Extractions: Laboratory investigations Infant 1 Infant 2 Mother Normal /Control Carnitine (total) not done Carnitine (free) not done Palmitate oxidation 34% of control 14% of control Palmitate Oxidation not done not done 50% of control serum cultured fibroblasts whole blood Plasma amino acids, urine organic acids, and whole-blood acylcarnitine profiles (see above) were normal in both children. In vitro probing of cultured fibroblasts of infant 1 with palmitate and linoleate revealed normal acylcarnitine intermediates (not shown above). Fibroblast palmitate oxidation was 34% and 14% of control activity in infant 1 and 2, respectively. Palmitate oxidation in whole blood was decreased in both children to 12% and 19% of control activity, respectively. Whole blood palmitate oxidation in the mother was 50% of control activity. Enzymatic analysis in cultured fibroblasts of infant 1 revealed complete absence of CPT I activity but normal activities of the enzymes involved in fatty acid oxidation. Complete CPT I activity was also confirmed in the cultured fibroblasts of patient 2. CPT II activity in patient 2 was appreciably lower than CPT II activity in his sib and normal controls. Details of investigations:
Conclusions This case report illustrates that fatty acid oxidation disorders other than LCHADdeficiency can lead to maternal complications in pregnancy, and that there is http://www.umanitoba.ca/faculties/medicine/units/biochem/coursenotes/blanchaer_t
Extractions: Conclusions The low rate of beta-oxidation of palmitate in cultured fibroblasts (see table above) and whole blood in these siblings indicates a complete deficiency of CPT I. In infant 1 the activities of the other enzymes studied were well within the normal range. The activity of CPT II in patient 2 is indeed lower than CPT II activity in his sister and normal controls, and is in the range of what is found in heterozygotes. This could imply true heterozygosity for CPT II deficiency or could be artifactual due to poor growth of cells in infant 2. Neither infant nor their mother had the common G1528C mutation that prevents long-chain fatty acid oxidation. This case report illustrates that fatty acid oxidation disorders other than LCHAD deficiency can lead to maternal complications in pregnancy, and that there is a wider range of clinical presentations of CPT I deficiency than has previously been recognized. CPT I deficiency usually presents after prolonged fasting or during intercurrent illnesses between 8 and 18 mo of age with fasting hypoketotic hypoglycemia , seizures, hepatomegaly and liver dysfunction. Classically hypoketotic hypoglycemia without dicarboxylic aciduria with a high or high-normal plasma carnitine level and normal acylcarnitine profile distinguishes this disorder from all other fatty acid oxidation defects. Although one infant with CPT I deficiency has been previously reported as presenting in the neonatal period, early presentation is most unusual.
Todd Richmond's Thesis - Defects Of Beta-oxidation In Humans of being unable to degrade fatty acids are severe. There are a number of human diseasesattributed to peroxisomal and mitochondrial betaoxidation disorders. http://cellwall.stanford.edu/thesis/thesis09.htm
Extractions: The consequences of being unable to degrade fatty acids are severe. There are a number of human diseases attributed to peroxisomal and mitochondrial beta-oxidation disorders. Peroxisomal disorders can be classified into two broad categories: assembly disorders, affecting the biogenesis of peroxisomes, and single enzyme defects (Moser and Moser, 1996). Zellweger cerebro-hepato-renal syndrome, neonatal adrenoleukodystrophy (ALD) and infantile phytanic acid storage disease are examples of diseases characterized by a decreased number or absence of peroxisomes in liver and other tissues (Watkins et al., 1989; Brown et al., 1993). The clinical features of these disorders include dimorphic features, retinopathy, hypotonia, seizures, neuronal migration defects, liver disease and demyelination. Multiple biochemical abnormalities are observed as well, including the accumulation of very long chain fatty acids (VLCFA) (Moser et al., 1984). There are at least 10 disorders caused by the loss of a single peroxisomal enzyme (Moser and Moser, 1996). Deficiencies in beta-oxidation enzymes include X-linked adrenoleukodystrophy, and deficiencies of acyl-CoA oxidase, bifunctional enzyme, and peroxisomal thiolase. X-linked adrenoleukodystrophy is caused by the loss of a single bifunctional protein acting in the beta-oxidation pathway. This deficiency causes disease symptoms similar to Zellweger syndrome or neonatal ALD, both assembly disorders (Watkins et al., 1989). Peroxisomal bifunctional enzyme deficiency results in multiple biochemical abnormalities including elevated levels of very long chain fatty acid levels in both plasma and fibroblasts, impaired beta-oxidation in cultured fibroblasts, and abnormal bile acid metabolism (Watkins et al., 1989).
