fig1

Figure 1. (A) Newborn bloodspot screening for methylmalonic acidaemia and propionic acidaemia demonstrates the differences in counting conditions by pathogenic variants or target analytes^[36]. Pathogenic variations in nine different genes result in the elevation of a single analyte such as propionylcarnitine. Although this analyte was primarily used to detect methylmalonic acidaemia caused by pathogenic variation of the MMUT gene or propionic academia related to genetic variants in PCCA and PCCB genes, methylmalonic acidaemia caused by pathogenic variants in MMAA, MMAB, MMADHC, MMACHC, LMBRD1, and ABCD4 could also be identified; (B) Newborn bloodspot screening for the target analyte 3-hydroxyisovaleryl-/2-methyl-3-hydroxy acylcarnitine (C5-OH) may identify both Category 1 “target disorders” and Category 2 “incidental findings” when elevated. Category 1 and 2 disorders categorised and defined by The Human Genetics Society of Australasia (HGSA)^[1]. Elevated C5-OH can lead to the identification of four “target disorders” and three “incidental findings.” Uncertainty exists surrounding the actionability of the latter “incidental findings”^[37,38]. *Biotinidase deficiency is screened for in New Zealand but not in Australia. Cbl: cobalamin. This figure was created using https://www.biorender.com/.