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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/05/14 19:35:05」(JST)

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Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency, often shortened to LCHAD deficiency, is a rare autosomal recessive fatty acid oxidation disorder that prevents the body from converting certain fats into energy. This can become life-threatening, particularly during periods of fasting.

Schematic demonstrating mitochondrial fatty acid beta-oxidation and effects of LCHAD deficiency

Genetics

Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency has an autosomal recessive pattern of inheritance.

Mutations in the HADHA gene lead to inadequate levels of an enzyme called long-chain 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase, which is part of a protein complex known as mitochondrial trifunctional protein. Long-chain fatty acids from food and body fat cannot be metabolized and processed without sufficient levels of this enzyme. As a result, these fatty acids are not converted to energy, which can lead to characteristic features of this disorder, such as lethargy and hypoglycemia. Long-chain fatty acids or partially metabolized fatty acids may build up in tissues and damage the liver, heart, retina, and muscles, causing more serious complications.

Symptoms

Typically, initial signs and symptoms of this disorder occur during infancy or early childhood and can include feeding difficulties, lethargy, hypoglycemia, hypotonia, liver problems, and abnormalities in the retina. Muscle pain, a breakdown of muscle tissue, and abnormalities in the nervous system that affect arms and legs (peripheral neuropathy) may occur later in childhood. There is also a risk for complications such as life-threatening heart and breathing problems, coma, and sudden unexpected death. Episodes of LCHAD deficiency can be triggered by periods of fasting or by illnesses such as viral infections.

External links

Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency at NLM Genetics Home Reference
Newbornscreening.info

UpToDate Contents

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1. 妊娠時の急性脂肪肝 acute fatty liver of pregnancy
2. HELLP症候群 hellp syndrome
3. 妊娠中に発現した肝疾患に対するアプローチ approach to liver disease occurring during pregnancy

English Journal

L-carnitine supplementation as a potential antioxidant therapy for inherited neurometabolic disorders.

Ribas GS, Vargas CR, Wajner M.Author information Federal University of Rio Grande do Sul, Brazil; Serviço de Genética Médica, HCPA, Ramiro Barcelos 2350, Porto Alegre, RS 90035-903, Brazil.AbstractIn recent years increasing evidence has emerged suggesting that oxidative stress is involved in the pathophysiology of a number of inherited metabolic disorders. However the clinical use of classical antioxidants in these diseases has been poorly evaluated and so far no benefit has been demonstrated. l-Carnitine is an endogenous substance that acts as a carrier for fatty acids across the inner mitochondrial membrane necessary for subsequent beta-oxidation and ATP production. Besides its important role in the metabolism of lipids, l-carnitine is also a potent antioxidant (free radical scavenger) and thus may protect tissues from oxidative damage. This review addresses recent findings obtained from patients with some inherited neurometabolic diseases showing that l-carnitine may be involved in the reduction of oxidative damage observed in these disorders. For some of these diseases, reduced concentrations of l-carnitine may occur due to the combination of this compound to the accumulating toxic metabolites, especially organic acids, or as a result of protein restricted diets. Thus, l-carnitine supplementation may be useful not only to prevent tissue deficiency of this element, but also to avoid oxidative damage secondary to increased production of reactive species in these diseases. Considering the ability of l-carnitine to easily cross the blood-brain barrier, l-carnitine supplementation may also be beneficial in preventing neurological damage derived from oxidative injury. However further studies are required to better explore this potential.
Gene.Gene.2014 Jan 10;533(2):469-76. doi: 10.1016/j.gene.2013.10.017. Epub 2013 Oct 19.
In recent years increasing evidence has emerged suggesting that oxidative stress is involved in the pathophysiology of a number of inherited metabolic disorders. However the clinical use of classical antioxidants in these diseases has been poorly evaluated and so far no benefit has been demonstrated
PMID 24148561

[Interaction mechanism and influence between fatty acid oxidation and p38MAPK signal transduction pathway in trophoblast cells incubated with fatty acids].

