Fatty acids are the preferred energy source for the heart and an important energy source for skeletal muscle during prolonged exertion. Also, during fasting, the bulk of the body’s energy needs must be supplied by fat metabolism. Using fat as an energy source requires catabolizing adipose tissue into free fatty acid and glycerol. The free fatty acid is metabolized in the liver and peripheral tissue via beta-oxidation into acetyl CoA; the glycerol is used by the liver for triglyceride synthesis or for gluconeogenesis. Carnitine is required for long-chain fatty acid oxidation. Carnitine deficiencies can be primary or secondary. Secondary carnitine deficiency is a secondary biochemical feature of many organic acidemias and fatty acid oxidation defects.
There are a number of other disorders of fatty acid and glycerol metabolism, including those involving
Ketone Metabolism Disorders
Disease (OMIM Number) |
Defective Proteins or Enzymes |
Comments |
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3-Hydroxy-3-methylglutaryl-CoA synthase-2 deficiency (605911*) |
3-Hydroxy-3-methylglutaryl-CoA synthase |
Biochemical profile: See below Clinical features: Episodic nonketotic hypoglycemia, encephalopathy, hepatomegaly Treatment: Avoidance of fasting |
|
3-Hydroxy-3-methylglutaryl-CoA lyase deficiency (246450*) |
3-Hydroxy-3-methylglutaryl-CoA lyase |
Biochemical profile: Hypoglycemia, metabolic acidosis without ketonuria Clinical features: Irritability, lethargy, vomiting Treatment: Avoidance of fasting, leucine restriction |
|
Succinyl-CoA:3-oxoacid-CoA transferase deficiency (245050*) |
Succinyl-CoA 3-oxoacid-CoA transferase |
Biochemical profile: Ketonuria Clinical features: Severe episodic ketoacidosis, vomiting, hyperventilation Treatment: Glucose during acute episodes plus judicious use of bicarbonate, high-carbohydrate diet with some restriction of protein and fat |
|
Mitochondrial acetoacetyl-CoA thiolase deficiency (203750*) |
Mitochondrial acetoacetyl-CoA thiolase |
Biochemical profile: Severe metabolic acidosis, hypoglycemia, ketonuria Clinical features: Lethargy, vomiting Treatment: Avoidance of fasting |
|
Cytoplasmic acetoacetyl-CoA thiolase deficiency (614055*) |
Cytoplasmic acetoacetyl-CoA thiolase |
Biochemical profile: Ketonuria Clinical features: Intellectual disability, hypotonia Treatment: Not established |
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* For complete gene, molecular, and chromosomal location information, see the Online Mendelian Inheritance in Man® (OMIM®) database. |
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Other Fat Metabolism Disorders
Disease (OMIM Number) |
Defective Proteins or Enzymes |
Comments |
|
Sjögren-Larsson syndrome (270200*) |
Fatty aldehyde dehydrogenase |
Biochemical profile: No readily detectable plasma or urinary abnormality Clinical features: Ichthyosis, intellectual disability, spastic diplegia or tetraplegia, retinopathy, seizures Treatment: Symptomatic; topical keratolytics or systemic retinoids, reduced long-chain fat and increased medium-chain triglycerides in diet |
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* For complete gene, molecular, and chromosomal location information, see the Online Mendelian Inheritance in Man® (OMIM®) database. |
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