There are many inherited disorders of these processes, which typically exhibit during fasting with hypoglycemia and acidosis, some also cause cardiomyopathy and muscle weakness.
Beta-oxidation cycle disorders (see table) are among the fatty acid and glycerol metabolic disorders.
There are many inherited disorders of these processes, which typically exhibit during fasting with hypoglycemia and acidosis, some also cause cardiomyopathy and muscle weakness. Beta-oxidation cycle disorders (see table) are among the fatty acid and glycerol metabolic disorders. See also Procedure in a patient with suspected congenital metabolic disorder and investigation for suspected inherited metabolic disorders. Acetyl-CoA is generated through repeated beta-oxidation of fatty acids. To split completely long chain fatty acids, four enzymes required (a Acyldehydrogenase, a hydratase, a Hydroxyacyldehydrogenase and a lyase), which for the different chain lengths (long chains, long chains, medium-chain and short chains) are specific. The mode of inheritance for all defects of fatty acid oxidation is autosomal recessive. Disorders of fatty acid transport and mitochondrial oxidation disease (OMIM number) defects proteins or enzymes defective gene or genes (chromosomal location) Remarks primary systemic carnitine (212140) Plasmamembrankarnitintransport OCTN2 SLC22A5 (5q31,1) * biochemical profile: Elevated Karnitinausscheidung in urine despite very low carnitine in the blood; Lack of significant Dikarbonsäureazidurie Clinical features: hypoketotic hypoglycemia, Fast intolerance with hypotension, suppressed CNS, apnea, seizures, cardiomyopathy, developmental delay treatment: L-carnitine Long chain fatty acids transport deficiency (603376) – – Biochemical Profile: Low to normal free carnitine; during acute attacks increased C8-C18 Acylkarnitinester in blood Clinical features: Episodic acute liver failure, hyperammonemia, encephalopathy treatment: liver transplantation carnitine palmitoyl transferase I (CPT I) deficiency (255120) CPT-I CPT1A (11q13) * Biochemical Profile : Medium to higher total and free carnitine in the blood, no Dicarbonsäureazidurie Clinical features: Fast intolerance, hypoketotic hypoglycemia, hepatomegaly, seizures, coma, elevated creatine kinase treatment: fasting, frequent feeding; during acute episodes, high-dose glucose; Replacement of long chain fatty acids with fewer long chain fatty acids carnitine / acylcarnitine deficiency (212138) carnitine / acylcarnitine SLC25A20 (3p21,31) * Biochemical Profile: Low carnitine in the plasma, usually conjugated with long-chain fatty acids; increased C16 Karnitinester Clinical features: In the neonatal form Fast intolerance with hypoglycemic coma, vomiting, weakness, cardiomyopathy, arrhythmia, mild hyperammonemia In the mild form recurrent hypoglycemia without cardiac involvement Treatment: fasting, frequent feeding; if the plasma level is low: Karnitingabe and during acute attacks high-dose glucose carnitine palmitoyltransferase II (CPTII) deficiency (255100, 600649, 608836) CPTII CPTII (1p32) * biochemical profile: Elevated C16 -Karnitinester In classical muscular form is the Karnitinwert usually unremarkable in the severe form of Plasmakarnitinwert is low and usually conjugated with long chain fatty acids Clinical features: heavy in the classic muscular form in adulthood episodic myoglobinuria with weakness after prolonged physical effort, fasting, the onset of illness or stress When form in the neonatal period or in infancy hypoketotic hypoglycemia, cardiomyopathy, arrhythmia, hepatomegaly, Coma or convulsions Treatment: fasting, frequent feeding; if the plasma level is low: Karnitingabe and during acute attacks high-dose glucose lack of long-chain acyl-CoA dehydrogenase (VLCAD) (201475) VLCAD ACADVL (17p12-P11.1) * biochemical profile: Elevated saturated and unsaturated