Summary about Disease
Electron transfer flavoprotein deficiency (ETF deficiency), also known as glutaric acidemia type II (GA II), is a rare inherited metabolic disorder that disrupts the body's ability to process proteins and fats. This leads to a buildup of harmful substances in the body, particularly organic acids. There are three main types, with varying severity and onset.
Symptoms
Symptoms vary depending on the type of ETF deficiency.
Severe Neonatal Onset: Muscle weakness (hypotonia), breathing problems, enlarged liver (hepatomegaly), heart problems (cardiomyopathy), unusual facial features, and a distinctive odor. Many affected infants do not survive beyond the first few weeks or months of life.
Late-Onset/Milder Forms: Intermittent vomiting, lethargy, muscle weakness, enlarged liver, and episodes of metabolic crisis triggered by illness, fasting, or stress. These symptoms can appear anytime from infancy to adulthood.
Specific markers: Elevated levels of glutaric acid and other organic acids in the blood and urine are characteristic.
Causes
ETF deficiency is caused by mutations in the ETFA, *ETFB*, or *ETFDH* genes. These genes provide instructions for making proteins that are part of the electron transfer flavoprotein (ETF) complex, which is essential for breaking down certain amino acids, fatty acids, and choline. Mutations in these genes disrupt the function of the ETF complex, leading to the buildup of harmful substances. The condition is inherited in an autosomal recessive pattern, meaning 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.
Dietary Management: A low-protein, low-fat diet, supplemented with carnitine and riboflavin, may be recommended. Specific dietary adjustments will vary depending on the individual and severity of the condition.
Carnitine Supplementation: Carnitine helps remove toxic compounds from the body.
Riboflavin Supplementation: Some individuals with ETF deficiency respond well to riboflavin (vitamin B2) supplementation; this form is called riboflavin-responsive GAII.
Emergency Treatment: During metabolic crises, treatment includes intravenous fluids, glucose, and bicarbonate to correct electrolyte imbalances and acidosis.
Dialysis: In severe cases, dialysis might be necessary to remove toxic metabolites.
Is Communicable
ETF deficiency is not communicable. It is a genetic disorder caused by gene mutations passed down from parents to their children.
Precautions
Newborn Screening: Newborn screening can detect ETF deficiency, allowing for early diagnosis and treatment.
Genetic Counseling: Genetic counseling is recommended for families with a history of ETF deficiency to assess the risk of having an affected child.
Avoid Prolonged Fasting: Individuals with ETF deficiency should avoid prolonged fasting, as this can trigger metabolic crises.
Monitor for Illness: During illness, individuals with ETF deficiency should be closely monitored for signs of metabolic decompensation.
Follow Dietary Recommendations: Strict adherence to dietary recommendations is crucial for managing the condition.
How long does an outbreak last?
ETF deficiency is not an outbreak-related disease; it is a chronic, inherited condition. However, individuals with ETF deficiency may experience acute metabolic crises, which can last for several days or weeks if not properly treated. The duration of a metabolic crisis depends on the severity of the condition, the trigger, and the promptness of medical intervention.
How is it diagnosed?
Newborn Screening: Elevated levels of certain acylcarnitines in blood spots can indicate ETF deficiency.
Urine Organic Acid Analysis: This test detects elevated levels of glutaric acid and other organic acids in the urine.
Plasma Acylcarnitine Profile: Measures the levels of acylcarnitines in the blood.
Genetic Testing: Confirms the diagnosis by identifying mutations in the ETFA, *ETFB*, or *ETFDH* genes.
Clinical Evaluation: Based on clinical findings and physical examination.
Timeline of Symptoms
Severe Neonatal Onset: Symptoms typically appear within the first few days or weeks of life.
Late-Onset/Milder Forms: Symptoms can appear anytime from infancy to adulthood, often triggered by illness, fasting, or stress.
Important Considerations
Early Diagnosis and Treatment: Early diagnosis and treatment are crucial for improving outcomes and preventing complications.
Lifelong Management: ETF deficiency requires lifelong management, including dietary modifications, supplementation, and close monitoring for metabolic crises.
Individualized Treatment: Treatment plans should be individualized based on the severity of the condition and the individual's response to therapy.
Support Groups: Support groups can provide valuable information and emotional support for individuals with ETF deficiency and their families.
Emergency Protocol: Families should have a written emergency protocol to follow during metabolic crises, including information on medication dosages and when to seek medical attention.