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) ^[1].

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.^[2]

Disorders of β-oxidation of fatty acids[edit | edit source]

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).^[1]

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.^[1]