Abstract 172

Abstract

Introduction: Dent’s disease is a rare X-linked renal tubulopathy characterized by low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and progressive renal failure. Common features are rickets or osteomalacia, growth retardation, and short stature. Short staturein children suffering from this diseasecould be multifactorial, including rickets, GH resistance, reduced GH secretion rate or functional IGF deficiency and increased IGFBP. To the best of our knowledge, this is only the fourth report on the use of growth hormone therapy in a child with poor growth associated with Dent’s disease. We report two siblings with Dent’s disease and growth failure who responded to growth hormone (GH) treatment. Summary: Initially the elder sibling presented at the age of five yearsto pediatrics with proteinuria, calciuria, phosphaturia and growth failure and was treated with calcium, vitamin D and multivitamin supplementation and ACE inhibitor. During evaluation foretiology of renal wasting, genotyping revealed ahemizygous two base pair duplication in exon 6 of the CLCNS gene resulting in frame-shiftmutation. Laterthe younger sibling presented with similar features and hence he was also subjected to genotyping which revealed same mutation along with parents being carriers. Both were referred to us for short stature at a chronological age of 11 years (younger) and 15 years (older). Evaluation revealed GH deficiency (IGF 49.21 ng/ml range 37-459) in the younger brother but elder brother had normal GH-IGF axis along with features of Rickets and nephrocalcinosis in both brothers. Bone-age was delayed in both, 4.5 years and 11 years respectively. Literature search revealed three different cases of short stature where GH therapy had been tried with success. Hence GH therapy was started at the dose of 0.18 mcg/kg/week in both along with vitamin D, potassium, phosphorous supplements and thiazide diuretic. After 1 year of GH treatment, height increased from 113 cm (−4.1 S.D.) to 121.5 cm (− 3.5 S.D.) in younger one and 139 cm (-3.5 SD) to 148 cm (-2.7 SD) in the elder brother. IGF-1 levels increased in the younger one from 49.2 ng/ml (37-459) to 191 ng/ml. Bone age also increased from 4.5 years to 6.5 years in the younger one and from 11 years to 13 years in the elder sibling. Our preliminary findings showed beneficial effects of GH treatment on growth velocity of around 8 cm in younger sibling and 9 cm in elder sibling after one year. GH treatment should be considered in children with Dent’s disease and short stature since positive effects on linear growth can be obtained.