Endocrine Abstracts

We report a Pakistani family of three adults and five children affected with same disorder. An 8-year-old boy referred to us for the management of osteogenesis imperfecta according to mother he was not gaining height, increasing head size, and bowing of legs since the age of 2 years. He had dental caries and brittle teeth. Two of his maternal uncles and one maternal aunt were suffering from the same disease; their children also showed similar complaints. A paternal uncle and aunt were also treated as osteogenesis imperfecta. On examination, he was noticeably short for his age and had signs of rickets ilike frontal bossing, wrist widening, chest deformity, rachitic rosary, and genu valgum. So on index of suspicion of rickets further workup was done. His investigations revealed calcium, magnesium, 25(OH)-Vitamin D along with 1,25(OH)2-Vitamin D were normal, PTH was high, his phosphorus level was low along with raised alkaline phosphatase activity. His fractional excretion of urinary phosphorus was high along with raised TRP and TmP/GFR, which were consistent with renal phosphate wasting. His skeletal survey was suggestive of Rickets. Meanwhile, the family was convinced to have a genetic work up. Due to affordability issue, the paternal uncle’s genetic work up was sent first. The initial genetic panel for osteogenesis imperfecta was negative. Later on, a panel for rickets was requested which was positive for PHEX gene.Genetic workup of index case revealed a hemizygous pathogenic mutation in Exon 17 of PHEX gene and the pathogenic variant identified was c.1735G>A (p.Gly579Arg), which is associated with X-linked hypophosphatemia. His mother also had the same pathogenic variant on genetic analysis. Other affected family members were found to be positive for the same pathogenic variant. The conventional therapy with phosphorus and calcitriol supplement was started and the patient showed significant improvement. Novel therapy Burosumab is not available in Pakistan\. This case highlights the importance of considering XLH in patients with predominant lower limb involvement along with dental problems. It also emphasizes the significance of thorough history, examination, proper investigation, genetic work up and appropriate management strategies to optimize outcome.