Report of two unrelated patients with hereditary vitamin D resistant rickets due to the same novel mutation in the vitamin D receptor.

BACKGROUND/AIMS: Two unrelated patients found to have hereditary vitamin D resistant rickets (HVDRR) were admitted to our hospital. METHODS: This article describes the diagnosis, management and molecular basis for their disease. RESULTS: Both patients had severe growth and motor developmental retardation, rickets with chest deformities and pulmonary abnormalities, but no alopecia. Both had hypocalcemia, secondary hyperparathyroidism and susceptibility to pulmonary infections. In both cases, good response with normalization of abnormal biochemistries and healing of rickets was achieved with IV calcium infusion. Subsequently, improvement was maintained with oral calcium. Both children harbored the same unique missense mutation in the vitamin D receptor (VDR) gene that substituted arginine with histidine at amino acid 274 (R274H) in the VDR ligand-binding domain (LBD). R274 is a contact point for the 1alpha-hydroxyl group of 1,25(OH)2D3, the active ligand for the VDR. Functional analyses of the R274H mutation revealed a 100-fold decrease in activity compared to wild-type VDR. CONCLUSION: We describe a novel missense mutation at R274H in the VDR gene that resulted in the HVDRR syndrome in two unrelated children. Vigorous treatment using IV calcium to normalize their hypocalcemia achieved dramatic improvement in these complex and severely ill patients.

Incidence trends of childhood type 1 diabetes in eastern Saudi Arabia.

OBJECTIVE: To assess the epidemiology and incidence rate of type 1 diabetes in children <15 years of age in a subpopulation in the eastern province of the Kingdom of Saudi Arabia (KSA). METHODS: This is a subpopulation-based observational incidence study. Admission dates, diagnosis, age, and gender were collected for all Saudi children <15 years of age with new onset type 1 diabetes that received medical care at the Saudi Aramco Medical Services Organization, Dhahran Health Center, Dhahran, KSA during the period 1990-2007. The case ascertainment rate was estimated to be 100%. RESULTS: There were 438 patients diagnosed during the study period. The average incidence rate was 27.52/100,000/year (95% CI: 26.72-28.32), increasing from 18.05/100,000/year in the first 9 years of the study period to 36.99/100,000/year in the last 9 years. Twenty-one percent of patients were <5 years of age, with no significant difference in the rate of increase in the incidence rate of this age group compared to the older age groups. Of the total patients, 55% were females, and 40% presented with diabetic ketoacidosis. CONCLUSION: The incidence rate of childhood type 1 diabetes increased alarmingly over the past 18 years in our study population. A Kingdom-wide diabetes registry is essential to study the epidemiology of this disease in the whole country.