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Late-onset hereditary hypophosphatemic rickets with hypercalciuria (HHRH) due to mutation of SLC34A3/NPT2c.
Dhir, Gauri; Li, Dong; Hakonarson, Hakon; Levine, Michael A.
Afiliação
  • Dhir G; Division of Endocrinology Diabetes and Metabolism, Cooper Medical School of Rowan University, Camden, NJ 08103, USA.
  • Li D; Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • Hakonarson H; Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
  • Levine MA; Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA; Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. Electronic address: levinem@chop.edu.
Bone ; 97: 15-19, 2017 04.
Article em En | MEDLINE | ID: mdl-27939817
ABSTRACT

OBJECTIVE:

To identify a genetic basis for markedly reduced bone density and multiple fractures in an adult patient with hypophosphatemia and hypercalciuria.

SUBJECTS:

A 54-year-old Vietnamese man, his unaffected two daughters and wife.

METHODS:

We performed biochemical studies and sequenced the SLC34A3 gene using genomic DNA from peripheral blood mononuclear cells.

RESULTS:

Biochemical evaluation of the proband revealed hypophosphatemia with increased renal phosphate wasting, hypercalciuria, low serum parathyroid hormone (PTH) and an elevated serum 1,25(OH)2D level. Mutation analysis of SLC34A3 gene revealed that the patient was a compound heterozygote for two nonsynonymous nucleotide substitutions a novel c.571G>A (p.G191S) damaging mutation and the previously reported c.200G>A (p.R67H) polymorphism, consistent with the clinical diagnosis of late-onset hereditary hypophosphatemic rickets with hypercalciuria (HHRH). His wife and older daughter both carried the p.R67H polymorphism, while his younger daughter was compound heterozygous for p.R67H and p.G191S.

CONCLUSIONS:

HHRH is an uncommon autosomal recessive disease that generally manifests in childhood as rickets or nephrolithiasis, but an adult onset phenotype may occur in heterozygous carriers of SLC34A3 mutations. The severe presentation of this proband in adulthood with marked nephrolithiasis, multiple fractures and low bone density emphasizes the importance of measuring the serum phosphorus level in patients with suspected but unexplained osteoporosis and/or recurrent renal stones. The recognition of late-onset HHRH facilitates timely institution of appropriate therapy.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIc / Raquitismo Hipofosfatêmico Familiar / Hipercalciúria / Mutação Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Cotransportadoras de Sódio-Fosfato Tipo IIc / Raquitismo Hipofosfatêmico Familiar / Hipercalciúria / Mutação Idioma: En Ano de publicação: 2017 Tipo de documento: Article