Combined saposin deficiency: A rare occurrence.

Combined saposin deficiency (OMIM #611721), an exceedingly rare lysosomal storage disorder, is caused by a mutation in the gene PSAP. This gene encodes a protein, prosaposin, that cleaves into four constituent proteins, each of which has a role as a cofactor for the enzymes whose deficiency results in Krabbe disease, metachromatic leukodystrophy, Gaucher disease, and Farber disease, respectively. Intact prosaposin itself is essential for neuronal survival. The typical manifestation of combined saposin deficiency is of severe neurological features in the neonatal period, hepatosplenomegaly, thrombocytopenia, and early death. We report, to the best of our knowledge, the first Indian case with these clinical manifestations and confirmation by genetic and enzymatic testing.

Posttransplant Lymphoproliferative Disorder: Experience from a Pediatric Nephrology Unit in North India.

Posttransplant lymphoproliferative disorder (PTLD) is reported in 1%-3% among pediatric renal allograft recipients. We report the experience of PTLD among pediatric renal allograft recipients at a pediatric nephrology center in North India. Four cases of PTLD were identified from among records of 95 pediatric renal allograft recipients over a period of 21 years. Constitutional and localizing symptoms were present in three patients each. The diagnosis was suggested on positron emission tomography in three patients and confirmed by histopathology in all. Sites affected included tonsils, cervical lymph nodes, duodenum, and para-aortic lymph nodes in one patient each. The lymphocytic infiltrate was polymorphic in three patients and monomorphic in one. Immunostaining suggested B-cell origin in all patients. There was evidence of Epstein-Barr virus infection in only one patient. The patients were successfully managed with reduction of immunosuppression (in all), rituximab (in 3), and excision of affected tissue (in 1). Over a follow-up period of 30-88 months, there were no episodes of disease recurrence or allograft rejection, and renal function was preserved.

Targeted exome sequencing in anti-factor H antibody negative HUS reveals multiple variations.

BACKGROUND: Genetic susceptibility to atypical hemolytic uremic syndrome (aHUS) may lie within genes regulating or activating the alternate complement and related pathways converging on endothelial cell activation. METHODS: We tested 32 Indian patients of aHUS negative for antibodies to complement factor H for genetic variations in a panel of 15 genes, i.e., CFH, CFHR1-5, CFI, CFB, C3, CD46, MASP2, DGKE, ADAMTS13, THBD and PLG using next-generation DNA sequencing and for copy number variation in CFHR1-3. RESULTS: Despite absence of a public database of exome variations in the Indian population and limited functional studies, we could establish a genetic diagnosis in 6 (18.8%) patients using a stringent scheme of prioritization. One patient carried a likely pathogenic variation. The number of patients carrying possibly pathogenic variation was as follows: 1 variation: 5 patients, 2 variations: 9 patients, 3 variations: 5 patients, 4 variations: 9 patients, 5 variations: 2 patients and 6 variations: 2 patients. Homozygous deletion of CFHR1-3 was present in five patients; none of these carried a diagnostic genetic variation. Patients with or without diagnostic variation did not differ significantly in terms of enrichment of genetic variations that were rare/novel or predicted deleterious, or for possible environmental triggers. CONCLUSION: We conclude that genetic testing for multiple genes in patients with aHUS negative for anti-FH antibodies reveals multiple candidate variations that require prioritization. Population data on variation frequency of the Indian population and supportive functional studies are likely to improve diagnostic yield.

Experience with Continuous Renal Replacement Therapy.

Information on provision of continuous renal replacement therapy (CRRT) in critically ill children from developing countries is limited. The authors describe their experience in 17 children with hypotension and acute kidney injury (AKI) with fluid overload or electrolyte imbalance managed by 20 sessions of CRRT. The median (range) age and weight were 6 y (0.75-18) and 20 kg (6.2-42), respectively. All patients were receiving inotropic agents; nine had fluid overload (19 %, range 11-34.1 %) and ten had severe AKI. Median clearance and filter-life were 2171.4 ml/1.73 m(2)/h (1730.6-4405.8) and 69.7 h (2.8-98.3), respectively. Complications were catheter flow related (n = 1), filter clotting (n = 3), hemorrhage (n = 3), hypokalemia (n = 16) and hypophosphatemia (n = 11). Eight patients (47.1 %) survived; the median PRISM III score of survivors was significantly lower than non survivors (10.5 vs.17.0; P 0.02). Renal function recovered in the survivors emphasizing the role of this modality in managing critically ill patients.