Essam Al-Sabban

A molecular genetic analysis of childhood nephrotic syndrome in a cohort of Saudi Arabian families

Nephrotic syndrome (NS) is a renal disease characterized by heavy proteinuria, hypoalbuminemia, edema and hyperlipidemia. Its presentation within the first 3 months of life or in multiple family members suggests an underlying inherited cause. To determine the frequency of inherited NS, 62 cases (representing 49 families with NS) from Saudi Arabia were screened for mutations in NPHS1, NPHS2, LAMB2, PLCE1, CD2AP, MYO1E, WT1, PTPRO and Nei endonuclease VIII-like 1 (NEIL1). We detected likely causative mutations in 25 out of 49 families studied (51%). We found that the most common genetic cause of NS in our cohort was a homozygous mutation in the NPHS2 gene, found in 11 of the 49 families (22%). Mutations in the NPHS1 and PLCE1 genes allowed a molecular genetic diagnosis in 12% and 8% of families, respectively. We detected novel MYO1E mutations in three families (6%). No mutations were found in WT1, PTPRO or NEIL1. The pathogenicity of novel variants was analyzed by in silico tests and by genetic screening of ethnically matched control populations. This is the first report describing the molecular genetics of NS in the Arabian Peninsula.

Infantile nephrotic syndrome and congenital glaucoma.

Abstract. A case of infantile nephrotic syndrome (NS) with advanced membranoproliferative glomerulonephritis (MPGN), type I, and bilateral congenital glaucoma, is presented. The patient also had persistent thrombocytopenia and subclinical hypothyroidism. The parents were second-degree cousins and the affected infant had a sibling who was born with congenital glaucoma. His mother had an aunt and uncle on the maternal side who were born with congenital glaucoma. In addition, there was a history of infantile death in five family members of unknown causes (pedigree). To the best of our knowledge, the association of congenital glaucoma and infantile NS due to MPGN has not been reported previously.

Congenital chloride diarrhea: A single center experience with ten patients.

Congenital chloride diarrhea (CCD) is a rare autosomal recessive disorder characterized by life-long watery diarrhea with a high fecal chloride concentration. We report the clinical and laboratory data in 20 Saudi infants with CCD admitted to our center between January 1986 and December 1991. In addition to diarrhea, there was a history of maternal polyhydramnios, low birth weights, abdominal distention and failure to thrive. The mean serum and stool chloride concentrations were 71 and 146 mmol/L respectively. Diagnosis was frequently delayed in spite of the early symptoms and the unique association of diarrhea with hypochloremic alkalosis. Treatment with NaCl and KCI solutions in amounts titrated to correct their electrolyte depletion and metabolic alkalosis resulted in marked clinical improvement and growth catch-up. Congenital chloride diarrhea should be suspected in patients with watery stools starting in teh neonatal period or early infancy. The diagnosis is confirmed by the presence of a high fecal chloride concentration and the concomitant hypochloremic alkalosis.

Spectrum of renal disease in Saudi Arabia

A series of 380 kidney biopsies performed at several institutions in Saudi Arabia was reviewed and categorized as follows: primary glomerular disease, 275; renal involvement in systemic disease, 77...

PRIMARY HYPEROXALURIA TYPE I: AN UNDERESTIMATED CAUSE OF NEPHROCALCINOSIS AND CHRONIC RENAL FAILURE IN SAUDI ARABIAN CHILDREN

