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Very long chain acyl-CoA dehydrogenase deficiency(VLCAD)

MedGen UID:
87459
Concept ID:
C0342784
Disease or Syndrome
Synonyms: ACYL-CoA DEHYDROGENASE, LONG-CHAIN, DEFICIENCY OF; ACYL-CoA DEHYDROGENASE, VERY LONG-CHAIN, DEFICIENCY OF; Long chain acyl-CoA dehydrogenase deficiency; Very Long Chain Acyl-Coenzyme A Dehydrogenase Deficiency; VLCAD; VLCAD deficiency
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
SNOMED CT: Pearson syndrome (237985009); Very long chain acyl-coenzyme A dehydrogenase deficiency (237997005); Pearson's syndrome (237985009); Very long chain acyl-CoA dehydrogenase deficiency (237997005); VLCAD - Very long chain acyl-CoA dehydrogenase deficiency (237997005)
 
Gene: ACADVL
Cytogenetic location: 17p13.1
OMIM®: 201475
Orphanet: ORPHA26793

Disease characteristics

Deficiency of very long-chain acyl-CoA dehydrogenase (VLCAD), which catalyzes the initial step of mitochondrial β-oxidation of long-chain fatty acids with a chain length of 14 to 20 carbons, is associated with three phenotypes. The severe early-onset cardiac and multi-organ failure form typically presents in the first months of life with hypertrophic or dilated cardiomyopathy, pericardial effusion, and arrhythmias, as well as hypotonia, hepatomegaly, and intermittent hypoglycemia. The hepatic or hypoketotic hypoglycemic form typically presents during early childhood with hypoketotic hypoglycemia and hepatomegaly, but without cardiomyopathy. The later-onset episodic myopathic form presents with intermittent rhabdomyolysis, muscle cramps and/or pain, and/or exercise intolerance. Hypoglycemia typically is not present at the time of symptoms. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Nancy D Leslie  |  C Alexander Valencia  |  Arnold W Strauss, et. al.   view full author information

Additional descriptions

From OMIM
Inborn errors of mitochondrial fatty acid beta-oxidation include medium-chain acyl-CoA dehydrogenase deficiency (201450), short-chain acyl-CoA dehydrogenase deficiency (201470), and very long-chain acyl-CoA dehydrogenase deficiency. VLCAD deficiency can be classified clinically into 3 forms: a severe early-onset form with high incidence of cardiomyopathy and high mortality; an intermediate form with childhood onset, usually with hypoketotic hypoglycemia and more favorable outcome; and an adult-onset, myopathic form with isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria after exercise or fasting (Andresen et al., 1999). Patients reported with long-chain acyl-CoA dehydrogenase (LCAD) deficiency before VLCAD deficiency was defined were later found to have VLCAD deficiency (Strauss et al., 1995; Roe and Ding, 2001).  http://www.omim.org/entry/201475
From GHR
Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting). Signs and symptoms of VLCAD deficiency typically appear during infancy or early childhood and can include low blood sugar (hypoglycemia), lack of energy (lethargy), and muscle weakness. Affected individuals are also at risk for serious complications such as liver abnormalities and life-threatening heart problems. When symptoms begin in adolescence or adulthood, they tend to be milder and usually do not involve the heart. Problems related to VLCAD deficiency can be triggered by periods of fasting, illness, and exercise. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.  http://ghr.nlm.nih.gov/condition/very-long-chain-acyl-coa-dehydrogenase-deficiency

