ESPE Abstracts (2016) 86 P-P2-166

Diversity in Phenotype of Two Siblings and their with X-Linked Hypophosphatemic Rickets due to PHEX Mutation

Aleksandra Rojeka, Zofia Kolesinskab & Marek Niedzielaa,c


aPoznan University of Medical Sciences, Department of Pediatric Endocrinology and Rheumatology, Molecular Endocrinology Laboratory, Poznan, Poland; bPoznan University of Medical Sciences, Department of Pediatric Endocrinology and Rheumatology, Poznan, Poland; cKarol Jonscher’s Clinical Hospital, Poznan, Poland


Background: Hypophosphatemic rickets (HR) is a group of rare disorders caused by an excessive renal phosphate wasting. The dominant form of X-linked HR (XLHR) is caused by mutation in PHEX (phosphate-regulating endopeptidase) gene. XLHR phenotype is characterized mainly by rickets, bone deformities, short stature, dental anomalies, hypophosphatemia, low renal phosphate reabsorption, normal serum calcium level, hypocalciuria, normal/low serum level of vitamin D (1,25(OH)2D3), normal serum level of PTH, and increased activity of serum alkaline phosphatase.

Objective and hypotheses: The aim of the study was to investigate the clinical phenotype and molecular background of HR in a family in which XLHR was suspected.

Method: Two siblings, an older brother aged 14 years and 1 month and his younger sister aged 12 years and 10/12 months, were diagnosed with HR due to clinical and biochemical picture. All exons of PHEX gene were amplified using PCR and directly sequenced.

Results: The dominant clinical sign in both patients was bowing of legs (genu varum in a boy and genu valgum in a girl). Short stature, predominantly affecting the brother, and lumbar hyperlordosis were also observed. Short stature and genu varum were also seen in affected mother. The difference in height was probably due to the time of treatment introduction, as it was initiated in the girl in the infantile period before the clinical signs appeared. In both patients a novel c.1483-1G>A mutation in intron 13 was identified. This mutation was also present in the affected mother leading to changes in the transcription of the RNA.

Conclusion: The early diagnosis of XLHR is very important for proper treatment and to prevent severe bone deformities and improve final height. The molecular analysis of PHEX gene is very important for the confirmation of clinical diagnosis of HR and highlights the role of further genetic counselling in families with HR patients.

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