Genotype-phenotype correlation in X-linked Alport syndrome.

Mutations in the COL4A5 gene cause X-linked Alport syndrome (XLAS). Understanding the correlation between clinical manifestations and the underlying mutations adds prognostic value to genetic testing, which is increasingly available. Our aim was to determine the association between genotype and phenotype in 681 affected male participants with XLAS from 175 US families. Hearing loss and ocular changes were present in 67 and 30% of participants, respectively. Average age of participants at onset of ESRD was 37 years for those with missense mutations, 28 years for those with splice-site mutations, and 25 years for those with truncating mutations (P < 0.0001). We demonstrated a strong relationship between mutation position and age at onset of ESRD, with younger age at onset of ESRD associated with mutations at the 5' end of the gene (hazard ratio 0.766 [95% confidence interval 0.694 to 0.846] per 1000 bp toward the 3' end; P < 0.0001). Affected participants with splice mutations or truncating mutations each had two-fold greater odds of developing eye problems than those with missense mutations; development of hearing impairment showed a similar trend. Hearing loss and ocular changes associated with mutations located closer to the 5; end of the gene. These strong genotype-phenotype correlations could potentially help in the evaluation and counseling of US families with XLAS.

Autosomal-dominant polycystic kidney disease in infancy and childhood: progression and outcome.

BACKGROUND: The natural history of autosomal-dominant polycystic kidney disease (ADPKD) has not been well described in children and infants. METHODS: The present study analyzed the characteristics of 46 ADPKD children diagnosed before 18 months of life (VEO) and 153 children diagnosed between 18 months of age and 18 years of age (non-VEO). RESULTS: VEO children had more cysts and larger renal volumes than non-VEO children when adjusted for age. In both VEO and non-VEO children, the presence of signs or symptoms at the time of diagnosis as well as the presence of hematuria or proteinuria at the study visit were associated with larger renal volumes. Children diagnosed early (VEO) or diagnosed due to signs or symptoms were also more likely to have high blood pressure. Two VEO children and no non-VEO children reached end-stage renal disease during follow-up. CONCLUSION: In contrast to many published case reports suggesting the occurrence of early end-stage renal disease in VEO children, the results of the present study were much more optimistic. Over 90% of the VEO children maintained preserved renal function well into childhood.

The role of hemodialysis machines dedication in reducing Hepatitis C transmission in the dialysis setting in Iran: a multicenter prospective interventional study.

BACKGROUND: Hepatitis C virus (HCV) infection is a significant problem among patients undergoing maintenance hemodialysis (HD). We conducted a prospective multi-center study to evaluate the effect of dialysis machine separation on the spread of HCV infection. METHODS: Twelve randomly selected dialysis centers in Tehran, Iran were randomly divided into two groups; those using dedicated machines (D) for HCV infected individuals and those using non-dedicated HD machines (ND). 593 HD cases including 51 HCV positive (RT-PCR) cases and 542 HCV negative patients were enrolled in this study. The prevalence of HCV infection in the D group was 10.1% (range: 4.6%- 13.2%) and it was 7.1% (range: 4.2%-16.8%) in the ND group. During the study conduction 5 new HCV positive cases and 169 new HCV negative cases were added. In the D group, PCR positive patients were dialyzed on dedicated machines. In the ND group all patients shared the same machines. RESULTS: In the first follow-up period, the incidence of HCV infection was 1.6% and 4.7% in the D and ND group respectively (p = 0.05). In the second follow-up period, the incidence of HCV infection was 1.3% in the D group and 5.7% in the ND group (p < 0.05). CONCLUSIONS: In this study the incidence of HCV in HD patients decreased by the use of dedicated HD machines for HCV infected patients. Additional studies may help to clarify the role of machine dedication in conjunction with application of universal precautions in reducing HCV transmission.

Serum zinc and its relation to bone mineral density in beta-thalassemic adolescents.

