Inborn errors fatty acids

Inborn errors of fatty acid oxidation Carnitine entry into cells and mitochondria Certain enzymes of fatty acid oxidation... 

Rinaldo P, Hahn SH, Matern D (2005) Inborn errors of amino acid, organic acid, and fatty acid metabolism. In Burtis CA, Ashwood ER, Bruns DE (eds) Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 4th edn. Saunders, St. Louis, Missouri, pp 2207-2247... 

Schmidt-Sommerfeld E, Penn D, Duran M, et al (1992) Detection and quantitation of acylcarnitines in plasma and blood spots from patients with inborn errors of fatty acid oxidation. Prog Clin Biol Res 375 355-362... 

To date there are no true inborn errors associated with essential fatty acid metabolism. However, we do know that the final step of DHA formation is the peroxisomal beta-oxidation of a homologous C24 fatty acid [7]. Consequently, patients with a generalised defect of peroxisomal function, such as Zellweger syndrome, are prone to develop deficiencies of essential fatty acids including DHA [9]. 

In mitochondria, there are four fatty acyl CoA dehydrogenase species, each of which has a specificity for either short-, mediurr-long-, or very-long-chain fatty acids. MCAD deficiency, an autos mal, recessive disorder, is one of the most common inborn errors of metabolism, and the most common inborn error of fatty add oxidation, being found in 1 in 12,000 births in the west, and 1 in 40,000 worldwide. It causes a decrease in fatty acid oxidation and severe hypoglycemia (because the tissues cannot obtain full ener getic benefit from fatty acids and, therefore, must now rely on glu cose). Treatment includes a carbohydrate-rich diet. [Note Infants are particularly affected by MCAD deficiency, because they rely for their nourishment on milk, which contains primarily MCADs. 

Sanjuijo P., Ruiz J. I., and Montejo M. (1997). Inborn errors of metabolism with a protein-restricted diet effect on polyunsaturated fatty acids. J. Inherited Metab. Dis. 20 783-789. 

Several classes of inborn errors of metabolism in addition to inborn errors of urea synthesis can cause neonatal hyperammonemia. These include organic acidurias, fatty acid oxidation defects, amino acidopathies, and mitochondrial respiratory chain disorders. All of these disorders have a number of features in common. Labor and delivery tend to be normal, and there are no predisposing risk factors. Clinical features present after 24 h of life and are progressive. They are inherited, and thus a family history of previously affected children or neonatal deaths may be present. While most are inherited in an autosomally recessive manner, ornithine tran-scarbamoylase (OTC) deficiency is X linked, and a family history of affected males in the maternal pedigree is not uncommon. 

Carnitine deficiency complicates HMG-CoA lyase deficiency and other inborn errors of metabolism, which results in organic acidemia. L-Camitine or P-hydroxy-y-trimethylammonium butyrate is a carrier molecule that transports long-chain fatty acids across the inner mitochondrial membrane for subsequent P-oxi-dation. L-Carnitine also facilitates removal of toxic metabolic intermediates or xenobiotics via urinary excretion of their acyl carnitine derivatives. Indeed, individuals with HMG-CoA lyase deficiency have been shown to excrete 3-methylgluatarylcamitine (Roe et al., 1986). In the absence of ketogenesis, the formation of the acyl carnitine derivative of 3-hydroxy-3-methylglutarate from HMG-CoA also serves to regenerate free CoA in the mitochondria and permits continued P-oxidation of fatty acids. 

Lactic acidosis occurs in two clinical settings (1) type A (hypoxic), associated with decreased tissue oxygenation, such as shock, hypovolemia, and left ventricular failure and (2) type B (metabolic), associated with disease (e.g., diabetes melUtus, neoplasia, liver disease), drugs and/or toxins (e.g., ethanol, methanol, and salicylates), or inborn errors of metabolism (e.g., methylmalonic aciduria, propionic acidemia, and fatty acid oxidation defects). Lactic acidosis is not uncommon and occurs in approximately 1% of hospital admissions. It has a mortality rate greater than 60%, which approaches 100% if hypotension is also present. Type A is much more common. 

Inborn Errors of Amino Acid, Organic Add, and Fatty Acid Metabolism 2207... 

Propionyl-CoA is an intermediary product in the metabo-hsm of four essential amino acids (isoleucine, valine, threonine, and methionine), the aliphatic side-chain of cholesterol, pyrimidines (uracd and thymine), and the final product of the [3-oxidation of odd-chain fatty acids. Under normal circumstances, propionyl-CoA first is converted by a biotin-dependent carboxylase to methylmalonyi-CoA, then to succinyl-CoA by an adenosylcobalamin-dependent mutase, leading to oxidation in the tricarboxylic acid cycle. Primary or secondary defects of these two enzymes were among the first organic acidurias to be discovered, and their natural history has been characterized perhaps better than any other inborn error of organic acid metabolism. 

Catecholamines and Serotonin Appendix Inborn Errors of Amino Acid, Organic Acid, and Fatty Acid Metabolism Inborn Errors of Amino Acid, Organic Acid, and Fatty Add Metabolism Appendix... 

The answer is b. (Murray, pp 238-249. Scriver, pp 2165-2194. Sack, pp 121—144. Wilson, pp 287—324.) In treating inborn errors of metabolism that present acutely in the newborn period, aggressive fluid and electrolyte therapy and caloric supplementation are important to correct the imbalances caused by the disorder. Calories spare tissue breakdown that can increase toxic metabolites. Since many of the metabolites that build up in inborn errors ol metabolism are toxic to the central nervous system, hemodialysis is recommended for any patient in stage II coma (poor muscle tone, few spontaneous movements, responsive to painful stimuli) or worse. Dietary therapy should minimize substances that cannot be metabolized—in this case fatty acids, since the oxidation of branched-chain fatty acids results in propionate. Antibiotics are frequently useful because meta-bolically compromised children are more susceptible to infection. 

The etiology of the syndrome is not clear, although recent reports have linked some cases of AFLP with a fetal inborn error in fatty acid metabolism. 

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