In a large consanguineous family of Turkish origin, genome-wide homozygosity mapping revealed a locus for recessive nonsyndromic hearing impairment on chromosome 14q24.3-q34.12. Fine mapping with microsatellite markers defined the critical linkage interval to a 18.7 cM region flanked by markers D14S53 and D14S1015. This region partially overlapped with the DFNB35 locus. Mutation analysis of ESRRB, a candidate gene in the overlapping region, revealed a homozygous 7 bp duplication in exon 8 in all affected individuals. This duplication results in a frame shift and premature stop codon. Sequence analysis of the ESRRB gene in the affected individuals of the original DFNB35 family and in three other DFNB35-linked consanguineous families from Pakistan revealed four missense mutations. ESRRB encodes the estrogen-related receptor beta protein, and one of the substitutions (p.A110V) is located in the DNA-binding domain of ESRRB, whereas the other three are substitutions (p.L320P, p.V342L, and p.L347P) located within the ligand-binding domain. Molecular modeling of this nuclear receptor showed that the missense mutations are likely to affect the structure and stability of these domains. RNA in situ hybridization in mice revealed that Esrrb is expressed during inner-ear development, whereas immunohistochemical analysis showed that ESRRB is present postnatally in the cochlea. Our data indicate that ESRRB is essential for inner-ear development and function. To our knowledge, this is the first report of pathogenic mutations of an estrogen-related receptor gene.

Epidemiologic studies about the prevalence of adverse drug reactions in children are scarce compared to reports in adults. To assess the prevalence of parental-reported drug allergy in 6- to 9-yr-old urban school children, we performed a cross-sectional study of 6- to 9-yr-old urban children from the eastern Black Sea region of Turkey during the year 2004, using a self-administered questionnaire by parents. Response rate was 81.6% (2855/3500). The prevalence of parental-reported drug allergy was 2.8% (81/2855). The most common parental-reported drugs were penicillins and other beta-lactams (59.3%), trimethoprim-sulfamethoxazole (11.1%), and acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs) (9.9%). The most commonly reported clinical manifestations were cutaneous (n = 76, 93.8%) followed by gastrointestinal (n = 17, 21%) symptoms. In 19 (23.5%) children, the reaction involved more than one organ system. Of these 19 children, 14 used beta-lactams. Systemic reactions were not reported with NSAIDs. Medications were taken by mouth in 88.9% of the reactions. Most of the reported allergic reactions occurred in the first day of treatment (61.7%). The reported time to reaction after the last intake of the drug was <2 h in 35 (43.2%) children and 2-24 h in 45 (55.6%). Oral reactions occurred later than reactions to parentally administered drugs. Parents of 58 children (71.6%) reported that they completely avoided the suspected culprit drug following the reaction. Relapse occurred after re-administration of the drug in 21 (25.9%) children. A diagnostic approach for drug allergy was not undertaken in any of the children. This study may provide some information about the prevalence of drug allergy, although it is based on parental perception and results are unlikely to conform well to true prevalence.

Early diagnosis of CCHF and early referral to specialised centres are important for outcome. Exceptional epidemics may be seen in future owing to ecological and environmental changes.

A 4-year-old Turkish girl was referred to our hospital with the findings of encephalopathy and pancytopenia. She had a history of severe abdominal cramps and gastrointestinal bleeding. A confused state, muscle pain and weakness, erythema-bullous and erythema-nodosum-like skin lesions, and alopecia were observed at her hospitalization. All of these symptoms resolved on follow-up. On laboratory investigation severe thrombocytopenia and leukopenia, mild anemia, a moderate increase in aspartate aminotransferase and alanine aminotransferase levels were detected. After reevaluating her medical history, it was learned that she had accidentally taken 1.3 to 1.5 mg/kg of colchicine 3 to 4 days before her first hospitalization. The possibility of misdiagnosis of colchicine intoxication should be borne in mind, and pediatricians must be aware of its toxic effects, especially in areas where patients with familial Mediterranean fever are present.

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Treatment options for Crimean-Congo haemorrhagic fever (CCHF) are limited and based on general supportive managements. Thrombocytopenia is the major risk factor of CCHF. We report our experience with high-dose methylprednisolone (HDMP). This study included five patients with CCHF. Patients were given HDMP if there were findings compatible with virus-associated haemophagocytic syndrome and the effects of HDMP were evaluated. Following this, HDMP fever subsided and platelet counts increased within 24 hours. Leukocyte counts began to increase and visceral bleedings were improved. HDMP treatment was discontinued within approximately five days. After HDMP, only one patient required blood products. HDMP is effective in CCHF, especially on fever and platelet counts. Dependency on blood products was decreased. Further controlled randomized studies with large series are needed in order to analyse the timing and duration of HDMP treatment and its effect on outcome.

and VUJ obstruction, who were treated surgically in our clinic between 1994 and 2005; we also review related published reports in English. RESULTSSurgery was used in all 14 patients over the 11-year period; only five patients had an accurate diagnosis before surgery. Six patients were diagnosed with uroradiological techniques immediately after pyeloplasty; three were diagnosed on investigating an associated anomaly later. CONCLUSIONIn children with coexisting PUJ and VUJ obstruction there are serious diagnostic problems; to prevent any deterioration in renal function due to obstruction, these anomalies require early diagnosis and treatment. For an early and accurate diagnosis, the coexistence of these two anomalies in the same ureter should be considered.

Nephrotic children are at increased risk for pneumococcal infections. Antibody responses to the currently recommended pneumococcal polysaccharide vaccine have been variable and maintenance of adequate antibody levels over time has not been well documented. In this study, we determined total IgG antibody levels against pneumococcal polysaccharides before and 1, 6, 12 and 36 months after 23-valent pneumococcal polysaccharide vaccine (PPV) administration in nine children with steroid-responsive nephrotic syndrome during remission while off corticosteroids. The baseline antibody levels were between 4 and 86 mg/l. Four weeks after vaccination, the titer increased at least twofold in all patients with a mean arithmetic value of 165.4 mg/l. At the 6th month, the levels decreased in six out of nine subjects to a mean of 94.6 mg/l. At the 36th month, the control antibody levels were below the baseline or below the early postvaccination values in four out of nine subjects. Only two patients had stable high concentrations through the study period. Our data show that nephrotic patients may not retain their antibody levels despite reasonably good initial responses to the pneumococcal vaccine and that susceptibility to infections may continue in vaccinated children.