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Very long chain acyl-CoA dehydrogenase deficiency(VLCAD)

MedGen UID:
87459
Concept ID:
C0342784
Disease or Syndrome
Synonyms: Long chain acyl-CoA dehydrogenase deficiency; VLCAD; VLCAD deficiency
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
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 (location): ACADVL (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]
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.  https://ghr.nlm.nih.gov/condition/very-long-chain-acyl-coa-dehydrogenase-deficiency

Clinical features

Exercise-induced myalgia
MedGen UID:
340638
Concept ID:
C1850830
Sign or Symptom
The occurrence of an unusually high amount of muscle pain following exercise.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Sign or Symptom
Enlargement of the liver.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Hepatocellular necrosis
MedGen UID:
343247
Concept ID:
C1855038
Disease or Syndrome
Hepatic steatosis
MedGen UID:
398225
Concept ID:
C2711227
Disease or Syndrome
The presence of steatosis in the liver.
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
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 weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Muscle stiffness
MedGen UID:
113151
Concept ID:
C0221170
Sign or Symptom
A condition in which muscles cannot be moved quickly without accompanying pain or spasm.
Exercise-induced rhabdomyolysis
MedGen UID:
867168
Concept ID:
C4021526
Finding
Rhabdomyolysis induced by exercise.
Creatine phosphokinase, elevated serum
MedGen UID:
69128
Concept ID:
C0241005
Finding
The caveolinopathies, a group of muscle diseases, can be classified into five phenotypes, which can be seen in different members of the same family: Limb-girdle muscular dystrophy 1C (LGMD1C), characterized by onset usually in the first decade, mild-to-moderate proximal muscle weakness, calf hypertrophy, positive Gower sign, and variable muscle cramps after exercise . Isolated hyperCKemia (i.e., elevated serum concentration of creatine kinase (CK) in the absence of signs of muscle disease) (HCK). Rippling muscle disease (RMD), characterized by signs of increased muscle irritability, such as percussion-induced rapid contraction (PIRC), percussion-induced muscle mounding (PIMM), and/or electrically silent muscle contractions (rippling muscle). Distal myopathy (DM), observed in one individual only Hypertrophic cardiomyopathy (HCM), without skeletal muscle manifestations.
Decreased plasma carnitine
MedGen UID:
222973
Concept ID:
C1142132
Finding
A decreased concentration of carnitine in the blood.
Dicarboxylic aciduria
MedGen UID:
343550
Concept ID:
C1856432
Finding
An increased concentration of dicarboxylic acid in the urine.

Term Hierarchy

Follow this link to review classifications for Very long chain acyl-CoA dehydrogenase deficiency in Orphanet.

Recent clinical studies

Etiology

Ko JM, Seo J, Choi M, Song J, Lee KA, Shin CH
Ann Clin Lab Sci 2016 Winter;46(1):97-101. PMID: 26927351
Diekman EF, Visser G, Schmitz JP, Nievelstein RA, de Sain-van der Velden M, Wardrop M, Van der Pol WL, Houten SM, van Riel NA, Takken T, Jeneson JA
PLoS One 2016 Feb 16;11(2):e0147818. doi: 10.1371/journal.pone.0147818. PMID: 26881790Free PMC Article
Takahashi Y, Sano R, Nakajima T, Kominato Y, Kubo R, Takahashi K, Ohshima N, Hirano T, Kobayashi S, Shimada T, Tokue H, Awata S, Hirasawa S, Ishige T
Forensic Sci Int 2014 Nov;244:e34-7. Epub 2014 Sep 6 doi: 10.1016/j.forsciint.2014.08.031. PMID: 25242572
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. 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. PMID: 24503138

Diagnosis

Ko JM, Seo J, Choi M, Song J, Lee KA, Shin CH
Ann Clin Lab Sci 2016 Winter;46(1):97-101. PMID: 26927351
Stępień KM, Roberts M, Hendriksz CJ
Dev Period Med 2015 Oct-Dec;19(4):450-3. PMID: 26982752
Brown A, Crowe L, Andresen BS, Anderson V, Boneh A
Mol Genet Metab 2014 Dec;113(4):278-82. Epub 2014 Oct 12 doi: 10.1016/j.ymgme.2014.10.005. PMID: 25456746
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. 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. PMID: 24503138

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. 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. PMID: 19157942Free PMC Article
Voermans NC, Poels PJ, Kluijtmans LA, van Engelen BG
Neuromuscul Disord 2005 Dec;15(12):844-6. Epub 2005 Nov 8 doi: 10.1016/j.nmd.2005.09.003. PMID: 16288870
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

Prognosis

Hisahara S, Matsushita T, Furuyama H, Tajima G, Shigematsu Y, Imai T, Shimohama S
Tohoku J Exp Med 2015;235(4):305-10. doi: 10.1620/tjem.235.305. PMID: 25843429
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. 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. 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. PMID: 21333574
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. PMID: 20060901Free PMC Article

Clinical prediction guides

Diekman EF, Visser G, Schmitz JP, Nievelstein RA, de Sain-van der Velden M, Wardrop M, Van der Pol WL, Houten SM, van Riel NA, Takken T, Jeneson JA
PLoS One 2016 Feb 16;11(2):e0147818. doi: 10.1371/journal.pone.0147818. PMID: 26881790Free PMC Article
Brown A, Crowe L, Andresen BS, Anderson V, Boneh A
Mol Genet Metab 2014 Dec;113(4):278-82. Epub 2014 Oct 12 doi: 10.1016/j.ymgme.2014.10.005. PMID: 25456746
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. 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. 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. PMID: 21333574

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. 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. PMID: 19157942Free PMC Article

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