Diversity in the incidence and spectrum of organic acidemias, fatty acid oxidation disorders, and amino acid disorders in Asian countries: Selective screening vs. expanded newborn screening

Abstract

BackgroundExpanded newborn screening (ENBS) utilizing tandem mass spectrometry (MS/MS) for inborn metabolic diseases (IMDs), such as organic acidemias (OAs), fatty acid oxidation disorders, (FAODs), and amino acid disorders (AAs), is increasingly popular but has not yet been introduced in many Asian countries. This study aimed to determine the incidence rates of OAs, FAODs, and AAs in Asian countries and Germany using selective screening and ENBS records.Materials and methodsSelective screening for IMDs using gas chromatography–mass spectrometry and MS/MS was performed among patients suspected to be afflicted in Asian countries (including Japan, Vietnam, China, and India) between 2000 and 2015, and the results from different countries were compared. Similarly, ENBS results from Japan, South Korea, Taiwan, and Germany were compared. Additionally, the results of selective screening and ENBS in Japan were compared.ResultsAmong 39,270 patients who underwent selective screening, IMDs were detected in 1170. Methylmalonic acidemia was frequently identified in several countries, including Japan (81/377 diagnosed IMDs), China (94/216 IMDs), and India (72/293 IMDs). In Vietnam, however, β-ketothiolase deficiency was particularly frequent (33/250 IMDs). ENBS yielded differences in overall IMD rates by country: 1:8557 in Japan, 1:7030 in Taiwan, 1:13,205 in South Korea, and 1:2200 in Germany. Frequently discovered diseases included propionic acidemia (PPA) and phenylketonuria (PKU) in Japan, 3-methylcrotonyl-CoA carboxylase deficiency (MCCD) and PKU in Taiwan, MCCD and citrullinemia type I in South Korea, and PKU and medium-chain acyl-CoA dehydrogenase deficiency in Germany. Furthermore, in Japan, selective screening and ENBS yielded respective PPA frequencies of 14.7% and 49.4% among all organic acidemias.ConclusionThe incidence rates of IMDs vary by country. Moreover, the disease spectra of IMDs detected via selective screening differ from those detected via ENBS.

Application of Next-Generation Sequencing Following Tandem Mass Spectrometry to Expand Newborn Screening for Inborn Errors of Metabolism: A Multicenter Study

“…According to some studies around the world, the total incidence rates of IEM range from 1:13,205 to 1:1178. For example, the incidence of IEM is 1:2512 in Slovenia (Smon et al, 2018), 1:2700 in Australia (Estrella et al, 2014), 1:2916 in Malaysia (Yunus et al, 2016), 1:3065 in Singapore (Lim et al, 2014), 1:4300 in the USA (Frazier et al, 2006), 1:8557 in Japan, 1:13,205 in South Korea, and 1:2200 in Germany (Shibata et al, 2018). Even in China, the incidence varies greatly among regions.…”

Variable phenotypes and outcomes associated with the MMACHC c.609G>A homologous mutation: long term follow-up in a large cohort of cases

“…The cblC type ( cblC ) of combined methylmalonic acidemia and homocystinuria is the most common defect in the intracellular cobalamin metabolism pathway, characterized by variable and non-specific symptoms especially in childhood [ 1 – 3 ]. An increasing hospitalization with various presentations and a heavy financial burden per hospitalization were observed in Mainland China, while the medical resources were still relatively centralized in some districts, such as Beijing, Shanghai and Guangzhou [ 4 ].…”

False positive cases of elevated tetradecenoyl carnitine in newborn mass screening showed significant loss of body weight

“…Very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD, OMIM 201475 ) is a rare congenital metabolic disorder of fatty acid beta-oxidation, which is inherited in an autosomal recessive manner. It has a prevalence of 1:93000 births in Japan [ 1 ]. VLCAD (EC 1.3.8.9) is one of a family of acyl-CoA dehydrogenases catalyzing the dehydrogenation of long-chain fatty acids in order to produce important sources of energy, such as acetyl-CoA, which feed into the TCA cycle [ 2 , 3 ].…”