Clinical features

Dicarboxylic aciduria
MedGen UID:
343550
Concept ID:
C1856432
Finding
Exercise-induced myoglobinuria
MedGen UID:
348016
Concept ID:
C1860069
Finding
Lethargy
MedGen UID:
504769
Concept ID:
CN001149
Finding
A state of disinterestedness, listlessness, and indifference, resulting in difficulty performing simple tasks or concentrating.
Vomiting
MedGen UID:
776588
Concept ID:
C2712332
Finding
Hepatic steatosis
MedGen UID:
427871
Concept ID:
CN001278
Finding
The presence of steatosis in the liver.
Hepatocellular necrosis
MedGen UID:
504830
Concept ID:
CN001285
Finding
Hepatomegaly
MedGen UID:
505165
Concept ID:
CN002031
Finding
Abnormally increased size of the liver.
Sudden cardiac death
MedGen UID:
369872
Concept ID:
C1968862
Finding
Hypertrophic cardiomyopathy
MedGen UID:
504884
Concept ID:
CN001492
Finding
Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality.
Dicarboxylic aciduria
MedGen UID:
343550
Concept ID:
C1856432
Finding
Exercise-induced myoglobinuria
MedGen UID:
348016
Concept ID:
C1860069
Finding
Nonketotic hypoglycemia
MedGen UID:
400730
Concept ID:
C1865292
Finding
Decreased plasma carnitine
MedGen UID:
760078
Concept ID:
CN002921
Finding
A decreased concentration of carnitine in the blood.
Elevated serum creatine phosphokinase
MedGen UID:
505493
Concept ID:
CN002923
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase, CPK; EC 2.7.3.2) in the blood. CPK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Tachypnea
MedGen UID:
66669
Concept ID:
C0231835
Sign or Symptom
Increased RESPIRATORY RATE.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
A vague complaint of debility, fatigue, or exhaustion attributable to weakness of various muscles. The weakness can be characterized as subacute or chronic, often progressive, and is a manifestation of many muscle and neuromuscular diseases. (From Wyngaarden et al., Cecil Textbook of Medicine, 19th ed, p2251)
Muscular hypotonia
MedGen UID:
504768
Concept ID:
CN001147
Finding
Muscular hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. Hypotonia is characterized by a diminished resistance to passive stretching.
Muscle stiffness
MedGen UID:
505558
Concept ID:
CN003206
Finding
A condition in which muscles cannot be moved quickly without accompanying pain or spasm.
Exercise-induced myalgia
MedGen UID:
505583
Concept ID:
CN003377
Finding
The occurrence of an unusually high amount of muscle pain following exercise.
Exercise-induced rhabdomyolysis
MedGen UID:
429271
Concept ID:
CN007947
Finding
Rhabdomyolysis induced by exercise.

Recent clinical studies

Etiology

Zhang RN, Li YF, Qiu WJ, Ye J, Han LS, Zhang HW, Lin N, Gu XF
World J Pediatr 2014 May;10(2):119-25. Epub 2014 May 7 doi: 10.1007/s12519-014-0480-2. [Epub ahead of print] PMID: 24801231
Merritt JL 2nd, Vedal S, Abdenur JE, Au SM, Barshop BA, Feuchtbaum L, Harding CO, Hermerath C, Lorey F, Sesser DE, Thompson JD, Yu A
Mol Genet Metab 2014 Apr;111(4):484-92. Epub 2014 Jan 23 doi: 10.1016/j.ymgme.2014.01.009. [Epub ahead of print] PMID: 24503138
Sedgwick ER
J Pediatr Nurs 2013 Jul-Aug;28(4):379-82. Epub 2012 Dec 10 doi: 10.1016/j.pedn.2012.11.002. [Epub ahead of print] PMID: 23238219
Siu WK, Mak CM, Siu SL, Siu TS, Pang CY, Lam CW, Kwong NS, Chan AY
Diagn Mol Pathol 2012 Sep;21(3):184-7. doi: 10.1097/PDM.0b013e31825554d0. PMID: 22847164
Coughlin CR 2nd, Ficicioglu C
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S129-31. Epub 2010 Jan 27 doi: 10.1007/s10545-009-9041-6. [Epub ahead of print] PMID: 20107901

Diagnosis

Zhang RN, Li YF, Qiu WJ, Ye J, Han LS, Zhang HW, Lin N, Gu XF
World J Pediatr 2014 May;10(2):119-25. Epub 2014 May 7 doi: 10.1007/s12519-014-0480-2. [Epub ahead of print] PMID: 24801231
Merritt JL 2nd, Vedal S, Abdenur JE, Au SM, Barshop BA, Feuchtbaum L, Harding CO, Hermerath C, Lorey F, Sesser DE, Thompson JD, Yu A
Mol Genet Metab 2014 Apr;111(4):484-92. Epub 2014 Jan 23 doi: 10.1016/j.ymgme.2014.01.009. [Epub ahead of print] PMID: 24503138
Schiff M, Mohsen AW, Karunanidhi A, McCracken E, Yeasted R, Vockley J
Mol Genet Metab 2013 May;109(1):21-7. Epub 2013 Feb 13 doi: 10.1016/j.ymgme.2013.02.002. [Epub ahead of print] PMID: 23480858Free PMC Article
Sedgwick ER
J Pediatr Nurs 2013 Jul-Aug;28(4):379-82. Epub 2012 Dec 10 doi: 10.1016/j.pedn.2012.11.002. [Epub ahead of print] PMID: 23238219
Siu WK, Mak CM, Siu SL, Siu TS, Pang CY, Lam CW, Kwong NS, Chan AY
Diagn Mol Pathol 2012 Sep;21(3):184-7. doi: 10.1097/PDM.0b013e31825554d0. PMID: 22847164

