol
Puberty
Bone
Bone and Bones
Pain
Mutation

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

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title = "Autosomal dominant hypophosphatemic rickets/osteomalacia: Clinical characterization of a novel renal phosphate-wasting disorder",
abstract = "Renal phosphate-wasting disorders are the most common form of hereditary rickets and osteomalacia in western countries. Although autosomal dominant transmission of renal phosphate wasting has been described, previous studies included too few affected individuals to adequately characterize the disorder. We performed clinical and biochemical evaluations of individuals from a large kindred with autosomal dominant hypophosphatemic rickets/osteomalacia. We identified 23 affected members in this family, and for some individuals, follow-up was up to 25 yr. As patients were all members of the same kindred, we had the opportunity to determine the clinical manifestations of the disorder in patients who presumably all have the same genetic mutation. Affected individuals have isolated renal phosphate wasting and inappropriately normal serum calcitriol concentrations. The inheritance pattern was consistent with autosomal dominant transmission with variable penetrance. The family contained two subgroups of affected individuals. Group 1 consisted of patients who presented with renal phosphate wasting as adolescents or adults. These patients presented with bone pain, weakness, and insufficiency fractures, but did not manifest lower extremity deformity. Group 2 consisted of patients who presented with phosphate wasting, rickets, and lower extremity deformity as children. Surprisingly, some individuals in group 2 lost the renal phosphate-wasting defect after puberty. In conclusion, autosomal dominant hypophosphatemic rickets/osteomalacia is an inherited disorder of isolated renal phosphate wasting. The spectrum of disease includes delayed onset of penetrance and loss of the renal phosphate-wasting defect. Our results have implications in the evaluation of patients who present with renal phosphate wasting as either adults or children.",
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