Vitamin D dependent rickets type 1A (VDDR-IA) is inherited in an autosomal recessive pattern and caused by mutations in CYP27B1 gene encoding enzyme 1α-hydroxylase. Deficiency of 1α-hydroxylase leads to decrease of 1,25(OH)2 vitamin D production. VDDR-IA usually manifests clinically during the 1st year of life. Clinical features of VDDR- IA include progressive growth retardation, hypotonia, rachitic skeletal deformities, hypocalcemic seizures in early infancy. Serum profiles show hypocalcemia, hypophosphatemia, secondary hyperparathyroidism and increased alkaline phosphatase activity, the serum levels of 25(OH) vitamin D are normal or raised while the levels of 1,25(OH)2D are low or undetectable. We presented here three patients with different features of VDDR- IA. One baby had of lower limb deformities and hypotonia. A 9-month-old male who presented with severe muscle weakness, failure to thrive and skeletal deformities, including multiple fractures and seizures. A 12 years old girl presented only low body weight and a muscle pain, however, bone deformities were absent. All patients had classical biochemical data of rickets: hypocalcemia, hypophosphatemia, high serum ALP and elevated PTH. Radiological findings included cupping and fraying of the radial and ulnar metaphyses. A targeted next generation sequencing approach (Ion Torrent platform) was used for sequencing of rickets candidate genes. In all patients were identified mutations in the CYP27B1 gene. DNA sequencing of the patients revealed compound heterozygosity mutations: F80LfsX79 [c.240delT] and N310D [c.928A>G]; R389H [c.1166G>A] and H240PfsX93 [c.718dupC];P74L [c.221C>T] and Q479X [c.1435C>T]. The exon 7, p.R389H mutation has previously been described and identified as disease causing, others were novel. Once alfacalcidol therapy was initiated, the patients showed significant improvement of condition and a correction of deformations. Serum calcium, phosphorous, alkaline phosphatase and parathyroid hormone returned to normal range. In conclusion, we presented patients whith different phenotype of VDDR- IA caused by 1 alpha-hydroxylase gene mutations.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology