Endocrine Abstracts

JOINT292630

Introduction: X-linked hypophosphatemic rickets (XLH; OMIM 307800) results from renal phosphate wasting, impaired intestinal calcium and phosphate absorption, and abnormal vitamin D metabolism due to elevated fibroblast growth factor 23 (FGF23). Patients present with early-onset rickets, skeletal deformities, short stature, bone pain, craniosynostosis, and dental anomalies. XLH is the most common inherited rickets form, with a prevalence of 1 in 20, 000 to 60, 000 individuals. It is caused by dominant inactivating variants in the PHEX gene on XP22. 11. This report discusses two siblings initially diagnosed with achondroplasia but later confirmed to have XLH.

Patients: I. B., a 60-year-old female, had a history of achondroplasia and osteoporosis but had not sought medical care for years. She presented with widespread leg pain and walked with two crutches. Her height was 110 cm, weight 33 kg, and she exhibited genu varum deformity. She had multiple past fractures but was not on regular medication. N. B., a 52-year-old female, had achondroplasia, osteoporosis, bilateral hearing loss, and primary hyperparathyroidism (surgically treated 24 years ago). She sought evaluation due to body pain and walked with one crutch. Her height was 115 cm, weight 35 kg, and she also exhibited genu varum. She had a history of leg fractures and was not taking medication. Family history revealed their father’s height was 110 cm, their mother’s 140 cm, with no consanguinity. The family had six children (three females, three males); all females had short stature, while males were at least 160 cm tall. Both sisters were misdiagnosed with achondroplasia 30 years ago without genetic testing. Recent genetic analysis identified a heterozygous c. 207_212del (p. K69_V70del) variant in PHEX (NM_000444. 6), classified as a ‘Variant of Uncertain Significance’ (VUS) per American College of Medical Genetics (ACMG)guidelines. Genetic counseling and segregation analysis were recommended.

Conclusion: These cases highlight diagnostic challenges in distinguishing XLH from achondroplasia, stressing the importance of genetic evaluation for accurate diagnosis. Misdiagnosis can delay appropriate management, underscoring the need for increased awareness and thorough genetic assessments in such cases.