Glutaricaciduria II

Glutaric Aciduria Type II

Glutaric Aciduria Type II (GA II), also known as Multiple Acyl-CoA Dehydrogenase Deficiency (MADD), is a rare metabolic disorder that affects the body's ability to break down certain fats and proteins. It is an autosomal recessive disorder caused by mutations in genes that encode for enzymes involved in the mitochondrial fatty acid oxidation pathway.

Pathophysiology

GA II is characterized by a deficiency in multiple acyl-CoA dehydrogenases, which are enzymes responsible for the breakdown of fatty acids and amino acids. This deficiency leads to the accumulation of organic acids and acylcarnitines in the body, which can be toxic and result in metabolic crises.

The disorder is caused by mutations in the ETFA, ETFB, or ETFDH genes, which encode for the electron transfer flavoprotein (ETF) and ETF dehydrogenase. These proteins are essential for the transfer of electrons in the mitochondrial respiratory chain, a critical step in energy production.

Clinical Presentation

The clinical presentation of GA II can vary widely, ranging from severe neonatal forms to mild, late-onset forms. Symptoms may include:

• Hypotonia
• Hypoglycemia
• Metabolic acidosis
• Hepatomegaly
• Cardiomyopathy
• Muscle weakness

Neonatal forms often present with severe symptoms shortly after birth, while late-onset forms may present with muscle weakness and fatigue in adolescence or adulthood.

Diagnosis

Diagnosis of GA II is typically made through a combination of clinical evaluation, biochemical testing, and genetic testing. Key diagnostic tests include:

• Plasma acylcarnitine analysis
• Urine organic acid analysis
• Genetic testing for mutations in the ETFA, ETFB, or ETFDH genes

Treatment

Management of GA II involves dietary modifications and supplementation to prevent metabolic crises. Treatment strategies may include:

• A low-fat, high-carbohydrate diet
• Supplementation with riboflavin (vitamin B2), which can improve enzyme function in some patients
• Carnitine supplementation to help remove toxic metabolites

Prognosis

The prognosis for individuals with GA II varies depending on the severity of the disorder. Early diagnosis and management can improve outcomes, particularly in milder forms of the disease.

Also see

• Fatty acid oxidation disorders
• Metabolic disorders
• Mitochondrial diseases

NIH genetic and rare disease info

• NIH info on Glutaricaciduria II

Glutaricaciduria II is a rare disease.