Medium-chain acyl-CoA dehydrogenase deficiency (MCAD)
Incidence
Acyl-CoA dehydrogenase, medium chain (MCAD) deficiency is an inborn error of mitochondrial fatty acid oxidation, inherited as an autosomal recessive trait. More than 200 cases reported, common in whites due to a single mutation (K329E) observed in more than 95% of the cases. Onset early to late infancy. It is rare in the Arabian peninsula (Saudi mutation is different). May be the most common known cause of SIDS.
Clinical Characteristics
Clinically, the disease is characterised by acute episodes of hypoketotic hypoglycemia with hepatomegaly (pseudo Reye syndrome), triggered by fasting or infections, which occur generally within the two first years of life. There is no muscle nor cardiac involvement. It is a Reye-like, SIDS-like condition. May be asymptomatic. Patient have intolerance to fasting with hypoglycemia and NO KETOSIS, with seizures and coma. Mortality of first episode is 60%. They have quick and dramatic recovery with glucose infusion. Acidosis is mild (lactic type) with small base excess. Acyl-CoA dehydrogenase, medium chain (MCAD)deficiency is an inborn error of mitochondrial fatty acid oxidation, inherited as an autosomal recessive trait. MCAD is an electron transfer flavoprotein (ETF)-dependant enzyme, located in mitochondrial internal matrix. Diagnosis is suspected by a characteristic profile of urinary organic acids, plasma medium chain fatty acids and plasma acylcarnitines. A prevalent point mutation (A985G) has been identified (90% of muted alleles). The identification of this mutation and/or the measurement of MCAD activity in cultured fibroblasts allow to confirm the diagnosis. Treatment involves huge glucose infusion and eventually L-carnitine supplementation. The prognosis is good if fasting and catabolic states are avoided.
Precipitants
Fasting may lead to unexpected death.
Provocation Tests
Carnitine loading 200-400 mg/kg/day x 2 days will increase relevant acylcarnitines in blood. While in carnitine, short term fasting 6-8 hrs may further increase the same compounds. Most pathognomonic in tandem MS are C6-C10 acylcarnitines. Fasting is unable to produce ketones, but should not be done because is very risky.
Diagnostic Procedures
EB-F, EB-W, EB-liver, EB-heart, OB-F, DB-F. tandem MS. Diagnosis is suspected by a characteristic profile of urinary organic acids, plasma medium chain fatty acids and plasma acylcarnitines. For some metabolic disorders (and this is the case of MCAD), affected children may present with subtle abnormalities or even totally normal acylcarnitine profile when they are well but as soon as they are sick (fever or any other condition), the profile is tremendously modified. DNA analysis is available for MCAD and confirm the diagnosis. A single mutation (K329E) is observed in more than 95% of the cases. In cases of death, bile exam for acylcarnitines is very helpful.