Prevalence of the c.35delG and p.W24X mutations in the GJB2 gene in patients with nonsyndromic hearing loss from North-West Romania.

OBJECTIVE: In Central and South-Eastern European countries, the most frequent mutation types responsible for congenital nonsyndromic sensorineural hearing loss (NSHL) are c.35delG and p.W24X (15-55.8% and 2.5-4.3%, respectively). The aim of the study was to determine for the first time in Romania the prevalence of c.35delG and p.W24X mutations in patients with NSHL. MATERIAL: 75 unrelated children with NSHL from Transylvania (North-West Romania). METHODS: a. Audiological examination (otoscopy, tympanogram, acoustic otoemission and tonal audiogram or auditory evoked potentials); b. detection of the c.35delG (semi-nested-PCR, RFLP and ARMS-PCR analysis) and p.W24X (ARMS-PCR analysis) mutations. RESULTS: Audiological examination allowed the diagnosis of hearing loss of various degrees: moderate in 8 patients (10.7%), severe in 14 cases (18.7%), profound in 53 patients (70.6%). The number of reported mutation cases as against the number of alleles indicates a 33.3% frequency rate for c.35delG mutation and respectively 5.3% for p.W24X mutation. All 22 patients with 35delG/c.35delG genotype (19 patients), c.35delG/p.W24X genotype (2 patients) or p.W24X/p.W24X genotype (1 patient) presented profound/severe hearing loss. CONCLUSION: Our study confirms that the frequency rate of the two mutations analyzed in patients with NSHL from North-West Romania is comparable to that seen in other Central and South-Eastern European countries. The homozygote or compound heterozygote states represent a major risk factor for profound or severe deafness. Audiological screening in newborns and genetic testing in confirmed congenital hypoacusis cases are compulsory for early therapeutic intervention (hearing prosthesis or cochlear implant) and genetic counselling.

Outcome of enzyme replacement therapy in patients with Gaucher disease type I. The Romanian experience.

AIM: This study reports the first evaluation of therapeutic response in Romanian patients with Gaucher disease type I, after therapy with Cerezyme recently became available in our country. PATIENTS AND METHODS: 24 patients (11-50 years) received Cerezyme 20-60 U/kg every two weeks for at least 18 months. Haemoglobin, platelet count, volume of the liver and spleen, plasma chitotriosidase and the severity score were assessed every 6 months; skeletal radiography and osteodensitometry were also monitored. RESULTS: Eleven patients were splenectomized before start of therapy. Eight patients had anaemia (mean haemoglobin 9.4 g/dl) and 14 patients, of whom 13 were without splenectomy, had thrombocytopenia (mean 65,692/mm3). Haemoglobin values normalized after 6 months and the platelet count increased to 147,818/mm3 after 18 months of treatment. Splenomegaly improved (mean 13.8x to 5.6x normal), hepatomegaly improved (mean 1.4x to 1.06x normal), the severity score decreased (mean 15.9 to 8.4), plasma chitotriosidase levels showed a reduction from 40,956 to 11,266 nmol/h per ml plasma. Bone disease improved clinically in all patients; bone radiography and osteodensitometry showed no further disease progress. We observed a mean weight gain of 4.3 kg, an improvement in quality of life, and the absence of therapeutic adverse events. CONCLUSIONS: Enzyme replacement therapy administered for 18 months in Romanian patients with Gaucher disease type I led to a marked improvement in haematological parameters and hepato- and splenomegaly. In the majority of patients we observed no further progress of bone disease; for an improvement in skeletal disease, a longer treatment period is required.

Interleukin 1 beta, tumour necrosis factor-alpha and interleukin 1 receptor antagonist in newly diagnosed insulin-dependent diabetes mellitus: comparison to long-standing diabetes and healthy individuals.

Interleukin 1 beta (IL-1) and tumour necrosis factor alpha (TNF) are important for the beta cell lysis in insulin-dependent diabetes mellitus (IDDM), while IL-1 receptor antagonist (IL-1ra) is considered protective by blocking the effects of IL-1. Serum concentrations and ex-vivo production of IL-1, TNF and IL-1ra were examined in 10 newly diagnosed IDDM (ND-IDDM) patients, and compared with 11 long-standing IDDM (LS-IDDM) patients and 14 healthy volunteers. Ex-vivo LPS-stimulated production of IL-1 in ND-IDDM patients was significantly increased compared with LS-IDDM patients and healthy controls, while TNF and IL-1ra synthesis did not differ significantly. IL-1ra/IL-1 ratio was significantly decreased in ND-IDDM, and returned to normal values in the LS-IDDM group. Circulating concentrations of IL-1ra in LS-IDDM patients were increased. These data suggest a proinflammatory imbalance in ND-IDDM patients and this may play an important role in beta cell loss.

[Pathogenetic forms of intersexuality states in children]. / Forme patogenetice ale starilor de intersexualitate la copil.

The present paper reports on 26 children with intersexuality states, belonging to the following pathologic forms: 1. female pseudohermaphroditism--11 cases, including a) type I congenital corticoadrenal hyperplasia (8 cases) and type III (1 case); b) iatrogenic form (1 case), and c) corticoadrenal virilizing adenoma (1 case); 2. male pseudohermaphroditism--6 cases, and 3. gonadal dysgenesis of female phenotype--9 cases of which a) Turner syndrome (6 cases); b) gonadal dysgenesis 45 XO/46 XX (2 cases) and c) Swyer syndrome (1 case). The authors emphasize the prenatal conditioned character (chromosomal or metabolic genetic diseases, congenital diseases) in the majority of the cases; they discuss the diagnostic criteria, therapeutical possibilities and prophylaxis as well as their efficiency which depends upon the moment the diagnosis is established.