The recent discovery of mutations in the gene encoding diacylglycerol kinase (DGKE) identified a novel pathophysiologic mechanism leading to HUS and/or MPGN. We report ten new patients from eight unrelated kindreds with DGKE nephropathy. We combined these cases with all previously published cases to characterize the phenotypic spectrum and outcomes of this new disease entity. Most patients presented with HUS accompanied by proteinuria, whereas a subset of patients exhibited clinical and histologic patterns of MPGN without TMA. We also report the first two patients with clinical and histologic HUS/MPGN overlap. DGKE-HUS typically manifested in the first year of life but was not exclusively limited to infancy, and viral triggers frequently preceded HUS episodes. We observed signs of complement activation in some patients with DGKE-HUS, but the role of complement activation remains unclear. Most patients developed a slowly progressive proteinuric nephropathy: 80% of patients did not have ESRD within 10 years of diagnosis. Many patients experienced HUS remission without specific treatment, and a few patients experienced HUS recurrence despite complete suppression of the complement pathway. Five patients received renal allografts, with no post-transplant recurrence reported. In conclusion, we did not observe a clear genotype-phenotype correlation in patients with DGKE nephropathy, suggesting additional factors mediating phenotypic heterogeneity. Furthermore, the benefits of anti-complement therapy are questionable but renal transplant may be a feasible option in the treatment of patients with this condition.

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy with severe clinical manifestation, frequent recurrence, and poor long-term prognosis. It is usually caused by abnormalities in complement regulation. We report 2 cases of children affected by a catastrophic extrarenal complication. A 4-year-old Indian girl developed gangrene of the finger tips 2 days after initial presentation of aHUS. Factor H autoantibodies were identified. Renal function continued to decline despite daily plasma exchanges, and she was started on peritoneal dialysis 5 days after admission. The distal tips of the left hand remained gangrenous with a line of demarcation. Three weeks later, she did not return for follow-up and died at home because of dialysis-related complications. An Arabic girl developed end-stage renal disease due to aHUS in the fourth month after birth. A de novo activating C3 mutation was found. At age 9 months, she suddenly developed ischemic changes in fingers of both hands and several toes. The lesions progressed, and several finger tips became gangrenous despite intense plasma exchange therapy. The decision was made to administer complement blocking therapy with the C5 antibody eculizumab. All nonnecrotic digits rapidly regained perfusion. The 3 already gangrenous fingers healed with loss of the end phalanges. During maintenance, eculizumab aHUS activity subsided completely and some late recovery of renal function was observed. aHUS may present by thrombotic macroangiopathy of small peripheral arteries. Eculizumab appears effective in preserving tissue viability if administered before gangrene occurs and should be considered as first-line rescue therapy in such cases.

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Background: Ileal perforation is a very critical condition. Objectives: The purpose of the present study was to see the post-operative mortality after ileal perforation. Methodology: This prospective cohort study was conducted in the Department of Surgery at Dhaka Medical College Hospital, Dhaka, Bangladesh from September 2000 to December 2002 for period of 2 years and 3 months. All the patients presented with ileal perforation at any age with both sexes were included in this study. Patients were selected consecutively and the patients who showed ileal perforation at laparotomy were included in this study. Preoperative diagnosis was based on detailed history, complete physical examinations supported by plain x-ray abdomen in erect posture including both domes of diaphragm. After immediate resuscitation surgical treatment was undertaken as soon as possible following admission in all cases. The patients were followed up and the mortality profiles were recorded after surgical intervention. Result: Out of 53 patients having postoperative complications 38 patients were survived and 15 patients were expired. So total survivors were 85% and non-survivors 15%. In this study most of the mortality (12%) was attributed to septicemia and mode of death was multiple organ failure. Respiratory complications caused 2% mortality one patient died of ARDS and another elderly patient with preexisting bronchial asthma developed respiratory failure and was unresponsive to treatment. One death was related to faecal fistula followed by severe fluid, electrolyte and acid-base imbalance with peritonitis and gross sepsis. Conclusion: In conclusion, the mortality is significantly high due to septicemia, ARDS and faecal fistula.