Summary about Disease
Multiple acyl-CoA dehydrogenase deficiency (MADD), also known as glutaric acidemia type II (GA-II), is a rare inherited metabolic disorder. It disrupts the body's ability to break down fats and certain proteins for energy, leading to an accumulation of harmful substances in the body. This deficiency stems from issues with the enzyme system involved in processing fatty acids, branched-chain amino acids, and lysine. MADD can present in different forms with varying severity, ranging from severe neonatal onset to milder adult onset.
Symptoms
Symptoms vary based on the type of MADD.
Neonatal Onset (Severe): Muscle weakness (hypotonia), breathing difficulties, enlarged liver (hepatomegaly), distinctive odor ("sweaty feet" odor), feeding difficulties, vomiting, metabolic acidosis, heart problems (cardiomyopathy), and potentially death.
Neonatal Onset (Less Severe): Similar to severe form, but symptoms may be milder.
Late-Onset (Adult): Muscle weakness, fatigue, exercise intolerance, muscle pain, episodes of metabolic crisis triggered by fasting, illness, or stress.
Causes
MADD is caused by genetic mutations in genes responsible for producing electron transfer flavoprotein (ETF) or electron transfer flavoprotein dehydrogenase (ETFDH). These proteins are critical components of the fatty acid and amino acid metabolism pathways. The most common genes affected are ETFA, ETFB, and *ETFDH*. MADD is inherited in an autosomal recessive pattern, meaning that an affected individual must inherit two copies of the mutated gene (one from each parent).
Medicine Used
Treatment focuses on managing symptoms and preventing metabolic crises. Common treatments include:
Riboflavin (Vitamin B2): Some individuals respond to riboflavin supplementation, especially those with mutations in the ETFDH gene.
L-Carnitine: Helps transport fatty acids into the mitochondria, potentially aiding in energy production and reducing toxic build-up.
Dietary Management: A low-fat, low-protein diet, with frequent meals to avoid prolonged fasting, is often recommended.
Medications to manage Metabolic Acidosis: Sodium Bicarbonate
Is Communicable
No, MADD is not communicable. It is a genetic disorder and cannot be spread from person to person.
Precautions
Precautions are focused on managing the condition and preventing metabolic crises:
Dietary Adherence: Strict adherence to the prescribed diet is crucial.
Avoid Prolonged Fasting: Frequent meals and snacks are necessary.
Prompt Treatment of Illnesses: Infections and other illnesses can trigger metabolic decompensation, requiring immediate medical attention.
Monitor for Symptoms: Awareness of early warning signs of metabolic crisis is important.
Genetic Counseling: For families with a history of MADD, genetic counseling is recommended.
How long does an outbreak last?
MADD is not an "outbreak"-type illness. It's a chronic condition. However, an episode of metabolic crisis can last for days or even weeks, requiring hospitalization and intensive treatment. The length of the episode depends on the severity and how quickly treatment is initiated.
How is it diagnosed?
Diagnosis usually involves a combination of:
Newborn Screening: Many regions screen for MADD at birth through blood tests (looking for elevated levels of specific acylcarnitines).
Urine Organic Acid Analysis: Detects abnormal levels of organic acids in the urine.
Plasma Acylcarnitine Profile: Identifies specific acylcarnitine abnormalities in the blood.
Enzyme Assay: Measures the activity of relevant enzymes in fibroblasts or other tissues.
Genetic Testing: Confirms the diagnosis by identifying mutations in the ETFA, ETFB, or *ETFDH* genes.
Timeline of Symptoms
Neonatal Onset: Symptoms can appear within the first few days or weeks of life.
Late Onset (Adult): Symptoms can emerge at any point during adulthood, often triggered by stressors like illness, fasting, or strenuous exercise.
Progression: Untreated, neonatal-onset MADD progresses rapidly and can be fatal. Later-onset MADD has a more variable course, with periods of stability interspersed with episodes of metabolic decompensation.
Important Considerations
Early Diagnosis and Treatment: Critical for improving outcomes, particularly in neonatal-onset forms.
Lifelong Management: MADD requires ongoing medical management and dietary adjustments.
Family Support: Living with MADD can be challenging, and access to support groups and resources is important.
Individual Variability: The severity of MADD can vary significantly, even among individuals with the same genetic mutation.
Emergency Protocol: Individuals with MADD and their caregivers should have a written emergency protocol outlining steps to take during a metabolic crisis.