Glutaric aciduria, type 2

Glutaric aciduria, type 2
[[File:|250px|]]
Synonyms	Multiple acyl-CoA dehydrogenase deficiency (MADD)
Pronounce	N/A
Specialty	Medical genetics
Symptoms	Hypotonia, metabolic acidosis, hypoglycemia
Complications	N/A
Onset	Neonatal or later in life
Duration	N/A
Types	N/A
Causes	Genetic mutations in ETFA, ETFB, or ETFDH
Risks	N/A
Diagnosis	Genetic testing, biochemical analysis
Differential diagnosis	N/A
Prevention	N/A
Treatment	Dietary management, riboflavin supplementation
Medication	N/A
Prognosis	Variable
Frequency	N/A
Deaths	N/A

Glutaric aciduria, type 2 (GA2), also known as multiple acyl-CoA dehydrogenase deficiency (MADD), is a rare genetic disorder that affects the body's ability to break down certain fats and proteins. This condition is part of a group of disorders known as organic acidemias.

Pathophysiology

GA2 is caused by mutations in the ETFA, ETFB, or ETFDH genes, which encode components of the electron transfer flavoprotein (ETF) and ETF dehydrogenase. These proteins are essential for the proper functioning of multiple acyl-CoA dehydrogenases, enzymes that play a critical role in the mitochondrial fatty acid oxidation pathway. When these enzymes are deficient or dysfunctional, the body cannot effectively metabolize certain fats and proteins, leading to the accumulation of organic acids and other toxic substances in the body.

Clinical Presentation

The clinical presentation of GA2 can vary widely, ranging from severe neonatal forms to milder late-onset forms.

Neonatal Form

The neonatal form of GA2 is characterized by:

• Severe hypotonia
• Metabolic acidosis
• Hypoglycemia
• Hepatomegaly
• Cardiomyopathy
• Congenital anomalies

Late-Onset Form

The late-onset form may present with:

• Muscle weakness
• Exercise intolerance
• Episodes of hypoglycemia
• Rhabdomyolysis

Diagnosis

Diagnosis of GA2 is based on clinical symptoms, biochemical analysis, and genetic testing. Biochemical tests may reveal elevated levels of certain organic acids in the urine, while genetic testing can confirm mutations in the ETFA, ETFB, or ETFDH genes.

Treatment

Management of GA2 involves dietary modifications to avoid fasting and reduce the intake of fats and proteins that the body cannot metabolize. Supplementation with riboflavin (vitamin B2) can be beneficial, especially in patients with riboflavin-responsive forms of the disorder. In some cases, carnitine supplementation may also be recommended.

Prognosis

The prognosis for individuals with GA2 varies depending on the severity of the condition and the effectiveness of treatment. Early diagnosis and management can improve outcomes, particularly in milder forms of the disorder.

Also see

• Organic acidemia
• Fatty acid oxidation disorder
• Metabolic disorder
• Genetic testing