1. Background

• SCAD is one of four enzymes in the mitochondria responsible for the breakdown of short-chain (C4-C6) fatty acids to 2-carbon fragments (acetyl-CoA) in the beta oxidation pathway
• there are 3 straight-chain acyl-CoA dehydrogenases to deal with long, medium, and short chain fatty acids
• LCAD, MCAD, and SCAD are all homotetramers
• there may be hepatic and skeletal muscle forms of SCAD

2. Genetic Defect

• genetic defect -> deficiency of SCAD activity -> homozygous patients are unable to mobilize large fat stores and are thus at risk for becoming hypoglycemic when stressed (i.e., during infection or fasting) during which time the long and medium acyl-CoA dehydrogenases are unable to compensate for the lack of SCAD
• the accumulation of short-chain organic acids within the mitochondria during an acute episode is toxic to other metabolic pathways (pyruvate oxidation, ATP production, electron transport, ureagenesis) and thus impairs energy production during periods of stress
• SCAD deficiency produces intramitochondrial accumulation of butyryl-CoA which is metabolized to ethylmalonyl-CoA and excreted as ethylmalonic acid
• deficiency of a skeletal muscle form of SCAD may produce a variant which presents in adulthood

1. Episodic Manifestations

• because of the low number of patients identified, the clinical features vary, are not well defined, and are not necessarily associated with episodes of stress

1. Serum

• wide anion gap metabolic acidosis (anion = dicarboxylic acid)
• hypoketotic hypoglycemia
• secondary hyperammonemia
• elevated urea, uric acid, transaminases
• secondary carnitine deficiency

2. Urine

3. Diagnosis

• deficiency of SCAD activity in leukocytes and cultured skin fibroblasts
• prenatal:
  • deficiency of SCAD activity in cultured chorionic villi or amniocytes

1. Supportive

• a chronic disease with a life-long risk of episodes of hypoketotic hypoglycemia and thus must:
  • provide long-term follow-up
  • moniter serum glucose (for hypoglycemia)
  • coordinate a multidisciplinary approach:
    • Paediatrics, Neurology, Dietery, Genetics, Metabolics
  • plan for acute episodes
  • provide a medic alert bracelet

2. Goals of Therapy

• symptomatic control of and avoidance of acute episodes (stress)
• not curative

3. Diet

4. Carnitine Therapy

• 100 mg/kg/day po
• for secondary carnitine deficiency