ACADM Deficiency

ACADM is a gene which if mutated may lead to Medium chain Acyl coenzyme- A dehydrogenase deficiency (MCAD). The condition is also referred as MCAD Deficiency, Dicarboxylicaciduria due to defect in Beta-Oxidation of Fatty Acids, Nonketotic Hypoglycemia and Carnitine Deficiency due to MCAD Deficiency, Carnitine Deficiency Secondary to MCAD Deficiency and Dicarboxylicaciduria due to MCADH Deficiency.

 It is a rare genetic metabolic disorder in which all the symptoms are due to deficiency of medium chain Acyl coenzyme-A dehydrogenase which is essential in metabolism of medium chain fatty acids. The enzyme is found in liver, white blood cells or leukocytes and certain connective tissue cells which are also known as fibroblasts, heart and muscles. The enzyme is located inside the mitochondria and is involved in the fatty acid beta –oxidation. The patients are unable to metabolize C6-C10 length fatty acids. Failure to break down medium chain fatty acids can lead to the abnormal accumulation of fatty acids in the liver and the brain. Very low levels of the MCAD enzyme will even interrupt the process associated with normal metabolism of fatty acids. MCADD accounts for about three percent of SIDS (sudden infant death syndrome) deaths. In general body will metabolize the fat in the stress situation but in this disorder the fat will be metabolized only up to medium chain fatty acids and beyond that there will not be any metabolism so the body will continue to metabolize the glucose leading to the hypoglycemia.

Symptoms and Signs

• Vomiting
• Seizures
• Lethargy
• Hypoketotic hypoglycemia
• Encephalopathy
• Sudden infant death syndrome
• Coma
• Muscle weakness
• Failure to thrive
• Cerebral palsy
• Tachypnea
• Jitteriness
• Sweating

Diagnosis and Investigations

• Depressed Bicarbonate levels
• Anion Gap
• Low Blood Glucose Level
• Clinical Hypoglycemia
• Elevated blood ammonia level
• Molecular Genetic testing to identify the mutation in the gene
• Urinalysis to rule out Ketonuria
• Urine examination for organic acid profile and Acyl Carnitine excretion
• Liver function tests show raised liver enzymes and low plasma Carnitine levels

Treatment and Medications

• Frequent diet in gap of every 4-5 hours
• Carnitine administration is advised in some cases
• Maintenance of proper hydration
• Diet rich in carbohydrates and proteins and low in fat