Homocystinuria in Taiwan: An inordinately high prevalence in an Austronesian aboriginal tribe, Tao

The newborn screening of homocystinuria in Taiwan has never been formally reported before. Since 1984, out of 5 million newborns screened, only 3 newborns (Han Taiwanese) suffering from homocystinuria were detected in this newborn screening program. Four mutations (p.R121L [c.362G > T], p.E176K [c.526G > A], p.V320G [c.959T > G] and p.G259D [c.776G > A]) were identified in these 3 patients. Unexpectedly, we recently found 8 patients presenting with homocystinuria in an Austronesian Taiwanese Tao tribe. Out of them, three patients participated in the newborn screening program but were unidentified by the current newborn homocystinuria (using methionine as a marker) screening. All the Tao patients are homozygous for a new p.D47E (c.141T > A) mutation. Among the 428 adult islanders screened for the D47E mutation, approximately 1 in 7.78 is a carrier of the mutation, and an estimated 1 in 240 islanders suffered from homocystinuria. This is the highest known prevalence of homocystinuria worldwide. The result of expression studies of all the mutations identified in Taiwan revealed that, except for p.D47E mutation, all mutations were severely limited in their ability to form functional tetramers. The clinical manifestations of the Tao patients varied widely, despite sharing the same mutation and very similar genetic and environmental backgrounds. Comparisons of clinical and biochemical phenotypes of these patients were presented in this report.

► Novel mutation D47E identified in Tao HCU patients causes impaired stability of CBS.
► Highest known prevalence (1/240) and carrier rate (1/7.8) of HCU are found in Tao.
► The clinical manifestations of HCU patients with D47E varied widely.
► The prevalence of D47E in northern Philippine will be an interest for future study.