The prevalence and genotype of 21-hydroxylase deficiency in the Croatian Romani population.

Objective: Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency (21-OHD) is a rare autosomal recessive disorder caused by pathological variants in the CYP21A2 gene. After a high prevalence of classic 21-OHD CAH in the Romani population was reported in the Republic of North Macedonia, we decided to estimate the prevalence of 21-OHD in Croatia and, if high, assess the possible causes and estimate the frequency of particular CYP21A2 variants. Design: Cross-sectional study. Methods: Data from a Croatian 21-OHD genetic database was reviewed, and only Romani patients were included in the study. CYP21A2 genotyping was performed using allele-specific PCR, MLPA, and Sanger sequencing. Results: According to a survey conducted in 2017, Croatia had 22,500 Romani people and six of them had a salt-wasting (SW) form of 21-OHD. All were homozygous for the c.IVS2-13A/C-G pathological variant in intron 2 and descended from consanguineous families belonging to different Romani tribes. The calculated prevalence of 21-OHD in Croatian Romani is 1:3,750, while in the Croatian general population, it is 1:18,000. Three of the six Romani patients originated from two neighboring villages in North-western Croatia (Slavonia County), as well as the seventh patient who is of mixed Romani/Croatian descent and heterozygous for the c.IVS2-13A/C-G pathological variant (not included in the prevalence calculation). Conclusion: A high prevalence of SW 21-OHD in the Croatian Romani population caused by the homozygous cIVS2-13A/C-G pathological variant was found. In addition to isolation and consanguinity, other possible reasons could be the heterozygous advantage of the CYP21A2 gene pathological variant and the bottleneck effect as a result of the Romani Holocaust in World War II.

The effect of 17 years of increased salt iodization on the prevalence and nature of goiter in Croatian schoolchildren.

Background High goiter prevalence caused by iodine deficiency (medium content 5.6 mg potassium iodide [KI]/kg of salt, median urine iodine concentration [UIC] 68 µg/L) in Croatia was observed in 1991 and 1995 when salt was iodized with 10 mg KI/kg. A new regulation introduced in 1996, specified 25 mg KI/kg of salt resulting in an increase of median UIC to 248 µg/L. Afterwards, goiter prevalence was only assessed in two small studies. Methods In this study, we investigated the prevalence and etiology of goiter in 3594 schoolchildren 17 years after an increase in salt iodization in Croatia. Thyroid size was determined by palpation in 1777 girls and 1817 boys aged 10-18 years. In goitrous children, a thyroid ultrasound and thyroid-stimulating hormone, free thyroxine (fT4), free triiodothyronine (fT3), thyroid peroxidase (TPO) and thyroglobulin (TG) antibody measurements were performed. Results Goiter was found in 32 children (0.89% vs. 2.8% in 1991, p<0.00001 and 27% in 1995, p<0.00001), simple goiter (SG) in 18/32 (56%) goitrous children vs. 126/152 (82.8%) in 1991 p<0.00001, autoimmune thyroiditis (AT) in 13/32 (40.6%) vs. 19/152 (12.5%) in 1991 p<0.0009, nodules in four: two cysts, toxic adenoma and carcinoma (in 1991 two adenomas and one cyst), Graves' disease was not found (four in 1991). Subclinical hypothyroidism was found in three children. Thyroid disease was diagnosed in four of 32 children before the investigation. Increased iodine supply decreased goiter prevalence and SG/AT ratio in goitrous patients. Conclusions As thyroid abnormalities were found in 0.89% of children and some required treatment, thyroid examination is important in apparently healthy children regardless of sufficient iodization.