Therapy

Ficicioglu C, Hussa C
J Inherit Metab Dis 2009 Dec;32 Suppl 1:S187-90. Epub 2009 Apr 4 doi: 10.1007/s10545-009-1143-7. [Epub ahead of print] PMID: 19333779
Arnold GL, Van Hove J, Freedenberg D, Strauss A, Longo N, Burton B, Garganta C, Ficicioglu C, Cederbaum S, Harding C, Boles RG, Matern D, Chakraborty P, Feigenbaum A
Mol Genet Metab 2009 Mar;96(3):85-90. Epub 2009 Jan 20 doi: 10.1016/j.ymgme.2008.09.008. [Epub ahead of print] PMID: 19157942Free PMC Article
Boles RG
J Inherit Metab Dis 2002 Aug;25(4):315-6. PMID: 12227461
Doi T, Abo W, Tateno M, Hayashi K, Hori T, Nakada T, Fukao T, Takahashi Y, Terada N
Eur J Pediatr 2000 Dec;159(12):908-11. PMID: 11131350
Costa CG, Dorland L, de Almeida IT, Jakobs C, Duran M, Poll-The BT
J Inherit Metab Dis 1998 Jun;21(4):391-9. PMID: 9700596

Prognosis

Zhang RN, Li YF, Qiu WJ, Ye J, Han LS, Zhang HW, Lin N, Gu XF
World J Pediatr 2014 May;10(2):119-25. Epub 2014 May 7 doi: 10.1007/s12519-014-0480-2. [Epub ahead of print] PMID: 24801231
Merritt JL 2nd, Vedal S, Abdenur JE, Au SM, Barshop BA, Feuchtbaum L, Harding CO, Hermerath C, Lorey F, Sesser DE, Thompson JD, Yu A
Mol Genet Metab 2014 Apr;111(4):484-92. Epub 2014 Jan 23 doi: 10.1016/j.ymgme.2014.01.009. [Epub ahead of print] PMID: 24503138
Sedgwick ER
J Pediatr Nurs 2013 Jul-Aug;28(4):379-82. Epub 2012 Dec 10 doi: 10.1016/j.pedn.2012.11.002. [Epub ahead of print] PMID: 23238219
Siu WK, Mak CM, Siu SL, Siu TS, Pang CY, Lam CW, Kwong NS, Chan AY
Diagn Mol Pathol 2012 Sep;21(3):184-7. doi: 10.1097/PDM.0b013e31825554d0. PMID: 22847164
Vellekoop P, Diekman EF, van Tuijl I, de Vries MM, van Hasselt PM, Visser G
Mol Genet Metab 2011 May;103(1):96-7. Epub 2011 Jan 27 doi: 10.1016/j.ymgme.2011.01.010. [Epub ahead of print] PMID: 21333574

Clinical prediction guides

Zhang RN, Li YF, Qiu WJ, Ye J, Han LS, Zhang HW, Lin N, Gu XF
World J Pediatr 2014 May;10(2):119-25. Epub 2014 May 7 doi: 10.1007/s12519-014-0480-2. [Epub ahead of print] PMID: 24801231
Merritt JL 2nd, Vedal S, Abdenur JE, Au SM, Barshop BA, Feuchtbaum L, Harding CO, Hermerath C, Lorey F, Sesser DE, Thompson JD, Yu A
Mol Genet Metab 2014 Apr;111(4):484-92. Epub 2014 Jan 23 doi: 10.1016/j.ymgme.2014.01.009. [Epub ahead of print] PMID: 24503138
Vellekoop P, Diekman EF, van Tuijl I, de Vries MM, van Hasselt PM, Visser G
Mol Genet Metab 2011 May;103(1):96-7. Epub 2011 Jan 27 doi: 10.1016/j.ymgme.2011.01.010. [Epub ahead of print] PMID: 21333574
Coughlin CR 2nd, Ficicioglu C
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S129-31. Epub 2010 Jan 27 doi: 10.1007/s10545-009-9041-6. [Epub ahead of print] PMID: 20107901
Gobin-Limballe S, McAndrew RP, Djouadi F, Kim JJ, Bastin J
Biochim Biophys Acta 2010 May;1802(5):478-84. Epub 2010 Jan 12 doi: 10.1016/j.bbadis.2010.01.001. [Epub ahead of print] PMID: 20060901Free PMC Article

Recent systematic reviews

Lindner M, Hoffmann GF, Matern D
J Inherit Metab Dis 2010 Oct;33(5):521-6. Epub 2010 Apr 7 doi: 10.1007/s10545-010-9076-8. [Epub ahead of print] PMID: 20373143
Arnold GL, Van Hove J, Freedenberg D, Strauss A, Longo N, Burton B, Garganta C, Ficicioglu C, Cederbaum S, Harding C, Boles RG, Matern D, Chakraborty P, Feigenbaum A
Mol Genet Metab 2009 Mar;96(3):85-90. Epub 2009 Jan 20 doi: 10.1016/j.ymgme.2008.09.008. [Epub ahead of print] PMID: 19157942Free PMC Article

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