Pulmonary Disease Projects PKU. disorders of fatty Acid oxidation. Back GTC Research. Project PKU. Phil Laipis,Ph.D. Project disorders of fatty Acid oxidation. Terry Flotte, MD. http://www.gtc.ufl.edu/gtc-rpmeta.htm
NewScreen - Disorders Tested For In NewScreen Propionic Acidemia (PA) Acute onset Late onset. fatty Acid oxidation DisordersCarnitine/Acylcarnitine Translocase Deficiency (TRANSLOCASE); http://www.newscreentest.com/aboutnewscreen/disorders_tested.htm
Extractions: Carnitine/Acylcarnitine Translocase Deficiency (TRANSLOCASE) 3-Hydroxy Long Chain Acyl-CoA Dehydrogenase Deficiency (LCHAD) Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCAD) Multiple Acyl-CoA Dehydrogenase Deficiency (MADD or Glutaric Acidemia-Type II) Neonatal Carnitine Palmitoyl Transferase Deficiency-Type II (CPT-II) Short Chain Acyl-CoA Dehydrogenase Deficiency (SCAD) Short Chain Hydroxy Acyl-CoA Dehydrogenase Deficiency (SCHAD) Trifunctional Protein Deficiency (TFP Deficiency) Very Long Chain Acyl-CoA Dehydrogenase Deficiency (VLCAD)
Physicians Only-What Is Carnitine Deficiency? intermediates in the mitochondria. These include fatty acid oxidation disordersand amino acid oxidation defects. In these disorders, plasma http://www.carnitor.com/PhysOnly/PhysWhatIsCarnDef.html
Extractions: What is Carnitine Deficiency TPN Professionals Metabolic Professionals Nephrology Professionals ... Patient Resources What is Carnitor? What is carnitine deficiency? TPN Professionals Metabolic Professionals ... Safety Information Carnitine deficiency can be defined as a state of carnitine concentration in plasma or tissues that is below the requirement for the normal function of the organism. In clinical practice, plasma levels are commonly used to diagnose carnitine deficiency, however, these values do not always reflect the tissue carnitine concentrations. What is carnitine? Carnitine plays an integral role in the Krebs Cycle by assisting with beta oxidation. Carnitine deficiency is caused by: Professionals who provide total parenteral nutrition (TPN) or hemodialysis , or treatment for metabolic disorders or epilepsy should be especially vigilant, as these areas of treatment can result in carnitine deficiency in patients.
