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KEYWORDS Nephrogenic Diabetes Insipitus. X-linked Recessive Disorder. AVPR2. mutation ABSTRACT Congenital nephrogenic diabetes insipidus (NDI) is a rare X-linked recessive disorder associated with germline mutations of the arginine vasopressin (AVP) receptor type 2 (AVPR2) gene. The researchers describe a novel mutation in the AVPR2 gene in a three-generational Turkish family with NDI. In the present report, a 22-year-old man is reported with polyuria and bilateral non-obstructive hydronephrosis. He was diagnosed with partial NDI based on the clinical phenotype, the water deprivation test and the inadequate response to 1-desamino-8-Darginine vasopressin (DDAVP) administration. All family members who were suspected to have diabetes insipidus and/or related symptoms were studied. Sequencing analysis of the AVPR2 gene revealed the novel missense mutation c.392 T>C; p. Leu 131 Pro:L131P (AVPR2 gene (coding seq # NM_000054.4;prot seq # NP_000045.1). In conclusion, the proband carries a novel AVPR2 missense mutation inherited from his carrier mother.

A 14-month-old boy with Menkes’ kinky hair syndrome (MS) associated with deafness and inferior cerebellar vermian hypoplasia was admitted with convulsions and urinary infection at Karadeniz Technical University, Trabzon, Turkey.

The results of carrier and prenatal diagnosis for Lesch-Nyhan syndrome by carrier testing of 83 women and prenatal analysis of 26 pregnancies are reported from the Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX.

Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy. Background Fabry disease, a lysosomal storage disease caused by deficient lysosomal α-galactosidase A activity, is characterized by globotriaosylceramide (GL-3) accumulation in multiple cell types, particularly the vasculature, leading to end organ failure. Accumulation in the kidney is responsible for progressive decline in renal function in male patients with the classical phenotype, resulting in renal failure in their third to fifth decades of life. With the advent of recombinant protein synthesis technology, enzyme replacement therapy has become a viable alternative to dialysis or renal transplantation, previously the only available treatment options for end-stage renal disease. Methods The pre- and post-treatment renal biopsies were analyzed from fifty-eight Fabry patients enrolled in a Phase 3 double-blind, randomized, placebo-controlled trial followed by a six-month open label extension study of the recombinant human enzyme, α-galactosidase A (r-hαGalA), administered IV at 1mg/kg biweekly. The purpose of this investigation was to detail the pathologic changes in glycosphingolipid distribution and the pattern of post-treatment clearance in the kidney. Results Baseline evaluations revealed GL-3 accumulations in nearly all renal cell types including vascular endothelial cells, vascular smooth muscle cells, mesangial cells and interstitial cells, with particularly dense accumulations in podocytes and distal tubular epithelial cells. After 11 months of r-hαGalA treatment there was complete clearance of glycolipid from the endothelium of all vasculature as well as from the mesangial cells of the glomerulus and interstitial cells of the cortex. Moderate clearance was noted from the smooth muscle cells of arterioles and small arteries. Podocytes and distal tubular epithelium also demonstrated evidence for decreased GL-3, although this clearance was more limited than that observed in other cell types. No evidence of immune complex disease was found by immunofluorescence despite circulating anti-r-hαGalA IgG antibodies. Conclusions These findings indicate a striking reversal of renal glycosphingolipid accumulation in the vasculature and in other renal cell types, and suggest that long-term treatment with r-hαGalA may halt the progression of pathology and prevent renal failure in patients with Fabry disease.