Sun XL1, Yang Z2, Wang JL1, Wang W1, Wang XY1, Wu SY1.Author information 1Department of Obstetrics & Gynecology, Peking University Third Hospital, Beijing 100191, China.2Department of Obstetrics & Gynecology, Peking University Third Hospital, Beijing 100191, China. Email: zi_yang@email.com.AbstractOBJECTIVE: To explore the interaction mechanism and influence between fatty acids oxidation and p38MAPK signal transduction pathway in trophoblast cells stimulated by fatty acids of different chain lengths.
Zhonghua yi xue za zhi.Zhonghua Yi Xue Za Zhi.2013 Dec 17;93(47):3786-90.
OBJECTIVE: To explore the interaction mechanism and influence between fatty acids oxidation and p38MAPK signal transduction pathway in trophoblast cells stimulated by fatty acids of different chain lengths.METHODS: Serum-free trophoblast cells cultured in vitro were divided into 5 groups, i.e. incub
PMID 24548400

Altered body composition and energy expenditure but normal glucose tolerance among humans with a long-chain fatty acid oxidation disorder.

Gillingham MB, Harding CO, Schoeller DA, Matern D, Purnell JQ.Author information Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, Oregon;AbstractThe development of insulin resistance has been associated with impaired mitochondrial fatty acid oxidation (FAO), but the exact relationship between FAO capacity and glucose metabolism continues to be debated. To address this controversy, patients with long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) deficiency underwent an oral glucose tolerance test (OGTT) and measurement of energy expenditure, body composition, and plasma metabolites. Compared with controls, patients with LCHAD deficiency had a trend toward higher total body fat and extramyocellular lipid deposition but similar levels of intramyocelluar and intrahepatic lipids. Resting energy expenditure was similar between the groups, but respiratory quotient was higher and total energy expenditure was lower in LCHAD-deficient patients compared with controls. High-molecular-weight (HMW) adiponectin levels were lower and plasma long-chain acylcarnitines were higher among LCHAD-deficient patients. Fasting and post-OGTT levels of glucose, insulin, and ghrelin, along with estimates of insulin sensitivity, were the same between the groups. Despite decreased capacity for FAO, lower total energy expenditure and plasma HMW adiponectin, and increased plasma acylcarnitines, LCHAD-deficient patients exhibited normal glucose tolerance. These data suggest that inhibition of the FAO pathway in humans is not sufficient to induce insulin resistance.
American journal of physiology. Endocrinology and metabolism.Am J Physiol Endocrinol Metab.2013 Nov 15;305(10):E1299-308. doi: 10.1152/ajpendo.00225.2013. Epub 2013 Sep 24.
The development of insulin resistance has been associated with impaired mitochondrial fatty acid oxidation (FAO), but the exact relationship between FAO capacity and glucose metabolism continues to be debated. To address this controversy, patients with long-chain 3-hydroxy acyl-CoA dehydrogenase (LC
PMID 24064340

Japanese Journal

早期治療できた急性妊娠脂肪肝の1例

佐藤晴香,中山摂子,檜垣博 [他]
東京産科婦人科学会会誌 60(3), 427-432, 2011-09
NAID 40019362445

Post-mortem analysis for two prevalent β-oxidation mutations in sudden infant death

YANG ZI,LANTZ PATRICK E.,IBDAH JAMAL A.
Pediatrics international : official journal of the Japan Pediatric Society 49(6), 883-887, 2007-12-01
NAID 10024151700

Lack of common mutation in the alfa-subunit of the mitochondrial trifunctional protein and the polymorphism of CYP2E1 in three Japanese women with acute fatty liver of pregnancy/HELLP syndrome

FUKUSHIMA Koji,UENO Yoshiyuki,INOUE Jun,KANNO Noriatsu,NAGASAKI Futoshi,MIKAMI Emiko,MORITOKI Yuki,KONDO Yasuteru,SHIMOSEGAWA Tooru
Hepatology research : the official journal of the Japan Society of Hepatology 30(4), 226-231, 2004-12-01
NAID 10018025984

Related Pictures

Christopher LCHAD What is Mitochondrial Trifunctional blood in a patient with LCHAD deficieny If MCADD is not treated, what problems months old infant with LCHAD deficiency File:LCHAD deficiency.jpg Figure 1: Schematic for the investigation Definition of « LCHAD deficiency »