Format

Send to:

Choose Destination

Very long chain acyl-CoA dehydrogenase deficiency(VLCAD)

MedGen UID:
854382
Concept ID:
C3887523
Disease or Syndrome
Synonyms: VLCAD; VLCAD deficiency
SNOMED CT: Very long chain acyl-coenzyme A dehydrogenase deficiency (237997005); Very long chain acyl-CoA dehydrogenase deficiency (237997005); VLCAD - Very long chain acyl-CoA dehydrogenase deficiency (237997005)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM
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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): ACADVL (17p13.1)
 
Monarch Initiative: MONDO:0008723
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 multiorgan 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 provoked by exercise, 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 (ACADMD; 201450), short-chain acyl-CoA dehydrogenase deficiency (ACADSD; 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 MedlinePlus Genetics
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).\n\nSigns 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 usually involve muscle pain and the breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown.\n\nIn both children and adults, problems related to VLCAD deficiency can be triggered by periods of fasting, illness, and exercise. In affected children, 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://medlineplus.gov/genetics/condition/very-long-chain-acyl-coa-dehydrogenase-deficiency

Clinical features

From HPO
Sudden cardiac death
MedGen UID:
38841
Concept ID:
C0085298
Pathologic Function
An unexpected natural death from a cardiac cause within a short time period from the onset of symptoms.
Exercise-induced myalgia
MedGen UID:
340638
Concept ID:
C1850830
Sign or Symptom
The occurrence of an unusually high amount of muscle pain following exercise.
Exercise-induced myoglobinuria
MedGen UID:
337172
Concept ID:
C1845155
Finding
Presence of myoglobin in the urine following exercise.
Dicarboxylic aciduria
MedGen UID:
343550
Concept ID:
C1856432
Finding
An increased concentration of dicarboxylic acid in the urine.
Hypertrophic cardiomyopathy
MedGen UID:
2881
Concept ID:
C0007194
Disease or Syndrome
A condition in which the myocardium is hypertrophied without an obvious cause. The hypertrophy is generally asymmetric and may be associated with obstruction of the ventricular outflow tract.
Sudden cardiac death
MedGen UID:
38841
Concept ID:
C0085298
Pathologic Function
An unexpected natural death from a cardiac cause within a short time period from the onset of symptoms.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size 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
Steatosis is a term used to denote lipid accumulation within hepatocytes.
Lethargy
MedGen UID:
7310
Concept ID:
C0023380
Sign or Symptom
A state of disinterestedness, listlessness, and indifference, resulting in difficulty performing simple tasks or concentrating.
Muscular hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
A condition of decreased tone of the skeletal muscles and diminished resistance to passive stretching.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
A reduction in the strength of one or more 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.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Exercise-induced rhabdomyolysis
MedGen UID:
867168
Concept ID:
C4021526
Finding
Rhabdomyolysis induced by exercise.
Tachypnea
MedGen UID:
66669
Concept ID:
C0231835
Finding
Very rapid breathing.
Elevated serum creatine phosphokinase
MedGen UID:
69128
Concept ID:
C0241005
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.
Decreased plasma carnitine
MedGen UID:
222973
Concept ID:
C1142132
Finding
A decreased concentration of carnitine in the blood.
Exercise-induced myoglobinuria
MedGen UID:
337172
Concept ID:
C1845155
Finding
Presence of myoglobin in the urine following exercise.
Dicarboxylic aciduria
MedGen UID:
343550
Concept ID:
C1856432
Finding
An increased concentration of dicarboxylic acid in the urine.
Nonketotic hypoglycemia
MedGen UID:
400730
Concept ID:
C1865292
Finding
Decreased plasma carnitine
MedGen UID:
222973
Concept ID:
C1142132
Finding
A decreased concentration of carnitine in the blood.

Recent clinical studies

Etiology

Van Calcar SC, Sowa M, Rohr F, Beazer J, Setlock T, Weihe TU, Pendyal S, Wallace LS, Hansen JG, Stembridge A, Splett P, Singh RH
Mol Genet Metab 2020 Sep - Oct;131(1-2):23-37. Epub 2020 Oct 6 doi: 10.1016/j.ymgme.2020.10.001. PMID: 33093005
Alhashem A, Mohamed S, Abdelraheem M, AlGufaydi B, Al-Aqeel A
Saudi Med J 2020 Jun;41(6):590-596. doi: 10.15537/smj.2020.6.25131. PMID: 32518924Free PMC Article
Bleeker JC, Kok IL, Ferdinandusse S, van der Pol WL, Cuppen I, Bosch AM, Langeveld M, Derks TGJ, Williams M, de Vries M, Mulder MF, Gozalbo ER, de Sain-van der Velden MGM, Rennings AJ, Schielen PJCI, Dekkers E, Houtkooper RH, Waterham HR, Pras-Raves ML, Wanders RJA, van Hasselt PM, Schoenmakers M, Wijburg FA, Visser G
J Inherit Metab Dis 2019 May;42(3):414-423. Epub 2019 Apr 8 doi: 10.1002/jimd.12075. PMID: 30761551
Ryder B, Knoll D, Love DR, Shepherd P, Love JM, Reed PW, de Hora M, Webster D, Glamuzina E, Wilson C
J Inherit Metab Dis 2016 May;39(3):409-414. Epub 2016 Jan 7 doi: 10.1007/s10545-015-9911-z. PMID: 26743058
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

