Fatty Acid Oxidation Disorders
Organic Acid Disorders

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Disease Name Late-onset glutaric acidemia, type 2
Alternate name(s) Glutaric aciduria, type II, Glutaric aciduria IIB, Glutaric aciduria IIC, Multiple acyl-CoA dehydrogenase deficiency, Ethylmalonic-adipidic aciduria, Electron transfer flavoprotein deficiency, Electron transfer flavoprotein dehydrogenase deficiency, ETFA deficiency, ETFB deficiency, ETFDH Deficiency
Acronym GA2, GAII, MAD, MADD
Disease Classification Fatty Acid Oxidation Disorder
Organic Acid Disorder
Variants Yes
Variant name

Glutaric acidemia type II (early onset)

Symptom onset Late infancy, childhood and early adulthood

There are three different phenotypes that stay consistent within families – neonatal onset with congenital abnormalities, neonatal onset without anomalies and mild or late onset disease. Phenotype is most likely related to the amount of residual enzyme activity. Those infants with the lowest residual enzyme activity are the most severely affected. Infants with higher residual enzyme activity are less severely affected.

Neonatal onset with congenital anomalies: See GA2 factsheet

Neonatal onset without anomalies: See GA2 factsheet

Mild or late-onset GA2: Symptoms are very variable in course and age of presentation. They include episodes of hypoketotic hypoglycemia and hepatic dysfunction. There is progressive lipid storage myopathy and carnitine deficiency and a few individuals have had progressive extrapyramidal movement disorders similar to GA1. There are some reports of asymptomatic adults.

Natural history without treatment Variable depending on the age of presentation and severity of symptoms.
Natural history with treatment For individuals with the milder late onset type, therapy may prevent some of the neurological findings and the carnitine deficiency.
Treatment Treatment of the severe neonatal presentations is not effective (see GA2 fact sheet). The efficacy of treatment for late-onset glutaric acidemia, type 2 is unknown. Treatment can include the following: dietary restriction of fat and protein, riboflavin supplementation, carnitine supplementation and glycine supplementation.
Other Sweaty foot odor has been reported. Urine organic acids may only be abnormal during acute episodes. Mothers have been reported with HELLP syndrome. Has been implicated as a cause of SIDS.
Physical phenotype No obvious dysmorphisms have been reported. One infant presented with macrocephaly. Some individuals may present with cardiomegaly and cardiomyopathy.
Inheritance Autosomal recessive
General population incidence Unknown
Ethnic differences None known
Population N/A
Ethnic incidence N/A
Enzyme location Mitochondria
Enzyme Function Transport of electrons from the acyl-CoAs to ubiquinone (CoQ10) of the mail electron transport chain
Missing Enzyme ETFA – alpha subunit of electron transfer flavoprotein
ETFB – beta subunit of electron transfer flavoprotein
ETFDH – electron transfer flavoprotein dehydrogenase
Metabolite changes Increased glutaric, lactic, ethylmalonic, butyric, isobutyric, 2-methylbutyric and isovaleric acids.
Gene Three separate genes can cause the same disorder – ETFA, ETFB, and ETFDH. Individuals with late-onset glutaric academia, type 2 appear to have varying amounts of residual enzyme activity.
Gene location ETFA – 15q23-q25
ETFB – 19q13.3
ETFDH – 4q32-qter
DNA testing available No
DNA testing detail N/A.
Prenatal testing Yes- analyte analysis of amniotic fluid or enzyme analysis of amniocytes.
MS/MS Profile C5DC- elevated
C4; C5; C6; C8; C10- multiple elevations
C6 hexanoyl carnitine- mild elevations
C8 octanoyl-carnitine- elevated
C16; C18:1- multiple elevations
OMIM Link http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=231680

Genetests Link www.genetests.org
Support Group

Organic Acidemia Association

Save Babies through Screening Foundation

Genetic Alliance

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