Hereditary disorders of fat metabolism

Hereditary disorders of fat metabolism in a broader context include:


 * fatty acid transport and oxidation disorders;
 * sphingolipidoses (lipidoses, lysosomal fat storage diseases): Gaucher disease, Niemann-Pick disease, Krabbe disease, metachromatick leukodystrophy, Fabry disease, abd gangliosidoses;
 * disorders of lipoprotein metabolism;
 * disorders of peroxisome metabolism – involved, among other things, in the metabolism of very long chain fatty acids and the synthesis of ether phospholipids (plasmalogens).

The neonatal laboratory screening in the Czech Republic includes:


 * beta-oxidation disorders:
 * medium chain fatty acid acyl-CoA dehydrogenase deficiency (MCAD deficiency),
 * long chain fatty acid 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHAD deficiency),
 * very long chain fatty acid acyl-CoA dehydrogenase deficiency (VLCAD deficiency);
 * beta-oxidation transport disorders:
 * carnitine palmitoyltransferase I (CPT I) deficiency,
 * carnitine palmitoyltransferase II (CPT II) deficiency,
 * carnitine acylcarnitine translocase (CACT) deficiency.

Disorders of β-oxidation of fatty acids

 * Beta-oxidation: oxidation of fatty acids to acetyl-CoA, takes place in mitochondria;
 * contributes significantly to meeting energy needs during the starvation period;
 * a direct source of energy for heart and muscle tissue and a source of ketone bodies for the CNS;
 * more than 20 disorders are known, AR hereditary; occurrence of 1: 5000;
 * most common disorders: MCAD (Medium-Chain-Acyl-CoA Dehydrogenase) and LCHAD (Long Chain-3-OH-Acyl-CoA Dehydrogenase).


 * MCAD a LCHAD


 * clinical picture (MCAD+LCHAD): in infant and toddler age hypoketotic hypoglycemia → convulsions;
 * or Reye-like syndrome attack in impaired consciousness and hepatomegaly;
 * sudden death syndrome;
 * LCHAD: may also begin in neonates with cardiomyopathy with acute heart failure or in older children with muscle weakness, rhabdomyolysis attacks with myoglobinuria, neuropathy, progressive cardiomyopathy and retinitis pigmentosa;
 * diagnosis: neonatal screening - coupled mass spectrometry; examination of MK β-oxidation parameters in lymphocytes; enzymatic and molecular examination;
 * hypoketotic hypoglycemia, decreased carnitine;
 * LCHAD: increased creatine kinase and myoglobin in the blood after increased physical activity;
 * urine: dicarboxylic aciduria (MCAD), 3-OH-dicarboxylic aciduria + exercise-induced myoglobinuria (LCHAD);
 * liver steatosis;
 * therapy: prevention of starvation → frequent diet with fat reduction (for LCHAD + substitution of MCT oil, especially before any physical exertion); nutrition also during the night (infants and toddlers 2x / night meal with maltodextrins, older children meal 1x / night with uncooked corn starch);
 * in case of fever increase the intake of sweet drinks, in case of vomiting and diarrhea early administration of glucose;
 * prognosis: without early diagnosis, the risk of death under the picture of sudden death syndrome or Reye-like syndrome.

Related articles

 * Mitochondrial diseases / Disorders of beta oxidation and ketogenesis
 * Lipidosis
 * Disorders of lipoprotein metabolism: Famlilial hypercholesterolemia • Dyslipidemia
 * Lysosomal disorders
 * Disorders of peroxisome metabolism
 * Mitochondrial disorders of energy metabolism
 * Hereditary disorders of amino acid metabolism • Disorders of urea cycle • Organic acidura
 * Hereditary disorders of carbohydrate metabolism • Glycogenosis
 * Disorders of protein glycosylation
 * Hereditary disorders of purine and pyrimidine metabolism
 * Porphyrias