Genetic mutation in Egyptian children with steroid-resistant nephrotic syndrome.

BACKGROUND/PURPOSE: Nephrotic syndrome is the commonest etiology of proteinuria in children. Steroid-resistant nephrotic syndrome (SRNS) is defined by resistance to standard steroid therapy, and it continues to be one of the most intractable etiologies of renal failure. Molecular studies discovered specialized molecules in podocytes that play a role in proteinuria. Mutations in NPHS2 that encodes for podocin constitute a frequent cause of SRNS worldwide. This study aimed to screen for podocin mutations in SRNS Egyptian children and their parents. METHODS: Our study included patients from 10 unrelated Egyptian families diagnosed with SRNS. Mutational analysis of the NPHS2 gene was performed by polymerase chain reaction amplification of the whole coding region of the gene and direct sequencing. RESULTS: Positive consanguinity was detected in five cases, and four of them had a positive family history of SRNS in a family member. Mutational analysis of NPHS2 revealed pathogenic mutations in four cases (40%) including a novel missense in one patient (c.1A>T; p.M1L). CONCLUSION: Our study concludes that mutations of NPHS2 gene are common among Egyptian children with SRNS. We support a model where ethnicity plays an important role in specific NPHS2 mutations, since a novel mutation was found in one patient in this study. Future study on a large number of Egyptian patients with SRNS is warranted to identify the actual genetic contribution of this gene in the development of SRNS in our population, which might help in patients' prognosis and management.

Could Congenital Insensitivity to Pain with Anhidrosis Be Misdiagnosed as Papillon-Lefèvre Syndrome?

Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder characterized by early loss of teeth with hyperkeratosis of the palms and soles. Congenital insensitivity to pain with anhidrosis (CIPA) is a disorder of decreased pain sensation, decreased sweating, recurrent infections, and fever. Here, we report a 5-year-old girl born to consanguineous parents with a family history of a similarly affected sibling. The girl presented with early loss of teeth and palmoplantar hyperkeratosis, hence, provisionally diagnosed as PLS. Further clinical examination and detailed history taking shifted the diagnosis to CIPA. CIPA could be misdiagnosed as PLS. Congenital insensitivity to pain with anhidrosis, although rare, should be considered in the differential diagnosis of PLS.

Detection and Quantification of Free Radicals in Peroxisomal Disorders: A Comparative Study with Oxidative Stress Parameters.

INTRODUCTION: Free radicals have been thought to participate in pathogenesis of peroxisomal disorders. OBJECTIVE: The aim of the work is to detect free oxide radicals in blood of patients with peroxisomal disorders and to study their relation with various oxidative stress parameters. MATERIALS AND METHODS: Twenty patients with peroxisomal disorders and 14 age and sex matched healthy subjects were included in the study. Patients with peroxisomal disorders were subdivided according to diagnosis into peroxisomal biogenesis disorders and single enzyme deficiency. Oxidative stress was evaluated in both patients and control subjects by assessment of free radicals, malondialdehyde, nitric oxide metabolites and superoxide dismutase. RESULTS: There was increase in free radicals, malondialdehyde, nitric oxide metabolites in patients compared with control subjects. However, there was decrease in superoxide dismutase levels in patients compared with control subjects. CONCLUSION: We concluded that there is excess free radicals production accompanied with decrease in antioxidant defenses in patients with peroxisomal disorders. These results strongly support a role of free radicals in the pathophysiology of peroxisomal disorders and strengthen the importance of oxidative stress phenomenon in peroxisomal disorders pathogenesis.