Bone and Mineral Metabolism

MON-820 - A Late Diagnosis of X-Linked Hypophosphatemic Rickets in A 15-Year-Old Male: The Importance of the Genetic Evaluation for Short Stature

Monday, June 15, 2026

9:00 AM - 2:00 PM CT

Location: ENDOExpo; Poster Floor

Abstract Poster Presenter(s)

VT

Vanessa Torrice, MD

Fellow
Icahn School of Medicine at Mount Sinai
New York, New York, United States

Co-Author(s)

MV

Marisa Vomvos, MS, CGC

Icahn School of Medicine at Mount Sinai
New York, New York, United States

Senior Author/Primary Investigator(s)

CR

Christopher Joseph Romero, MD

Associate Professor
Icahn School of Medicine at Mount Sinai
New York, United States

Background:
X-Linked Hypophosphatemic (XLH) Rickets is a rare genetic disorder that leads to hypophosphatemia and poor bone formation. Patients present with bowing of the lower extremities, short stature, and joint/muscle pain. In mild forms, patients may present with short stature. Mutations of the PHEX gene lead to a rise in FGF23, which cause the kidneys to excrete excess phosphorous. It is transmitted as an X-linked dominant trait with complete penetrance, but variable expressivity.

Case Report:
We present a 15-yr old male with growth hormone (GH) deficiency (peak stimulated GH of 4.1 ng/dl, height -2.57 SD) treated with GH therapy since age of 9 years. Additional short stature workup was normal including calcium and vitamin D levels. His growth response was suboptimal and parents were reluctant to obtain a genetic evaluation. Follow up studies showed normal calcium, phosphorus and mildly elevated PTH 62 (9-59 pg/ml).
At age 12 years a hip x-ray for hip pain was reported normal with normal bone mineralization. At 15 years, he reported knee pain; orthopedics diagnosed a knee varus deformity with bilateral proximal tibial and distal femoral bowing; also widening of the physis of the distal femurs consistent with rickets. Repeat labs showed a low phosphorous level 2.6 mg/dl, calcium 9.7 mg/dl, magnesium 2.1 mg/dl, vitamin D 25, OH 43, PTH 111 pg/ml and alkaline phosphatase 557 U/L. A calculated fractional excretion of phosphate was elevated.
Genetics with an Invitae Skeletal Disorders Panel resulted with multiple variants of uncertain significance, most notably a hemizygous variant of uncertain significance in PHEX (c.732+3A>T). This change falls within a consensus splice site, and algorithms developed to predict the effect of sequence changes on RNA splicing suggests this variant may cause aberrant splicing. It is not present in population databases (gnomAD) and has been observed in individuals with X-linked hypophosphatemia.
The patient was treated with oral phosphorous replacement with improvement of phosphorous levels. The patient also underwent epiphysiodesis with bilateral tibial lateral Epifix Plates to prevent further leg bowing. There is now discussion about treatment with burosumab.
CONCLUSION
In summary, we present a rare case of XLH in a child initially treated for GH deficiency for several years but found to have an inadequate response to GH therapy. Early in treatment this patient had normal metabolic panels including normal calcium, vitamin D and phosphorous level, but these were not checked again until recently. This case highlights the importance of the thorough exploration of etiologies for short stature despite previously documented pathology, especially when GH response to treatment is poor. This case stresses the role of genetic testing for skeletal dysplasia in children with significant short stature, regardless of any known pathology if growth clinically remains poor.

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