C14-C18-Acylcarnitinester , C6-C14 increased dicarboxylic acids in urine Clinical characteristics: the VLCAD-C-type arrhythmia, hypertrophic cardiomyopathy, sudden death in the VLCAD-H type recurrent hypoglycemia hypoketotic, encephalopathy, mild acidosis, mild hepatomegaly, hyperammonemia, elevated liver enzymes treatment: No fasting, high-carb diet; Carnitine, medium chain triglycerides, while the acute attacks high-dose glucose lack of long-chain 3-Hydroacyl-CoA dehydrogenase (LCHAD) (600890) LCHAD Hadha (2p23) * biochemical profile: Elevated saturated and unsaturated C16-C18 Acylcarnitinester, elevated C6-C14 3 -Hydroxydicarbonsäuren in urine Clinical features: Fast-induced hypoglycemia hypoketotic, exercise-induced rhabdomyolysis, cardiomyopathy, cholestatic liver disease, retinopathy, maternal HELLP syndrome treatment: fast, high-carb diet; Carnitine, medium chain triglycerides, while the acute attacks high-dose glucose at retinopathy docosahexaenoic acid may be useful lack of mitochondrial trifunctional protein (TFP) (609,015) Mitochondrial TFP biochemical profile: Similarly, LCHAD deficiency Clinical features: liver failure, cardiomyopathy, hypoglycemia after fasting, myopathy, sudden death treatment: Similar to LCHAD- lack ?-subunit Hadha (2p23) * ? subunit HADHB (2p23) * Lack of medium-chain acyl-CoA dehydrogenase (MCAD) (201450) MCAD ACADM (1p31) * biochemical profile: Elevated saturated and unsaturated C8-C10 Acylcarnitinester; increased C6-C10 dicarboxylic acids in the urine, and Suberylglyzine Hexanoylglyzine; low free carnitine Clinical features: Episodic hypoketotic hypoglycemia after fasting, vomiting, hepatomegaly, lethargy, coma, acidosis, SIDS, Reye’s Syndrome Treatment: fasting, frequent feeding, including food, just before bedtime, high-carb diet, carnitine lack of short-chain acyl-CoA dehydrogenase during acute episodes high-dose glucose (SCAD) (201470) SCAD ACADS (12q22-qter) * Biochemical profile: the neonatal form intermittent Äthylmalonsäureazidurie in the chronic form low muscular carnitine Clinical features: the neonatal form neonatal acidosis, vomiting, growth and developmental delay In the chronic form progressive myopathy treatment: fasting Glutaric aciduria type II (231680) electron-transferring flavoprotein (ETF) – biochemical profile: Elevated ethylmalonic acid, glutaric acid, 2-hydroxyglutaric acid, 3-hydroxy-isovaleric acid, and C6-C10 dicarboxylic acids and isovaleric acid in the urine; Glutarylkarnitin increased, and straight-chain Isovaleriankarnitin Acylkarnitinester of C4, C8, C10, C10: 1, C12 and fatty acids; low serum-carnitine, increased serum sarcosine Clinical features: hypoketotic after fasting hypoglycemia, acidosis, sudden death, CNS abnormalities, myopathy, possibly involvement of the liver and heart treatment: No fasting, frequent feedings; Carnitine, riboflavin, and during acute attacks high-dose glucose ?-subunit ETFA (15q23-q25) * ? subunit ETFB (19q13.3) * ETF: ubiquinone oxidoreductase (ETF: QO) ETFDH (4q32-qter) * Lack of short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) (601609) SCHAD HADHSC (4q22-q26) Biochemical profile: ketotic C8-C14-3- Hydroxydicarbonsäurenazidurie Clinical features: Recurring Myoglobinur ie, ketonuria, hypoglycemia, encephalopathy, cardiomyopathy Treatment: No fasting lack of short- and medium-chain 3-hydroxyacyl-CoA dehydrogenase (S / MCHAD) S / MCHAD – biochemical profile: Significant increase in the MCHADs and Acylkarnitine Clinical features: liver failure, encephalopathy treatment: No fasting lack of medium-chain 3-ketoacyl-CoA thiolase (MCKAT) (602199) MCKAT biochemical profile: Milchsäureazidurie, ketosis, elevated C4-C12 Dicarbonsäureazidurie (especially C10 and C12) in the urine Clinical characteristics: Fast intolerance, vomiting, dehydration, metabolis che acidosis, liver dysfunction, rhabdomyolysis Treatment: No fasting lack of 2,4-dienoyl-CoA reductase (222,745) of 2,4-dienoyl-CoA reductase DECR1 (8q21.3) * Biochemical Profile: Hyperlysinämie, low plasma carnitine, 2- trans, 4-cis Decadienoylcarnitin in blood and urine Clinical features: Neonatal hypotension, respiratory acidosis treatment: Not determined * the gene was identified and the molecular basis has been elucidated. HELLP = hemolysis, elevated liver enzymes and low platelet count; OMIM = Online Mendelian Inheritance in Man (s. OMIM database). Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) The medium Acyldehydrogenase defect (MCADD) is the most common defect in the ?-oxidation cycle and is being tested in many states in newborn screening. The clinical manifestations often start with 2-3 months of life, usually after a shorter period of fasting (12 h). Patients vomiting, and lethargy can be easy to seizures, coma and sometimes progress to death, which may look like in SIDS. During the attacks, patients have hypoglycemia, hyperammonemia and unexpectedly low urine and serum ketones. Metabolic acidosis is often present, but can also be a late manifestation. The diagnosis of MCADD can be made by determination of medium Fettsäurekonjugaten of carnitine in the blood or urine or by an enzyme deficiency in cultured fibroblasts. Most cases can be confirmed by DNA testing. The treatment of acute attacks is to i.v. administration of 10% dextrose with 1.5 times the maintenance dose (dehydration in children: maintenance requirement); Sometimes doctors recommend during the acute phases of a Karnitingabe. Prevention consists in a low-fat and high-carbohydrate diet and the avoidance of prolonged Almost episodes. The gift of corn starch is often used to have a safety margin for the night. Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) This defect is the second most common disorder of fatty acid oxidation. She has many aspects in common with the MSADD, but patients also suffer from cardiomyopathy, rhabdomyolysis, greatly increased creatine kinase, myoglobinuria with muscular effort, peripheral neuropathy, and abnormal liver function. Mothers with a LCHADD-fetus during pregnancy have often HELLP syndrome (hemolysis, elevated liver function tests, low platelet count). The diagnosis of LCHADD is provided due to the presence of long chain hydroxy acids in an organic acid analysis and the presence of their Karnitinkonjugate in a Acylcarnitinanalyse or Glyzinkonjugate in a Acylglycinanalyse. It can be confirmed by enzyme assays in skin fibroblasts. The treatment during an acute deterioration is to hydration, high doses of glucose, bed rest, and Urinalkalisierung Karnitingabe. The long-term treatment is a high-carbohydrate diet, substitution of medium chain fatty acids and avoidance of fasting and strong efforts. Defect in the degradation of very long-chain acyl-CoA dehydrogenase (VLCADD) This disorder is very similar to LCHAD defect, but is often associated with a cardiomyopathy. Glutarazidämie type II Also affected is the oxidation of various amino acids. A defect in the transfer of electrons from the coenzyme of Fettacyldehydrogenasen on the electron transport chain affects the reactions involving fatty acids of all chain lengths are involved (multiple acyl-CoA dehydrogenase defects). The clinical manifestations include a Fastenhypoglykämie, severe metabolic acidosis and hyperammonemia. The diagnosis of Type II Glutarazidämie is provided due to increased values ??for ethylmalonic acid, glutaric acid, 2- and 3-hydroxyglutaric acid and other dicarboxylic acids in the analysis of organic acids as well as elevated levels of glutaryl, isovaleryl and other acylcarnitines by tandem mass spectrometry. The enzyme deficiency in the skin fibroblasts can confirm the diagnosis. Treating a Glutarazidämie type II is similar to MCAD deficiency, except that in some patients riboflavin can be effective.