Summary about Disease
Glutaric acidemia type 2 (GA2), also known as multiple acyl-CoA dehydrogenase deficiency (MADD), is a rare inherited metabolic disorder that prevents the body from properly breaking down fats, proteins, and carbohydrates for energy. This can lead to a buildup of harmful substances, particularly organic acids, in the body. GA2 exists in varying degrees of severity, ranging from a severe neonatal form to a milder adult-onset form.
Symptoms
Symptoms vary depending on the form and severity of GA2. Common symptoms include:
Neonatal-onset (severe): Hypotonia (poor muscle tone), lethargy, poor feeding, vomiting, distinctive odor (sweaty feet-like), enlarged liver (hepatomegaly), heart problems (cardiomyopathy), breathing difficulties, metabolic acidosis, and seizures. Often fatal in infancy.
Late-onset (milder): Muscle weakness, fatigue, vomiting, diarrhea, low blood sugar (hypoglycemia), enlarged liver, heart problems (cardiomyopathy), and episodic metabolic crises triggered by illness or stress.
Other possible symptoms: Abnormal urine smell, developmental delay, coma.
Causes
GA2 is caused by mutations in genes that provide instructions for making proteins involved in the breakdown of fats and amino acids. These genes typically include ETFA, *ETFB*, and *ETFDH*. Mutations in these genes disrupt the function of the electron transfer flavoprotein (ETF) and ETF-coenzyme Q oxidoreductase, which are essential for the proper function of several enzymes involved in fatty acid oxidation and amino acid metabolism. GA2 is inherited in an autosomal recessive pattern, meaning that both parents must carry a copy of the mutated gene for their child to be affected.
Medicine Used
Treatment focuses on managing symptoms and preventing metabolic crises. Medications may include:
Riboflavin (vitamin B2): Some individuals with GA2, especially those with mutations in the ETFDH gene, respond to riboflavin supplementation.
Carnitine: Helps to remove excess acyl-CoA compounds from the body.
Glycine: May help reduce the levels of certain toxic metabolites.
Other vitamins and supplements: May be recommended by a metabolic specialist.
Is Communicable
No, Glutaric acidemia type 2 is not communicable. It is a genetic disorder and cannot be spread from person to person.
Precautions
Precautions focus on managing the condition and preventing metabolic crises:
Dietary management: A low-protein, low-fat diet is usually recommended. Specific dietary recommendations will vary depending on the individual and the severity of the condition.
Frequent feedings: Infants and young children may need frequent feedings to prevent hypoglycemia.
Avoidance of prolonged fasting: Fasting can trigger metabolic crises.
Prompt treatment of illness: Infections and other illnesses can trigger metabolic crises and require prompt medical attention.
Monitoring of blood glucose and ketone levels: Important for early detection of metabolic imbalance.
Emergency protocol: Having a written emergency plan with specific instructions for healthcare providers during a crisis.
How long does an outbreak last?
The concept of an "outbreak" does not apply to GA2. Instead, individuals may experience metabolic crises, which are acute episodes of metabolic imbalance triggered by illness, stress, or fasting. The duration of a metabolic crisis can vary from a few hours to several days, depending on the severity of the condition, the promptness of treatment, and the underlying trigger.
How is it diagnosed?
Diagnosis typically involves:
Newborn screening: Many states include GA2 in their newborn screening programs, which involves testing a blood sample shortly after birth. Elevated levels of certain acylcarnitines may suggest GA2.
Urine organic acid analysis: Elevated levels of glutaric acid and other organic acids in the urine may indicate GA2.
Plasma acylcarnitine profile: Measures the levels of various acylcarnitines in the blood.
Fibroblast enzyme assay: Measures the activity of ETF and ETF-QO in cultured skin cells (fibroblasts).
Genetic testing: Confirms the diagnosis by identifying mutations in the ETFA, *ETFB*, or *ETFDH* genes.
Timeline of Symptoms
The timeline of symptoms depends on the type and severity of GA2:
Neonatal-onset (severe): Symptoms typically appear within the first few days or weeks of life.
Late-onset (milder): Symptoms may not appear until infancy, childhood, or even adulthood. The onset can be triggered by illness, stress, or fasting. Symptoms are often episodic.
Important Considerations
Early diagnosis and treatment are crucial: Early intervention can significantly improve outcomes, especially in the severe neonatal form.
Lifelong management is required: Individuals with GA2 need ongoing monitoring and management to prevent metabolic crises and maintain optimal health.
Genetic counseling is recommended: Families with a history of GA2 should seek genetic counseling to understand the risks of recurrence and discuss reproductive options.
Support groups: Connecting with other families affected by GA2 can provide valuable emotional support and practical advice.
Consultation with a metabolic specialist is essential: Management of GA2 requires expertise in metabolic disorders.