Background: Classic 21-hydroxylase deficiency (21HD) presents some traits of the metabolic syndrome. Aim: To characterize discrete alterations of lipid and carbohydrate metabolism in children and young adults with classic 21HD, which could predict early atherogenesis. Patients and Methods: Twenty-seven Caucasian patients with classic 21HD (4–31 years); 27 sex-, age- and BMI-matched controls. Clinical parameters, hormonal status and genotype were assessed in all patients. Lipid parameters, including relative (%) and absolute (mg/dl) small-dense low-density lipoproteins subfractions (sd-LDL) were measured in patients and controls. Oral glucose tolerance tests were performed in both groups. Results: sd-LDL (%) was significantly higher in patients than controls (39.7 ± 5.9 vs. 35.5 ± 5.7%; p = 0.008). The same applies for absolute sd-LDL (mg/dl) (42.6 ± 11.9 vs. 36.4 ± 7.5; p = 0.029). HDL-cholesterol was lower in patients (p = 0.032). Fasting glucose and insulin were significantly higher in patients. Similar differences were noticed for HOMA-IR (p = 0.001), IRI (p = 0.001) and HOMA-B (p = 0.002). IRI correlated directly and significantly with the total hydrocortisone dose and the duration of treatment. Fasting glucose correlated with absolute sd-LDL. No obvious differences were seen between clinical forms or genotype groups. Conclusions: Substitution therapy should be adapted particularly at young ages to prevent early atherogenesis and cardiovascular risk in later life.

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Gaucher disease (GD) is an inherited glycolipid storage disorder resulting from the deficiency of glucocerebrosidase. It is the most frequent lysosomal storage disease in Romania, accounting for 70% of all lysosomal disorders diagnosed since 1997 in this country. The prevalence of six common mutations (N370S, L444P, R463C, 84GG, recNciI and recTL) and their phenotypic impact were studied in 20 type 1 GD patients of non-Jewish origin. Mutation analysis identified 77.8% of the GD alleles. The N370S mutation had the highest prevalence (50%), followed by the L444P (22.2%) and the recNciI (5.6%) alleles. Mutations R463C, 84GG and recTL have not been found in our patients. Rare or novel mutations likely accounted for 22.2% of the disease-producing uncharacterised alleles. Our study indicates a high prevalence of type 1 among Romanian GD patients. Clinical phenotype and disease severity were evaluated according to the standardised severity score index. Genotype -phenotype correlations were similar to those reported for other Caucasian non-Jewish populations. The absence of neuronopathic disease in patients presenting at least one copy of the N370S allele was confirmed, but the relative mildness of N370S homozygotes was not a constant feature among our patients. The presence of the L444P or of uncharacterised sporadic mutations was always associated with severe clinical manifestations, even in compound heterozygotes with the N370S allele. A large degree of phenotypic variability was observed in patients displaying the same genotype. The particularities of genotype -phenotype correlations may suggest the impact of other genetic or non-genetic factors on the clinical picture.

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