Endocrine Abstracts

Introduction: Rickets was once considered to be a disease of the Victorian Era but it has become increasingly common in recent years. The most common cause is Vitamin D deficiency; however it is important to investigate for rarer causes if Vitamin D deficiency has been excluded.

Case report: A healthy, Caucasian 3 year old girl was referred due to bowing of her femora, apparent since she started walking at 13 months. She was reported to be clumsy and tire easily. There was no history of fractures or leg pain. Her height had dropped from the 75th centile to between the 25th and 50th centiles. Investigations showed mildly low corrected calcium and phosphate, slightly raised alkaline phosphatase and a sufficient vitamin D level of 50 nmol/l. After 6 months of Vitamin D treatment, bowing had progressed and height had fallen further so further investigations were performed including: urinary calcium: creatinine ratio (normal at 0.07) and urinary phosphate: creatinine ratio (elevated at 4.36). Tubular reabsorption of phosphate was reduced in keeping with a diagnosis of hypophosphataemic rickets. This was confirmed by detection of a mutation in the PHEX gene. Skeletal survey showed lower limb abnormalities and renal ultrasound excluded nephrocalcinosis. She was treated with oral phosphate supplements and alfacalcidol, resulting in improved growth and was subsequently diagnosed with moderate sensorineural hearing loss, another feature of hypophosphataemic rickets.

Conclusion: Rickets is a disorder of the growth plate, due to inadequate supply of phosphate to growing bones. Mutations in the PHEX gene cause increased levels of fibroblast growth factor 23 (FGF23), resulting in reduced absorption of phosphate in the proximal renal tubule. It is the most common form of hereditary rickets, and usually presents before 2 years. The key feature is significant phosphaturia (calculated by TmP/GFR). Patients are at increased risk of dental complications, enthesopathy, lumbar lordosis and hearing impairment. Phosphate supplements replace renal losses and calcitriol increases phosphate absorption from the gut and reduces PTH, preventing nephrocalcinosis. A new treatment, Burosumab^® is a monoclonal IgG1 antibody that binds excess FGF23.