Trace elements have been considered to play critical roles in bone metabolism. This study aims at determining the serum zinc profile and its association with bone mineral density (BMD) abnormalities in thalassemic patients. In 131 transfusion-dependent beta-thalassemic patients, aged 10-20 yr, serum levels of zinc were measured by flame atomic absorption spectrophotometry (F-AAS). BMD values at the lumbar (L1-L4) and femoral neck were determined by dual X-ray absorptiometry (DXA). Dietary zinc intake and daily consumption of calcium were evaluated by a food-frequency questionnaire. Low serum zinc was found in 84.8% (in 44.7% severely low). Below -2 BMD Z-scores were observed in 68.7% and 17.6% of the patients at the lumbar and femoral regions, respectively. Female patients with severe zinc deficiency had lower lumbar BMD Z-scores in comparison to the other females (-3.26 vs -2.54). Serum zinc in females with femoral BMD Z-scores < - 2 was significantly lower by 16.4 microg/dL than other females. Our study suggests that serum levels of zinc can be lowered in the thalassemic patients and partly affect the BMD.

Metabolic and endocrinologic complications in beta-thalassemia major: a multicenter study in Tehran.

ABSTRACT : BACKGROUND : The combination of transfusion and chelation therapy has dramatically extended the life expectancy of thalassemic patients. The main objective of this study is to determine the prevalence of prominent thalassemia complications. METHODS : Two hundred twenty patients entered the study. Physicians collected demographic and anthropometric data and the history of therapies as well as menstrual histories. Patients have been examined to determine their pubertal status. Serum levels of 25(OH) D, calcium, phosphate, iPTH were measured. Thyroid function was assessed by T3, T4 and TSH. Zinc and copper in serum were determined by flame atomic absorption spectrophotometry. Bone mineral density (BMD) measurements at lumbar and femoral regions have been done using dual x-ray absorptiometry. The dietary calcium, zinc and copper intakes were estimated by food-frequency questionnaires. RESULTS : Short stature was seen in 39.3% of our patients. Hypogonadism was seen in 22.9% of boys and 12.2% of girls. Hypoparathyroidism and primary hypothyroidism was present in 7.6% and 7.7% of the patients. About 13 % of patients had more than one endocrine complication with mean serum ferritin of 1678 +/- 955 micrograms/lit. Prevalence of lumbar osteoporosis and osteopenia were 50.7% and 39.4%. Femoral osteoporosis and osteopenia were present in 10.8% and 36.9% of the patients. Lumbar BMD abnormalities were associated with duration of chelation therapy. Low serum zinc and copper was observed in 79.6% and 68% of the study population respectively. Serum zinc showed significant association with lumbar but not femoral BMD. In 37.2% of patients serum levels of 25(OH) D below 23 nmol/l were detected. CONCLUSION : High prevalence of complications among our thalassemics signifies the importance of more detailed studies along with therapeutic interventions.

Prevalence of hepatitis C infection and its risk factors in hemodialysis patients in tehran: preliminary report from "the effect of dialysis unit isolation on the incidence of hepatitis C in dialysis patients" project.

Hepatitis C virus (HCV) is the most common cause of chronic liver disease in patients with end-stage renal disease. It is more prevalent in hemodialysis (HD) patients than the general population but the exact routes of transmission are not clear. In this study, the current situation of HCV infection was assessed in eleven dialysis centers in Tehran, Iran. A total of 548 patients on maintenance HD with a mean age of 45.4 +/- 16.8 years were studied. Most of the patients were dialysed 3 times/week, each session lasting 4 to 4.5 hours. About 15% of patients had a history of having received peritoneal dialysis prior to maintenance HD and 23.6 of patients had received blood transfusion(s). The most common cause of renal failure was hypertension in 29.7% followed by diabetes mellitus in 23.2%, failed renal transplant in 19.4% and glomerulonephritis in 9.7%. HCV antibodies were measured by ELISA-III. All positive sera were tested for HCV RNA by RT-PCR. Positive HCV antibody tests were present in 19.6% of patients. In these seropositive patients, 48.6% had detectable HCV RNA. Prevalence of HCV antibody seropositivity was not different in patients with or without history of blood transfusion. The prevalence of positive HCV antibody in this study was higher than reports from Europe but lower than other countries in the region. Only 48.6% of seropositive cases were confirmed by PCR, which is lower than expected values. It seems that nosocomial transmission is the main route of infection in Iran.