Volume 95, Number 6, June 2000 It now seems likely that there may other fatty acid oxidation disorders, whichare discovered in the infants of women whose pregnancy is marked with fatty http://www-east.elsevier.com/ajg/issues/9506/ajg2129dis.htm
Extractions: Page Liver Disease in Pregnancy Necessitates a Call for the Pediatrician D. R. Mack, M.D. Innes AM, Seargeant LE, Balachandra K, et al. Hepatic carnitine palmitoyltransferase I deficiency presenting as maternal illness in pregnancy. Pediatr Res 2000;47:43-5. During pregnancy, some women may develop acute fatty liver of pregnancy and a syndrome characterized by hemolysis, elevated liver enzymes, and low platelets (HELLP) for which the gastroenterologist may be consulted. Recent reports have found that a specific mutation causing L-3-hydroxylacyl-CoA dehydrogenase deficiency (LCHADD) in infants is associated with the development of these maternal pregnancy-related liver problems (NEJM 1999;340:1723-31). The report by Innes et al . describes carnitine palmitoyltransferase I deficiency (CPT I) in two siblings whose mother suffered in the first pregnancy from elevated liver function tests, prolonged PT and fatty liver and in the second pregnancy with hyperemesis gravidarum. Both CPT I and LCHADD are inherited autosomal recessive defects of mitochondrial fatty acid oxidation. The current report now represents the second fatty acid oxidation disorder of infants associated with maternal liver disorders during pregnancy. It now seems likely that there may other fatty acid oxidation disorders, which are discovered in the infants of women whose pregnancy is marked with fatty liver or the HELLP syndrome and possibly also in women who suffer from hyperemesis gravidarum. In addition to recognizing the serious nature of these pregnancy-related liver disorders for the mother, it is critical to be aware of the consequences for the newborn infant. Infants born with fatty acid oxidation deficiencies are at risk of substantial morbidity and mortality if untreated; however, early dietary intervention can prevent the complications associated with these disorders in the infants. Thus, it would be important to consult a pediatrician once these diagnoses are made in pregnant women so that at the birth of the infant the appropriate investigations and dietary management can be planned for and instituted immediately.
Extractions: (advertisement) Synonyms, Key Words, and Related Terms: primary carnitine deficiency, myopathic carnitine deficiency, secondary carnitine deficiency Background: Carnitine is a naturally occurring hydrophilic amino acid derivative, produced endogenously in the kidneys and liver and derived from meat and dairy products in the diet. It plays an essential role in the transfer of long-chain fatty acids into the mitochondria for beta-oxidation. Carnitine binds acyl residues and helps in their elimination, decreasing the number of acyl residues conjugated with coenzyme A (CoA) and increasing the ratio between free and acylated CoA. Carnitine deficiency is a metabolic state in which carnitine concentrations in plasma and tissues are less than the levels required for normal function of the organism. Biologic effects of low carnitine levels may not be clinically significant until they reach less than 10-20% of normal. Carnitine deficiency may be primary or secondary. Pathophysiology: Primary carnitine deficiency is caused by a deficiency in the plasma membrane carnitine transporter, with urinary carnitine wasting causing systemic carnitine depletion. Intracellular carnitine deficiency impairs the entry of long-chain fatty acids into the mitochondrial matrix. Consequently, long-chain fatty acids are not available for beta-oxidation and energy production, and the production of ketone bodies (which are used by the brain) also is impaired.
Hepatomegaly The Liver Is Responsible For Blood Storage And with such conditions as defects in carbohydrate metabolism, amino acid metabolism,organic acid disorders, and fatty acid oxidation disorders (Ryan Becker http://www.nursingsociety.org/education/SN0002_add3.html
Extractions: Hepatomegaly The liver is responsible for blood storage and filtration, secretion of bile and bilirubin, metabolism of fat/protein/carbohydrates, synthesis of blood-clotting components, detoxification of hormones, drugs, etc., storage of glycogen/iron/fat-soluble vitamins/vitamin B12. Use the browser's BACK button to return to the case study. Metabolic Acidosis Metabolic acidosis is the result of either an increased production of a strong acid or loss of a buffer base such as bicarbonate. Loss of bicarbonate accompanies loss of alkaline fluid from the small intestines (usually accompanies diarrheal disease or renal tubular disease). Abnormal production of an acid is usually associated with high lactic acid production or ketone production in the face of starvation. Metabolic acidosis is associated with significant negative base excess and compensatory hyperventilation. Anion gap is a determinant of the significance of the acidosis. High gap occurs with diabetic ketoacidosis, uremia, lactic acidosis, hypokalemia. Low anion gap occurs with hypoalbuminemia, hyperkalemia, hypercalcemia, dilution. Use the browser's BACK button to return to the case study.
