Newborn Screening for Glutaric Aciduria-II: The New England Experience

Abstract

In addition to the severe form of GA-II, milder forms of GA-II and some GA-II carriers are identified by newborn screening. Some positive screens classified as FP may be affected with a milder form of the disorder. Characteristic GA-II profiles, quantified as GA-II indexes, may be utilized to predict probability of disorder and direct urgency of intervention for positive screens.

Prediction of disease severity in multiple acyl‐CoA dehydrogenase deficiency: A retrospective and laboratory cohort study

“…All reported plasma acylcarnitine profiles and 15 urinary organic acid profiles (83%) at diagnosis demonstrated abnormalities corresponding to MADD (ie, ≥1 increased metabolite indicative of MADD). The glutaric aciduria type II‐index, as defined by the New England Newborn Screening Program, could be calculated in four neonatal onset patients who all demonstrated values >0.005, corresponding to “high risk” MADD. The index score was also >0.005 in three later onset patients, while in two later onset patients it was <0.005.…”

“…Symptoms in later onset patients can also be fatal, but only in rare cases and usually associated with metabolic stress . Patients are identified through clinical presentation and in some countries also via population newborn bloodspot screening (NBS) . Treatment options include dietary fat‐ and protein‐ restrictions, fasting avoidance, and supplementation with carnitine, glycine, and riboflavin.…”

“…Treatment options include dietary fat‐ and protein‐ restrictions, fasting avoidance, and supplementation with carnitine, glycine, and riboflavin. Despite early identification and treatment, neonatal mortality remains high …”

“…[3][4][5] Patients are identified through clinical presentation and in some countries also via population newborn bloodspot screening (NBS). 6,7 Treatment options include dietary fat-and protein-restrictions, fasting avoidance, and supplementation with carnitine, glycine, and riboflavin. Despite early identification and treatment, neonatal mortality remains high.…”

“…Despite early identification and treatment, neonatal mortality remains high. 2,7,8 Several laboratory studies can be used to characterize MADD-patients, including urine organic acid analysis, plasma acylcarnitine profiling, and ultimately molecular studies to pinpoint the genetic defect. 2,9,10 Unfortunately, prognostic biomarkers that may predict disease severity are not available.…”