Hypophosphatemic rickets. Clinical cases

Abstract

Hypophosphatemic rickets (HR) is a genetically heterogeneous disease that is accompanied by hypophosphatemia, skeletal (rickets-like) disorders, growth retardation in children and adults and by damage of other organs and systems. Its incidence is 3.9 cases per 100.000 live births, and the prevalence ranges from 1.7 per 100,000 children to 4.8 per 100,000 people (children and adults).
 The study was aimed on the investigation of diagnostic features and treatment strategy of different HR subtypes and evaluation of the effectiveness of therapy. Three cases of patients with HR from two families have been described. Laboratory and instrumental investigations were used to confirm the HR. Genetic diagnosis was done using next-generation target sequencing (tNGS) (skeletal dysplasia panel).
 General clinical features of skeletal disorders (e.g. severe deformity of the lower extremities from early childhood) and growth retardation were observed in patients with HR. All patients had hypophosphatemia with normal/slightly elevated or decreased PTH levels. All patients underwent repeated surgical treatment (without appropriate laboratory and genetic testing and correction of phosphorus-calcium metabolism), which turned out to be ineffective and led to disability. In two patients from one family, genetic testing confirmed the presence of heterozygous pathogenic PHEX variant, and in one — a homozygous SLC34A3 variant. Normophosphatemia was achieved in a girl with SLC34A3 after starting therapy with the phosphorus supplements. In patients with PHEX variant, treatment with calcitriol, cholecalciferol and phosphorus supplements had little effect (P levels increased but normalization was not achieved), thus only burosumab proved to be rational therapy for such patients. Prior to any corrective surgery, a thorough laboratory and genetic examination should be performed to compensate the phosphorus-calcium metabolism. Timely initiation of pathogenetic conservative treatment can improve bone structure and final growth, as well as reduce the need for corrective surgery.