Endocrinol Metab.  2014 Jun;29(2):195-201. 10.3803/EnM.2014.29.2.195.

A Novel PHEX Gene Mutation in a Patient with Sporadic Hypophosphatemic Rickets

Affiliations
  • 1Research Center for Endocrine and Metabolic Diseases, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea. kunsunkim@naver.com
  • 2Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea.

Abstract

Phosphate regulating gene with homologies to endopeptidases on the X-chromosome (PHEX) is a common cause of X-linked hypophosphatemic (XLH) rickets. Diverse PHEX gene mutations have been reported; however, gene mutations in sporadic rickets are less common than in XLH rickets. Herein, we describe a 50-year-old female patient with sporadic hypophosphatemic rickets harboring a novel splicing-site mutation in the PHEX gene (c.663+1G>A) at the exon 5-intron 5 boundary. The patient had recently suffered from right thigh pain and an aggravated waddling gait. She also presented with very short stature, generalized bone pain, and muscle weakness. Despite low serum phosphate levels, her phosphate reabsorption rate was lower than normal. Additionally, her 1,25-dihydroxyvitamin D3 concentration was lower than normal, although FGF23 level was normal. After treatment with alfacalcidol and elemental phosphate, her rachitic symptoms subsided, and callus formation was observed in the fracture site on the right femur.

Keyword

Phosphate regulating gene with homologies to endopeptidases on the X-chromosome; Rickets, hypophosphatemic; Fibroblast growth factor 23

MeSH Terms

Bony Callus
Calcitriol
Endopeptidases
Exons
Female
Femur
Gait
Humans
Middle Aged
Muscle Weakness
Rickets
Rickets, Hypophosphatemic*
Thigh
Calcitriol
Endopeptidases

Figure

  • Fig. 1 The plain films of the patient's long bones. Both humeri, femurs, tibias, and fibulas show anterolateral bowing. The arrow indicates the fracture line on the right metaphysis of the femur.

  • Fig. 2 Partial genomic DNA sequence of the PHEX gene. A heterozygote mutation within the splicing donor site, c.663+1G>A was found in the boundary of exon 5 and intron 5 on the PHEX gene.

  • Fig. 3 Whole body bone scan of the patient. A hot spot was found in the right femur fracture site and also in multiple pseudofractures in both lower extremities.

  • Fig. 4 After 2 months of alfacalcidol and elemental phosphate treatment, callus formation was observed in the fracture site on the right femur metaphysis.


Cited by  3 articles

A novel de novo mosaic mutation in PHEX in a Korean patient with hypophosphatemic rickets
Misun Yang, Jinsup Kim, Aram Yang, Jahyun Jang, Tae Yeon Jeon, Sung Yoon Cho, Dong-Kyu Jin
Ann Pediatr Endocrinol Metab. 2018;23(4):229-234.    doi: 10.6065/apem.2018.23.4.229.

Identification of a novel variant in the PHEX gene using targeted gene panel sequencing in a 24-month-old boy with hypophosphatemic rickets
Ha Young Jo, Jung Hyun Shin, Hye Young Kim, Young Mi Kim, Heirim Lee, Mi Hye Bae, Kyung Hee Park, Ja-Hyun Jang, Min Jung Kwak
Ann Pediatr Endocrinol Metab. 2020;25(1):63-67.    doi: 10.6065/apem.2020.25.1.63.

A pathogenic PHEX variant (c.1483-1G>C) in a Korean patient with X-linked hypophosphatemic rickets
In Hwa Jeong, Jae-Ho Yoo, Namhee Kim
Ann Pediatr Endocrinol Metab. 2021;26(2):130-133.    doi: 10.6065/apem.2040186.093.


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