Rare and heterogeneous manifestations of leucocyte adhesion deficiency type 1: report of two cases with diagnostic dilemmas and novel ITGB2 mutation.

BACKGROUND: Primary immunodeficiency disorders (PID) are rare disorders with heterogeneous manifestations, overlapping with other diseases such as autoimmunity, malignancy, and infections. This makes the diagnosis very challenging and delays management. Leucocyte adhesion defects (LAD) are a group of PIDs in which patients lack adhesion molecules on leukocytes needed for their emigration through blood vessels to the site of infection. Patients with LAD can present with diverse clinical features including severe and life-threatening infections, early in life, and the absence of pus formation around infection or inflammation. There is often delayed umbilical cord separation, omphalitis, late wound healing, and a high white blood cell count. If not recognized and managed early, can lead to life-threatening complications and death. CASE PRESENTATION: LAD 1 is characterized by homozygous pathogenic variants in the integrin subunit beta 2 (ITGB2) gene. We report two cases of LAD1 with unusual presentations (post-circumcision excessive bleeding and chronic inflammation of the right eye) which were confirmed by flow cytometric analysis and genetic testing. We found two disease-causing ITGB2 pathogenic variants in both cases. CONCLUSIONS: These cases highlight the importance of a multidisciplinary approach to recognizing clues in patients with uncommon manifestations of a rare disease. This approach initiates a proper diagnostic workup of primary immunodeficiency disorder leading to a better understanding of the disease, and appropriate patient counseling, and helps clinicians to be better equipped to deal with complications.

Laparoscopic Donor Nephrectomy: Early Experience at a Single Center in Pakistan.

OBJECTIVES: Laparoscopic donor nephrectomy has become the criterion standard for kidney retrieval from living donors. There is no information on the experience and outcomes of laparoscopic donor nephrectomy in Pakistan. The objective of the study was to identify benefits and harms of using laparoscopic compared with open nephrectomy techniques for renal allograft retrieval. MATERIALS AND METHODS: In this a retrospective study, patient files from May 2014 to September 2015 were analyzed. Patients were divided into 2 groups: those with open donor nephrectomy and those with laparoscopic donor nephrectomy. Donor case files and operative notes were analyzed for age, sex, laterality, body mass index, warm ischemia time, perioperative and postoperative complications, surgery time, and length of hospital stay. Finally, serum creatinine patterns of both donors and recipients were analyzed. Data were analyzed using SPSS version 10 (SPSS: An IBM Company, IBM Corporation, Armonk, NY, USA). RESULTS: Of 388 total donors, 190 (49%) had open donor nephrectomy and 198 (51%) had laparoscopic donor nephrectomy. For both groups, most donors were older than 25 years with male preponderance. Left-to-right kidney donation ratio was markedly higher in the laparoscopic group than in the open donor nephrectomy group, with 6 cases of double renal artery also included in this study. There were no significant differences in surgery times between the 2 groups, whereas the laparoscopic donor nephrectomy group had shorter hospital stay. Analgesic requirements were markedly shorter in the laparoscopic donor nephrectomy group. The 1-year graft function was not significantly different between the 2 groups. CONCLUSIONS: The results for laparoscopic donor nephrectomy were comparable to those for open donor nephrectomy, and its acceptability was high. Laparoscopic donor nephrectomy should be the preferred approach for procuring the kidney graft.

Regulated compensated donation in Pakistan and Iran.

PURPOSE OF REVIEW: Paid living unrelated kidney donor transplantation has flourished in Pakistan and Iran. This review discusses the dynamics and consequences of organ trade in Pakistan and of a regulated paid donor model in Iran on transplant activities in these countries. RECENT FINDINGS: In 2007, over 2500 renal transplants were performed in Pakistan, where more than 70% were from socioeconomic disadvantaged kidney vendors. More than half of recipients were foreigners who paid US$20,000-30,000. Recipients of vendor kidneys had poor outcome and high infectious complications. Regulated paid donor kidney transplant in Iran number around 1500 per year and constitute 70% of the total transplants. Graft survival rates are similar to those for living related donors. The donors are paid US$1200 and additional monies are negotiated between the recipient-donor pair. This model claims to have abolished waiting lists, although many poor patients wait for deceased donors. In both countries, recipients are relatively rich and vendors are the poor of the society who sell kidneys for quick money or to repay debts. SUMMARY: Paid donation, regulated or commercial, leads to coercion and exploitation of the poor and benefits the rich. This situation has forestalled deceased donor program and hence other solid-organ transplants. The way forward is to promote deceased donors by making transplant available to all who need it.

Celiac disease in children with persistent diarrhea and failure to thrive.

