Mutational spectrum of smith-lemli-opitz syndrome patients in hungary.

Smith-Lemli-Opitz (SLO) syndrome is an autosomal recessive disorder characterized by multiple congenital abnormalities and mental retardation. The condition is caused by the deficiency of 7-dehydrocholesterol reductase (DHCR7) which catalyzes the final step in cholesterol biosynthesis. Biochemical diagnosis is based on increased concentration of 7-dehydrocholesterol (7-DHC) in the patient serum. Both life expectancy and quality of life are severely affected by the disease. The estimated prevalence of SLO syndrome ranges between 1:20,000 and 1:40,000 among Caucasians. Although the mutational spectrum of the disease is wide, approximately 10 mutations are responsible for more than 80% of the cases. These mutations show a large interethnic variability. There are no mutation distribution data from Hungary to date. Thirteen patients were diagnosed with SLO syndrome in our laboratory. As first-line tests, serum 7-DHC and total cholesterol were measured and, in positive cases, molecular genetic analysis of the DHCR7 gene was performed. Complete genetic background of the disease could be identified in 12 cases. In 1 case only 1 mutation was detected in a heterozygote form. One patient was homozygous for the common splice site mutation c.964-1G>C, while all other patients were compound heterozygotes. One novel missense mutation, c.374A>G (p.Tyr125Cys) was identified.

Urinary N-acetyl-beta-D-glucosaminidase in epileptic children treated with antiepileptic drugs.

AIM: To investigate the effect of prolonged use of antiepileptic drugs on renal function in children. METHODS: Prospective study of 72 children (aged 3-18 years) with epilepsy, on either monotherapy (n = 44) or combined therapy (n = 28). The length of treatment varied from 1 to 13 years. Drugs used were valproic acid, carbamazepine, ethosuximide, clonazepam, clobazepam, and vigabatrin. RESULTS: In 65 patients plasma concentrations of the drugs were in the therapeutic range. In the remaining seven, plasma concentrations were slightly high. In 33 patients urinary N-acetyl-beta-D-glucosaminidase (NAG) activity was raised. The incidence of pathological NAG indices was significantly higher in the combined therapy group than in the monotherapy group. There were also significant differences in the NAG indices of patients depending on the duration of therapy. CONCLUSIONS: Results suggest that chronic use of some antiepileptic drugs-in spite of normal blood concentrations-may alter tubular function, and the dysfunction may result in clinical symptoms. Therefore, we recommend screening of tubular function in these patients.

[Age-dependent urinary N-acetyl-beta-D-glucosaminidase activity in healthy children]. / Vizelet N-acetil-beta-D-glükózaminidáz aktivitás korfüggése egészséges gyermekekben.

Urinary N-acetyl-beta-D-glucosaminidase activity was measured in 123 healthy children aged between 1-14 years by two newly developed colorimetric procedures using MNP-GlcNAc and VRA-GlcNAc substrates and was compared to the well established PNP-GlcNAc assay. The enzyme activity was factored with the urinary creatinine concentration and expressed as NAG index. The applicability and the advantages of the new methods are discussed. The NAG values obtained with each substrate decreased with age as a result of a concomitant rise in the urinary creatinine concentration.