Neonatology On The Web: Inborn Errors Of Metabolism fatty acid oxidation disorders, glutaric acidemia type II patients may have dysmorphicfeatures similar to Zellweger's, hypertrophic cardiomyopathy, and http://www.neonatology.org/syllabus/iem.03.html
Extractions: Algorithms for Evaluation william.wilcox@cshs.org Suspected IEM with Metabolic Acidosis, Diagnostic Flowchart The presence of metabolic acidosis is an important finding and the starting point for one of the two algorithms. If the anion gap is normal and associated with hyperchloremia, this suggests loss of bicarbonate either from the gastrointestinal tract or kidneys. The presence of renal tubular acidosis does not rule out an IEM, however. Galactosemia and Lowe's syndrome (oculocerebrorenal syndrome, an X-linked recessive disorder with congenital cataracts, proximal RTA, and mental retardation) as well as many other metabolic disorders which present later are associated with a RTA, usually a proximal RTA. RTA is often found with disorders of energy metabolism. Elevated anion gap acidosis can be divided into 3 categories depending on the presence of ketones and glucose level. Because the normal ketones (acetoacetic acid and 3-hydroxybutyrate) come from the oxidation of fatty acids, their absence associated with significant hypoglycemia can be suggestive of a fatty acid oxidation disorder. These disorders often present later in life with a Reye syndrome picture or "SIDS". The presence of ketones in the urine (may only be 1+) hypoglycemia suggests an organic aciduria or lactic acidosis. Hyperglycemia and ketonuria defines diabetes mellitus. Metabolic acidosis cannot be further differentiated without the results of the amino and organic acids. If these are normal (except for the changes found with lactic acidosis), then the lactate/pyruvate ratio and the glucose level will allow differentiation into 1) glycogen storage disease, gluconeogenesis disorders, or endocrine causes; 2) disorders of pyruvate metabolism; or 3) defects in mitochondrial energy metabolism.
TestQuestions-Lipid Catabolism: in Lipid Res. 41 197239. P. Rinaldo, D. Matern MJ Bennett (2002) fatty acid oxidation disorders, Annu. Rev. Physiol. 64 477-502. http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb2/part1/tq-fat.htm
Extractions: P. Rinaldo, D. Matern & M. J. Bennett (2002) "Fatty acid oxidation disorders," Annu. Rev. Physiol. 64: 477-502. 1. Write out the reaction sequence for one cycle of the mitochondrial pathway for b oxidation of fatty acyl CoA, giving names and structures of intermediates (substrates and products of each reaction) and names of enzymes. Explain why this reaction sequence is called the "
Mutation May Explain Some Sudden Infant Deaths infant deaths, based on the proportion of babies with SIDS whose biochemical profilesresembled those found in fatty acid oxidation disorders.2 Defects in http://www.respiratoryreviews.com/aug01/rr_aug01_mutation.html
Extractions: S OME S UDDEN I NFANT D EATHS Deletion of a gene essential for metabolizing long-chain fatty acids may explain some cases of sudden death in human infants. Newborn mice who had been genetically altered to lack the gene for mitochondrial trifunctional protein (MTP) showed no outward signs of physiological distress before sudden death, suggesting that genetic screening, in some cases, may be the best hope for targeting neonates for intervention. Knockout mouse pups completely lacking MTP had low birth weight and hypoglycemia, as well as abnormalities in serum markers of liver function. HOPE FOR INTERVENTION? References
Untitled Document derivatives by GCNPD for the diagnosis of mitochondrial fatty acid oxidationdisorders. Chromatographia. Hye-Ran Yoon. fatty Acid oxidation disorders. http://www.scllab.co.kr/ms/main11/main11.htm
Extractions: Top (SCI µîÀç ³í¹®) 1. Hong, S.P, Y0ON, H.R. , KIM., M. K Development of New Diagnostic-Method for Galactosemia using 8-Amino-2-naphthalenesulfonic acid by Reversed-Phase High Performance Liquid Chromatography Chromatographia. 53, 6, 112-117. 2001. 2. Lee, J-S, Yo on, H.R. , Coe, C.J, Yamaguchi S. A Korean girl with a-aminoadipic and a-keto adipic acidemia accompanied with elevanon of 2-hydroxy glutarate and glutarate, J Inherit Metab Dis, in press, 2001.(±¹³» ÖÊȯÀÚ, ¼¼°è¿¡¼ 15¹ø° º¸°íµÇ´Â ȯÀÚ) YOON, H.R. , Strauss, A. W. and Yoo, H.W. Sudden Death in a Korean infant with Very Long Chain Acyl-CoA Dehydrogenase Deficiency, J Inherit Metab Dis, in press, 2001 Yoon, H.R ., Paik, MJ, Shin, HS , Yu CL, Rinaldo, P. Analysis of plasma free fatty acid cyanomethy derivatives by GC-NPD for the diagnosis of mitochondrial fatty acid oxidation disorders. Chromatographia. 52, 211-216, 2000. 5. Yang, Y.J., Choi, M.H., Paik, M.J., Yoon, H.R ., Chung,B.C. Gas Chromatographic-mass Spectrometric determination of plasma saturated fatty acids using pentafluorodimthylsilyl derivatization.J. Chromatogr.742, 37-46, 2000.