BACKGROUND Primary hyperoxaluria type I (PHI) is a rare metabolic disease caused by deficiency or abnormalities of the peroxisomal enzyme alanine-glyoxylate aminotransferase. In the majority of patients, the clinical expression of PHI is characterized by recurrent calcium oxalate urolithiasis, nephrocalcinosis and renal failure. PATIENTS AND METHODS Sixteen children aged 5 months to 14 years were diagnosed as PHI over a 10-year period ending in June 1997. The diagnosis was established by quantitative urinary oxalate excretion, or by a high urine oxalate/creatinine ratio on spot urines. RESULTS The majority of patients had nephrolithiasis (13/16) and/or nephrocalcinosis (12/16). Four patients already had advanced chronic renal failure at the time of diagnosis. Altogether, PHI accounted for 20% of nephrocalcinosis and 6% of end-stage renal disease. Two patients had a complete response to pyridoxine therapy, while four patients had a partial response. Eight patients underwent organ transplantation, three underwent kidney transplantation, three received combined liver/kidney transplantation for end-stage renal disease, and two received isolated preemptive liver transplantation. CONCLUSION Combined organ transplantation provided the best long-term results.

Clinical and serologic responses of Saudi children to Hemophilus influenzae type B capsular polysaccharide diphtheria toxoid conjugate vaccine.

Sixty-eight Saudi children, 17 to 19 months of age, were enrolled in a study to evaluate the safety and immunogenicity of Hemophilus influenzae type B capsular polysaccharide diphtheria toxoid (PRP-D) conjugate vaccine. Adverse reactions to the vaccine were determined through a questionnaire administered to the parents. Local and systemic reactions to the vaccine were mild and resolved within 24 to 48 hours. PRP antibody levels were measured prior to and one to two months following immunization. PRP antibody levels in the pre-immunization sera of 77% of subjects were below the level associated with immediate protection (>/=0.15 microg/ml), and 88% were below the level associated with long-term protection (>/=1 microg/ml) from Hemophilus influenzae type B (HIB) disease. After one dose of PRP-D vaccine, 100% of recipients achieved antibody levels of >/=0.15 microg/ml, and 85% achieved levels of >/=1 microg/ml. The geometric mean level of antibody after immunization (5.66 microg/ml) was significantly higher than that before immunization (0.098 microg/ml). All subjects had a twofold or greater increase in antibody level in response to the vaccine. We conclude that PRP-D is a safe and highly immunogenic vaccine in this age group of Saudi children.

Kala-Azar: Approaches to Diagnosis and Treatment

ABSTRACT Eight children (three boys and five girls) aged 2-10 years (median age 5 years) were admitted to the King Faisal Specialist Hospital and Research Centre because of fever, hepatosplenomegal...

SINGLE CENTER EXPERIENCE OF EN BLOC KIDNEY TRANSPLANTATION AND REVIEW OF LITERATURE

Cadaveric renal transplant was started at King FaisalSpecialist Hospital and Research Centre in January 1987. Asthe number of end-stage renal disease patients requiringtransplant was steadily increasing, and the shortage of organswas becoming more severe, we began using cadavericpediatric kidneys in 1989. When the age of the donor was lessthan three years, we used both kidneys together (en bloc) forone recipient.Materials and MethodsFrom 1989 to 1997, we performed seven en bloctransplants from cadaveric donors aged between seven monthsand three years. Five of the seven patients were adults, and twowere pediatric recipients. It was the second transplant in thefirst three recipients. The donor aorta and vena cava weresewn at their proximal ends. The distal end of the aorta wasanastomosed to the external iliac artery and the vena cava tothe external iliac vein. The ureters were sutured to make asingle opening and anastomosed to the bladder as extravesicalureteroneocystostomy (Figure 1).All the patients except Case numbers 3 and 7 receivedquadruple sequential therapy ALG or ATG, prednisone,cyclosporin or FK506 and Imuran or M ycophenolate Mofetil(MMF). The monoclonal antibody OKT3 was used for steroid-resistant rejection. FK506 was used as first-line treatment, oras rescue therapy in resistant rejection. Of late, MMF is beingused as an initial immunosuppression.ResultsCase number 1 received an en bloc kidney transplant in1989, and was given anti-thymocyte globulin (ATG) asinduction. The patient developed two episodes of biopsy-proven rejection at 21 days and at two months, and was givenOKT3 for 10 days. The kidneys never functioned andtransplant nephrectomy was performed on the 68th day. The