A breast fed comatosed infant was brought to ER. his investigation revealed hypoketotic hypoglycemia, high concentration of medium chain carboxylic acid, acyl carnitine and acyl glycine in plasma and urine. Hyperammonemia was also present. He was diagnosed as a case of medium chain fatty acyl coA dehydrogenase deficiency.
Test name Units Normal values
blood glucose 2.5 mmol/L 6.1 mmol/L
plasma Ammonia 120 micromol/L 15-18 micromol/L
 Significance of Age
Symptoms of MCAD deficiency start appearing at approx from 2nd month to 2nd year but in some case on 2nd day of birth. Causes of this includes following reasons:
1. During first few days after pregnancy, breast milk contain mainly colostrum which is rich in protein and required for functioning of digestive tract. As the time progress the fatty content of breast milk become more fatty up to 55% of fats it contains. thats why symptoms starts appearing after approximately 2 month
Is mainly due to decrease in beta oxidation of medium chain fatty acids (abundant type of fatty acids present in milk) due which less acetyl coA is synthesized and hence the less ketone bodies.
Is mainly due to two causes
1. decrease in availability of glucogenic substances which is mainly due decrease metabolism of fatty acids.
2. decrease in mitochondrial acetyl co A down regulates the pyruvate carboxylase enzyme which is involved in the gluconeogenesis.
 Acyl carnitine and acyl glycine
Raised levels of these substances shows a type of body compensation by binding of medium chain fatty acid with carnitine and glycine. The products of this reaction are acyl carnitine and acyl glycine and excreted in urine quite easily as compared to free fatty acids
 Hyper ammonemia
Two possible causes of hyper ammonemia
1. due to increased metabolism of protein to fulfill the body requirement of glucose
2. due to octanoic acid a medium chain fatty acid and a mitochondrial toxin it causes disruption of ammonia metabolism leads to increased level of ammonia in blood.
Two possible reason for the coma
1. toxicity of ammonia which leads to impaired citric acid cycle leading to coma and hypoglycemia by decrease in energy production.
2. octanoate reduce oxidation of glucose and leads to neurological symptoms
it is an autosomal recessive disorder therefore no gender discrimination present in disease
Genetic bases of disease
this disease, the MCAD deficiency has frequency of 1 in almost 17000.
Most probable mutation is A985G type which is 985 gene of cDNA and the locus for this gene is 1p31 i.e short arm of 1st chromosome at locus no 31. In this type of mutation the adenine is replaced by guanine.
Treatment is prevention, carbohydrate rich diet and avoiding prolonged periods without glucose intake, synthetic enzyme can be injected, in extreme case IV is administered when patient is going into coma.