Carnitine that are formed from acetyl CoA, a product of fatty acid oxidation. by inherited disordersof metabolism (eg, organic acidurias and betaoxidation disorders). http://www.nutritionfocus.com/nutrition_supplementation/relamino/Carnitine.html
Extractions: Avocado, beans, beef, brewer's yeast, brown rice bran, casein, chicken, dairy products, eggs, fish, heart, lactalbumin, lamb, legumes, liver, meat, milk, nuts, rabbit, seafood, seeds, soy, tempeh, wheat germ, whey, whole grains. Synthesized in the brain, kidneys and liver from lysine, methionine, vitamin B6, C and iron. One source estimates that the average omnivorous diet provides 100-300 mg of carnitine daily. Antihypercholesterolemic, antihyperlipoproteinemic , lowers LDL levels , increases HDL levels , reduces fat and triglyceride levels in the blood , increases tissue oxygenation, increases stress tolerance, helps convert stored body fat into energy. Carnitine helps reduce serum triglyceride levels by increasing fat utilization and increases the rate at which the liver uses fat. Carnitine may increase aerobic performance, increases the rate of lipid metabolism and conserving glycogen in muscle, test subjects received 4 g/day.
410 ILCS 240/ Phenylketonuria Testing Act for genetic and metabolic disorders, including but not limited to amino acid disorders,organic acid disorders, fatty acid oxidation disorders, and other http://www.legis.state.il.us/legislation/ilcs/ch410/ch410act240.htm
Newborn Screening Pilot Studies fatty Acid oxidation disorders Babies born with fatty acid oxidationdisorders are unable to break down stored fats into energy. http://www.idph.state.ia.us/fch/fam_serv/genetics/pilot_studies.htm
Center For Genetics - Genetic Disorders girdle muscular dystrophy is a group of inherited disorders with muscle acylCoAdehydrogenase deficiency is a rare inherited fatty oxidation disorder caused http://www.idph.state.ia.us/fch/fam_serv/genetics/gen-disorders.html
Family Matters Charles R. Roe, MD, is recruiting adults and children with documented CPT deficiencyand six other fatty acid oxidation disorders to participate in an 18month http://www.spiralnotebook.org/familymatters/
Extractions: Parents who have infants affected by the rare forms of CPT deficiency rarely have any warning of impending danger. Stunned by a sudden, life-threatening event or death of an apparently healthy baby, they are left with a deep, life-long loss and a bewildering array of complex medical and genetic questions. Some families lose multiple children before the underlying disorder is identified. According to a 1999 review by JP Bonnefont, MD, PhD, a total of 39 babies in 35 families have been reported with the three forms of CPT deficiency that affect infants. In those 35 families, CPT deficiency was also suspected in an additional 26 siblings who died suddenly. Such serial tragedies have spurred American parents to advocate broader mandatory newborn screening. In most states , newborns are routinely screened for only the most common genetic disorders such as phenylketonuria and sickle cell disease. L-CPT I deficiency and Severe Infantile CPT II deficiency
Office Of Dietary Supplements ODS Director lipid metabolism. Dr. Coates conducted some of the early studies offatty acid oxidation disorders in infants and children. With an http://ods.od.nih.gov/showpage.aspx?pageid=112