Fuseya Y, Sakurai T, Miyahara JI, Sato K, Kaji S, Saito Y, Takahashi M, Nishino I, Fukuda T, Sugie H, Yamashita H
Intern Med 2020 Nov 1;59(21):2729-2732. Epub 2020 Jul 14 doi: 10.2169/internalmedicine.4604-20. PMID: 32669490Free PMC Article
Fatehi F, Okhovat AA, Nilipour Y, Mroczek M, Straub V, Töpf A, Palibrk A, Peric S, Rakocevic Stojanovic V, Najmabadi H, Nafissi S
Eur J Neurol 2020 Nov;27(11):2257-2266. Epub 2020 Jul 24 doi: 10.1111/ene.14402. PMID: 32558070Free PMC Article
Bleeker JC, Kok IL, Ferdinandusse S, van der Pol WL, Cuppen I, Bosch AM, Langeveld M, Derks TGJ, Williams M, de Vries M, Mulder MF, Gozalbo ER, de Sain-van der Velden MGM, Rennings AJ, Schielen PJCI, Dekkers E, Houtkooper RH, Waterham HR, Pras-Raves ML, Wanders RJA, van Hasselt PM, Schoenmakers M, Wijburg FA, Visser G
J Inherit Metab Dis 2019 May;42(3):414-423. Epub 2019 Apr 8 doi: 10.1002/jimd.12075. PMID: 30761551
Bleeker JC, Kok IL, Ferdinandusse S, de Vries M, Derks TGJ, Mulder MF, Williams M, Gozalbo ER, Bosch AM, van den Hurk DT, de Sain-van der Velden MGM, Waterham HR, Wijburg FA, Visser G
J Inherit Metab Dis 2019 Jan;42(1):159-168. doi: 10.1002/jimd.12037. PMID: 30740737
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

Shiraishi H, Yamada K, Egawa K, Ishige M, Ochi F, Watanabe A, Kawakami S, Kuzume K, Watanabe K, Sameshima K, Nakamagoe K, Tamaoka A, Asahina N, Yokoshiki S, Kobayashi K, Miyakoshi T, Oba K, Isoe T, Hayashi H, Yamaguchi S, Sato N
Brain Dev 2021 Feb;43(2):214-219. Epub 2020 Aug 11 doi: 10.1016/j.braindev.2020.07.019. PMID: 32798077
Alhashem A, Mohamed S, Abdelraheem M, AlGufaydi B, Al-Aqeel A
Saudi Med J 2020 Jun;41(6):590-596. doi: 10.15537/smj.2020.6.25131. PMID: 32518924Free PMC Article
Bleeker JC, Visser G, Clarke K, Ferdinandusse S, de Haan FH, Houtkooper RH, IJlst L, Kok IL, Langeveld M, van der Pol WL, de Sain-van der Velden MGM, Sibeijn-Kuiper A, Takken T, Wanders RJA, van Weeghel M, Wijburg FA, van der Woude LH, Wüst RCI, Cox PJ, Jeneson JAL
J Inherit Metab Dis 2020 Jul;43(4):787-799. Epub 2020 Feb 5 doi: 10.1002/jimd.12217. PMID: 31955429Free PMC Article
Bleeker JC, Kok IL, Ferdinandusse S, de Vries M, Derks TGJ, Mulder MF, Williams M, Gozalbo ER, Bosch AM, van den Hurk DT, de Sain-van der Velden MGM, Waterham HR, Wijburg FA, Visser G
J Inherit Metab Dis 2019 Jan;42(1):159-168. doi: 10.1002/jimd.12037. PMID: 30740737
Yamada K, Taketani T
J Hum Genet 2019 Feb;64(2):73-85. Epub 2018 Nov 6 doi: 10.1038/s10038-018-0527-7. PMID: 30401918

Prognosis

Bleeker JC, Kok IL, Ferdinandusse S, de Vries M, Derks TGJ, Mulder MF, Williams M, Gozalbo ER, Bosch AM, van den Hurk DT, de Sain-van der Velden MGM, Waterham HR, Wijburg FA, Visser G
J Inherit Metab Dis 2019 Jan;42(1):159-168. doi: 10.1002/jimd.12037. PMID: 30740737
Yamada K, Taketani T
J Hum Genet 2019 Feb;64(2):73-85. Epub 2018 Nov 6 doi: 10.1038/s10038-018-0527-7. PMID: 30401918
Hisahara S, Matsushita T, Furuyama H, Tajima G, Shigematsu Y, Imai T, Shimohama S
Tohoku J Exp Med 2015 Apr;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

Clinical prediction guides

Alhashem A, Mohamed S, Abdelraheem M, AlGufaydi B, Al-Aqeel A
Saudi Med J 2020 Jun;41(6):590-596. doi: 10.15537/smj.2020.6.25131. PMID: 32518924Free PMC Article
Alatibi KI, Wehbe Z, Spiekerkoetter U, Tucci S
FEBS J 2020 Aug;287(16):3511-3525. Epub 2020 Feb 6 doi: 10.1111/febs.15221. PMID: 31971349
Bleeker JC, Kok IL, Ferdinandusse S, de Vries M, Derks TGJ, Mulder MF, Williams M, Gozalbo ER, Bosch AM, van den Hurk DT, de Sain-van der Velden MGM, Waterham HR, Wijburg FA, Visser G
J Inherit Metab Dis 2019 Jan;42(1):159-168. doi: 10.1002/jimd.12037. PMID: 30740737
Hesse J, Braun C, Behringer S, Matysiak U, Spiekerkoetter U, Tucci S
J Inherit Metab Dis 2018 Nov;41(6):1169-1178. Epub 2018 Sep 7 doi: 10.1007/s10545-018-0245-5. PMID: 30194637
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

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center