A comprehensive HADHA c.1528G>C frequency study reveals high prevalence of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency in Poland

Isolated long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is associated with c.1528G>C substitution in the HADHA gene, since most patients have the prevalent mutation on at least one allele. As it is known that the disease is relatively frequent in Europe, especially around the Baltic Sea, and that the majority of Polish LCHADD patients originate from the coastal Pomeranian province, partly inhabited by an ancient ethnic group, the Kashubians, we aimed to determine the carrier frequency of the prevalent HADHA mutation in various districts of Poland with special focus on the Kashubian district. A total of 6,854 neonatal dried blood samples from the entire country, including 2,976 Pomeranian neonates of Kashubian origin, were c.1528G>C genotyped. Fifty-nine heterozygous carriers for the prevalent c.1528G>C substitution (41 Pomeranian children) were detected in the studied group. Our data reveal a geographically skewed distribution of the c.1528C allele in the Polish population; in the northern Pomeranian province the carrier frequency is 1:73, which is the highest frequency ever reported, whereas in the remaining regions it is 1:217. Hence, the incidence of LCHADD in Poland is predicted to be 1:118,336 versus 1:16,900 in the Pomeranian district. Despite the relative rarity of the disease, screening for LCHADD in neonates born in the northern part of Poland, especially those of Kashubian origin, is justified. Our data allow us to suggest a probable Kashubian origin of the prevalent c.1528G>C mutation.