OBJECTIVE: To determine the frequency of celiac disease (CD) in children with failure to thrive (FTT) and/ or persistent diarrhea (PD) not responding to conventional therapy. DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Gastroenterology Unit of Sindh Institute of Urology and Transplantation (SIUT), from January 2002 to January 2004. PATIENTS AND METHODS: Forty nine children and adolescents with PD (defined as diarrhea greater than 14 days duration) and / or FTT (based on anthropometrical indicators, i.e. weight for length below the 5th centile) were included in the study. Demographic data, weaning practices, breast feeding and family history of CD were documented. Laboratory workup included tissue transglutaminase antibody IgA (tTGA), IgA and IgG antigliadin antibodies (IgA AGA and IgG AGA), HLA typing, upper gastrointestinal endoscopy (EGD) with distal duodenal biopsy (where allowed by parents) and anthropometric data. CD diagnosis was in accordance with the "Guidelines for the diagnosis of and treatment of CD for children" by NASPGHAN. Mann-Whitney U-test, Chi-square test and Fisher's exact test were used for analysis as applicable. RESULTS: Forty nine patients (25 [51%] males) with FTT and or PD were included. The mean (+/-SD) age, height, weight and BMI were: 10.1+/-6.2 years (range, 1-20 years), 107.0 +/- 31.7 cm (45-180 cm), 19.04 +/- 12.5 kg (3-68 kg) and 16.12+/-12.58 kg/cm2 respectively. FTT was present in 30 (61%) patients. Thirty four (69%) children had a history of PD, 38 (77%) had a significant history of weight loss and 32 (65%) children had short stature. Majority of the children (88%) were breast fed. Weaning was started at 6 months of age in 40% and included mixed diet according to age. Protuberant abdomen was present in 26 (53%). Elevated tTGA was significantly (p < 0.001) more frequent in patients with CD. HLA-DQ2 and DQ8 haplotypes were positive in 18 (60%) of these patients. Thirty (61%) patients were positive for CD based on Marsh criteria. CD diagnosis was supported by positive tTGA and/ or AGA tests. Majority i.e. 28/30 patients had Marsh stage 3 disease, while 22/30 patients with CD also had PD. Four CD patients were found to suffer from protein calorie malnutrition (PCM). CONCLUSION: Children who fail to thrive with or without PD may have CD. A positive tTGA test in these children is a useful aid in making a CD diagnosis. Majority of CD positive children were found to carry HLA DQ2 or DQ8 genes. Thus, HLA typing could be used to determine genetic disposition to CD. Majority of FTT had Marsh stage 3 changes on histopathology.

Crescentic glomerulonephritis associated with bacterial endocarditis--antibiotics alone may be sufficient. A case report.

Crescentic glomerulonephritis complicating the course of bacterial endocarditis carries a poor prognosis. Ideal treatment strategy is not clearly defined. In addition to antibiotic treatment, plasmapheresis and steroids have been used with variable results. Here we report a case of 40-year old female who was referred because of generalized body swelling and decrease urine output associated with low grade fever on and off for two to three months. She was diagnosed to have acute renal failure secondary to tricuspid valve endocarditis. Staph aureus was isolated from blood culture and renal biopsy showed crescentic glomerulonephritis. She received dialysis support and antibiotics and had complete recovery of renal function 6 weeks after initiation of therapy. Eradication of infection with antibiotics treatment may be sufficient for resolution of crescentic glomerulonephritis associated with infective endocarditis in some cases.

Biliary atresia with situs inversus: an experience shared.

Biliary Atresia (BA) is a well-known entity and can present with multiple congenital anomalies. BA is one of the most common conditions in which pediatric liver transplant is performed. Identification of Biliary atresia with situs inversus (SI) has not been documented in Pakistan. We report two such cases. First was an eighty-day-old baby boy, icteric from day of birth. On further evaluation had dextrocardia, SI, gross hydronephrosis (HN) of left kidney and stasis at pelvi ureteric junction (PUJ). Liver biopsy showed biliary cirrhosis secondary to extra hepatic biliary atresia (EHBA). The second baby presented at two months of age. Ultrasound abdomen and hepatobiliary scintigraphy confirmed liver in left hypochondrium (SI) and findings suggestive of BA. Echocardiography confirmed SI with mesocardia. In this paper we have described the association of BA with SI in two patients presenting at the pediatric Gastroenterology, hepatology and nutrition unit.

Middle East Society for Organ Transplantation (MESOT) Transplant Registry.

During the seventies, sporadic renal transplants were performed in few MESOT-region countries, mainly Turkey, Iran, Egypt, and Lebanon. Since the introduction of cyclosporine in the early eighties, transplantation has become the preferred therapeutic modality for end-stage renal failure. In 1986, the Islamic theologians (Al Aloma) issued what became known as the Amman declaration, in which they accepted brain death and retrieval and transplantation of organs from living and cadaveric donors. Based on this and similar declarations, all Middle Eastern countries except Egypt passed laws that allow cadaveric transplantation and regulate live donations. Iran, Turkey, Saudi Arabia, Kuwait, Tunisia, Jordan, and Lebanon all have current active cadaveric programs and perform liver, heart, pancreas, and lung transplants. More than 5088 renal transplants/year are performed in the region with Iran leading with 1600. The cumulative number of renal transplant patients is now nearly 60,000. With a 2003 population of 600,682,175, the rate/million for renal transplantation in the MESOT region is a mere 9/million. Rates of renal transplantation range from 31/million in some countries to 0 in others. The major obstacle in establishing an accurate number of transplants is "tourist transplantation," in which the same transplanted patients are registered in different countries. Although cadaveric programs have been active for more than 10 years, live-related and nonrelated transplants account for nearly 85% of the total transplants. The data presented were collected from MESOT representatives in the region and from publications. For proper compilation of the registry, a format is being proposed that will be presented at the Congress for review and adaptation. Even with the limited resources in the region, immunosuppressive drugs for induction and maintenance therapy are available and are used. Costs for transplantation and immunosuppressive therapy are either totally or heavily supported by governmental agencies.