BabyScreen+ newborn screening

Gene: ETFDH

Green List (high evidence)

Well established gene-disease association.

Glutaric aciduria II (GA2) is an autosomal recessively inherited disorder of fatty acid, amino acid, and choline metabolism. It differs from GA I in that multiple acyl-CoA dehydrogenase deficiencies result in large excretion not only of glutaric acid, but also of lactic, ethylmalonic, butyric, isobutyric, 2-methyl-butyric, and isovaleric acids.

The heterogeneous clinical features of MADD fall into 3 classes: a neonatal-onset form with congenital anomalies (type I), a neonatal-onset form without congenital anomalies (type II), and a late-onset form (type III). The neonatal-onset forms are usually fatal and are characterized by severe nonketotic hypoglycemia, metabolic acidosis, multisystem involvement, and excretion of large amounts of fatty acid- and amino acid-derived metabolites. Symptoms and age at presentation of late-onset MADD are highly variable and characterized by recurrent episodes of lethargy, vomiting, hypoglycemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occurs. The organic aciduria in those with the late-onset form of MADD is often intermittent and only evident during periods of illness or catabolic stress.

Treatment: riboflavin, carnitine, glycine, Coenzyme Q10 supplementation, fat restriction, avoidance of fasting, and a diet rich in carbohydrates

Non-genetic confirmatory testing: Plasma acylcarnitine profile, Urine organic acid analysis

Created: 3 Oct 2022, 12:55 a.m. | Last Modified: 3 Oct 2022, 12:55 a.m.

Panel Version: 0.272

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Glutaric acidemia IIC, MIM# 231680

Publications

• 31904027

Green List (high evidence)

is on the current VCGS newborn screening panel

Created: 26 Sep 2022, 2:24 a.m. | Last Modified: 26 Sep 2022, 2:24 a.m.

Panel Version: 0.199

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal