**4.4. IEM related to fatty acid oxidation**

Fatty acids are a major source of energy in heart as well as muscle. Fatty acid oxidation (FAO) is a series of four reactions occurring in mitochondria. The first step is catalyzed by four straight chain acyl coA dehydrogenases such as:


Medium chain acyl-coA dehydrogenase (MCAD) deficiency is the most common fatty acid oxidation-related disorder (1:10000 to 1:30000 in US) which is inherited in an autosomal recessive fashion (70-72). MCAD is an enzyme that catalyzes breakdown of fatty acids for energy production during long periods of prolonged fasting. Accumulation of octanoylcarnitine with Reye-like syndrome is typical clinical manifestation of this disorder (73;74). Children can exhibit severe hypoglycemia in mild illnesses. It can also lead to sudden infant like death syndrome (75). Symptoms may appear from 2 days to 6.5 years of age, however the patient can also remain asymptomatic for long time. When left undiagnosed MCAD deficiency has a mortality of 20% and 10-15% are severely handicapped. A case study of diagnosis as late as 30 years of age is reported in literature. The 30 year old man exhibited rhabdomyolysis, muscle weakness, acute encephalopathy after exertion in cold and fasting. Urine detection of carnitine led to the diagnosis of MCAD deficiency. Point mutation at position 985 in the coding region of MCAD gene was detected. 449\_452 deletion mutation is also studied. During acute episodes, symptomatic relief to overcome hypoglycemia cerebral edema, seizures or metabolic acidosis is the main line of treatment. Avoiding long periods of fasting is the best preventive measure that can be employed in cases with MCAD deficiency.

Short chain acyl coenzyme A dehydrogenase deficiency (SCAD) is another autosomal recessive disorder in mitochondrial fatty acid oxidation. It is characterized by increased C4 carnitine in plasma and ethylmalonic acid in urine. Clinical symptoms which appear early in life include developmental delay, hypotonia, epilepsy and behavioral disorders along with hypoglycemia and myopathy (76;77). Unlike MCAD deficiency, if neonatally screened and followed up it is found to remain asymptomatic, thus the clinical disease outcome of SCAD deficiency is questionable. Thus, need for treatment is not clear. Avoidance of fasting for longer hours with age appropriate diet is the only recommendation for prevention of primary manifestation. Annual checkup for growth, development is generally suggested.
