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Primary hyperoxaluria (PH) is an autosomal recessive disorder of oxalate metabolism caused by pathogenic variants in either of three genes (AGXT, GRHPR or HOGA1). The study aimed at characterizing the clinical phenotypes as well as the genotypic spectrum of PH in Egypt. We screened 25 Egyptian patients suspected of PH for the three responsible genes by Sanger sequencing. We diagnosed 20 patients from 18 unrelated families, in which the natural history, family history, clinical features and genotypes were evaluated. PH patients were 15 males and 5 females ranging in age from 4 months to 31 years (median 8 years). Fifteen families were consanguineous (83%) and familial clustering was reported in six families (33%). Pathogenic variants in all 40 alleles were in AGXT, with none detected in GRHPR or HOGA1. We detected two novel pathogenic variants c.166-1_172dupGATCATGG (p.Asp58Glyfs*65) and c.766delC (p.Gln256fs*16) and seven previously reported variants in our cohort. This is the first study reporting the genotype of a considerable number of PH1 patients from Egypt. Our detected variants in the AGXT gene could form the basis for future genetic counseling and prenatal diagnosis in Egypt and surrounding populations.

Background Nephropathic cystinosis is an inherited autosomal recessive lysosomal storage disorder characterized by the pathological accumulation and crystallization of cystine inside different cell types. WBC cystine determination forms the basis for the diagnosis and therapeutic monitoring with the cystine depleting drug (cysteamine). The chitotriosidase enzyme is a human chitinase, produced by activated macrophages. Its elevation is documented in several lysosomal storage disorders. Although, about 6% of Caucasians have enzyme deficiency due to homozygosity of 24-bp duplication mutation in the chitotriosidase gene, it is currently established as a screening marker and therapeutic monitor for Gaucher’s disease. Methods Plasma chitotriosidase activity was measured in 45 cystinotic patients, and compared with 87 healthy controls and 54 renal disease patients with different degrees of renal failure (CKD1-5). Chitotriosidase levels were also correlated with WBC cystine in 32 treated patients. Furthermore, we incubated control human macrophages in-vitro with different concentrations of cystine crystals and monitored the response of tumor necrosis factor-alpha (TNF-α) and chitotriosidase activity. We also compared plasma chitotriosidase activity in cystinotic knocked-out (n = 10) versus wild-type mice (n = 10). Results Plasma chitotriosidase activity in cystinotic patients (0–3880, median 163 nmol/ml/h) was significantly elevated compared to healthy controls (0–90, median 18 nmol/ml/h) and to CKD patients (0–321, median 52 nmol/ml/h), P

Sirs, Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease that constitutes the most frequent genetic cause for end-stage renal disease (ESRD) in the first three decades of life. Homozygous deletions in the NPHP1 gene account for approximately 21% of all NPHP cases, whereas the other genes contribute less than 3% each. Interestingly, positional cloning of the nine genes (NPHP 1 through 9) and functional characterization of their encoded proteins (nephrocystins) have contributed to a unifying theory that defines cystic kidney diseases as “ciliopathies” [1]. Since there are no clinical or molecular data about NPHP in Egyptian children, we investigated the prevalence of homozygous NPHP1 deletion among a cohort of children with presumptive diagnosis of NPHP at Center of Pediatric Nephrology & Transplantation (CPNT), Cairo University. We studied 20 children, from 17 independent families, fulfilling the clinical and the ultrasonographic criteria of NPHP. All patients had full ophthalmologic examination, brain MRI was carried out in children with neurological involvement. Analysis for a homozygous deletion of the NPHP1 gene was performed by multiplex polymerase chain reaction (PCR) approach on genomic DNA of patients described earlier [2]. Sex distribution among affected patients showed a slight preponderance of females, with a ratio of 1.2:1 (11 females and 9 males). Seventy five percent of our study patients were the products of consanguineous marriages, the percentage of affected siblings was strikingly high 65% (13/20 patients) and 40% (8/20 patients) had a history of sibling death due to a similar condition. Fifteen of 20 patients (75%) presented with signs of ESRD. All the patients suffered from anemia and growth retardation when they first came to medical attention. Nineteen of 20 patients (95%) had a history typical of nephronophthisis, with symptoms of polydipsia, polyuria, and secondary enuresis. Four of 20 patients (20%) were hypertensive with elevated blood pressure above the 95th percentile for age, gender, and height. Clinically, study patients were best categorized as: 13/20 (65%) patients with isolated juvenile NPHP, 3/20 (15%) patients as infantile NPHP, while the remaining 4/20 (20%) patients had extrarenal associations (molar tooth sign on brain MRI, ataxia, mental retardation, retinal dystrophy, oculomotor apraxia, and facial dysmorphy) hence were clinically categorized as Joubert Syndrome Related Disorder (JSRD). The mean age at diagnosis 87.5 + 45.4 months was significantly late as compared to the age of onset of symptoms 43.8 ± 29.7 months (P