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Deficiency of butyryl-CoA dehydrogenase(ACADSD)

MedGen UID:
90998
Concept ID:
C0342783
Disease or Syndrome
Synonyms: ACADSD; ACYL-CoA DEHYDROGENASE, SHORT-CHAIN, DEFICIENCY OF; Lipid-storage myopathy secondary to short chain acyl CoA dehydrogenase deficiency; SCAD DEFICIENCY, MILD; Short Chain Acyl-CoA Dehydrogenase Deficiency
SNOMED CT: Deficiency of unsaturated acyl-CoA reductase (124166007); Deficiency of butyryl dehydrogenase (124166007); Deficiency of butyryl-CoA dehydrogenase (124166007); Short chain acyl-CoA dehydrogenase deficiency (787412002); Short chain acyl-coenzyme A dehydrogenase deficiency (787412002); SCAD - short chain acyl-CoA dehydrogenase deficiency (787412002); ACADS - short chain acyl-coenzyme A dehydrogenase deficiency (787412002); Butyryl-CoA dehydrogenase deficiency (124166007)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: 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 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): ACADS (12q24.31)
 
Monarch Initiative: MONDO:0008722
OMIM®: 201470
Orphanet: ORPHA26792

Disease characteristics

Excerpted from the GeneReview: Short-Chain Acyl-CoA Dehydrogenase Deficiency
Most infants with short-chain acyl-CoA dehydrogenase deficiency (SCADD) identified through newborn screening programs have remained well, and asymptomatic relatives who meet diagnostic criteria are reported. Thus, SCADD is now viewed as a biochemical phenotype rather than a disease. A broad range of clinical findings was originally reported in those with confirmed SCADD, including severe dysmorphic facial features, feeding difficulties / failure to thrive, metabolic acidosis, ketotic hypoglycemia, lethargy, developmental delay, seizures, hypotonia, dystonia, and myopathy. However, individuals with no symptoms were also reported. In a large series of affected individuals detected on metabolic evaluation for developmental delay, 20% had failure to thrive, feeding difficulties, and hypotonia; 22% had seizures; and 30% had hypotonia without seizures. In contrast, the majority of infants with SCADD have been detected by expanded newborn screening, and the great majority of these infants remain asymptomatic. As with other fatty acid oxidation deficiencies, characteristic biochemical findings of SCADD may be absent except during times of physiologic stress such as fasting and illness. A diagnosis of SCADD based on clinical findings should not preclude additional testing to look for other causes. [from GeneReviews]
Authors:
Lynne Wolfe  |  Reena Jethva  |  Devin Oglesbee, et. al.   view full author information

Additional descriptions

From OMIM
SCAD deficiency is an autosomal recessive metabolic disorder of fatty acid beta-oxidation. Clinical features are variable: a severe form of the disorder can cause infantile onset of acidosis and neurologic impairment, whereas some patients develop only myopathy. With the advent of screening for inborn errors of metabolism, patients with putative pathogenic mutations but who remain asymptomatic have also been identified (summary by Shirao et al., 2010).  http://www.omim.org/entry/201470
From MedlinePlus Genetics
Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is a condition that prevents the body from converting certain fats into energy, especially during periods without food (fasting).

Signs and symptoms of SCAD deficiency may appear during infancy or early childhood and can include vomiting, low blood glucose (hypoglycemia), a lack of energy (lethargy), poor feeding, and failure to gain weight and grow at the expected rate (failure to thrive). Other features of this disorder may include poor muscle tone (hypotonia), seizures, developmental delay, and a small head size (microcephaly).

The symptoms of SCAD deficiency may be triggered by fasting or illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe condition 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.

In some people with SCAD deficiency, signs and symptoms do not appear until adulthood. These individuals are more likely to have problems related to muscle weakness and wasting.

The severity of this condition varies widely, even among members of the same family. Some individuals are diagnosed with SCAD deficiency based on laboratory testing but never develop any symptoms of the condition.  https://medlineplus.gov/genetics/condition/short-chain-acyl-coa-dehydrogenase-deficiency

Clinical features

From HPO
Ethylmalonic aciduria
MedGen UID:
355967
Concept ID:
C1865353
Finding
The concentration of ethylmalonic acid in the urine, normalized for urine concentration, is above the upper limit of normal.
Cardiomyopathy
MedGen UID:
209232
Concept ID:
C0878544
Disease or Syndrome
A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Lethargy
MedGen UID:
7310
Concept ID:
C0023380
Sign or Symptom
A state of disinterest, listlessness, and indifference, resulting in difficulty performing simple tasks or concentrating.
Psychotic disorder
MedGen UID:
19568
Concept ID:
C0033975
Mental or Behavioral Dysfunction
A condition characterized by changes in personality and thought patterns, often accompanied by hallucinations and delusional beliefs, is known as psychosis.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Abnormal pyramidal sign
MedGen UID:
68582
Concept ID:
C0234132
Sign or Symptom
Functional neurological abnormalities related to dysfunction of the pyramidal tract.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Abnormal cerebral white matter morphology
MedGen UID:
181756
Concept ID:
C0948163
Pathologic Function
An abnormality of the cerebral white matter.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Myopathy
MedGen UID:
10135
Concept ID:
C0026848
Disease or Syndrome
A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Weakness of facial musculature
MedGen UID:
98103
Concept ID:
C0427055
Disease or Syndrome
Reduced strength of one or more muscles innervated by the facial nerve (the seventh cranial nerve).
Episodic metabolic acidosis
MedGen UID:
349179
Concept ID:
C1859516
Finding
Repeated transient episodes of metabolic acidosis, that is, of the buildup of acid or depletion of base due to accumulation of metabolic acids.
External ophthalmoplegia
MedGen UID:
57662
Concept ID:
C0162292
Disease or Syndrome
Paralysis of the external ocular muscles.
Sutural cataract
MedGen UID:
869308
Concept ID:
C4023734
Disease or Syndrome
A type of congenital cataract in which the opacity follows the anterior or posterior Y suture.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDeficiency of butyryl-CoA dehydrogenase
Follow this link to review classifications for Deficiency of butyryl-CoA dehydrogenase in Orphanet.

Professional guidelines

PubMed

Lin Y, Zhang W, Chen D, Lin C, Zheng Z, Fu Q, Li M, Peng W
Clin Chim Acta 2020 Nov;510:285-290. Epub 2020 Jul 22 doi: 10.1016/j.cca.2020.07.038. PMID: 32710939
Lin Y, Zheng Q, Zheng T, Zheng Z, Lin W, Fu Q
Clin Chim Acta 2019 Jul;494:106-111. Epub 2019 Mar 21 doi: 10.1016/j.cca.2019.03.1622. PMID: 30904546
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

Curated

American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Elevated C4 Acylcarnitine, Short-Chain Acyl-CoA Dehydrogenase (SCAD) Deficiency, 2022

Recent clinical studies

Etiology

Lisyová J, Chandoga J, Jungová P, Repiský M, Knapková M, Machková M, Dluholucký S, Behúlová D, Šaligová J, Potočňáková Ľ, Lysinová M, Böhmer D
BMC Med Genet 2018 Apr 20;19(1):64. doi: 10.1186/s12881-018-0566-0. PMID: 29678161Free PMC Article
Martens J, Berden G, Bentlage H, Coene KLM, Engelke UF, Wishart D, van Scherpenzeel M, Kluijtmans LAJ, Wevers RA, Oomens J
J Inherit Metab Dis 2018 May;41(3):367-377. Epub 2018 Mar 19 doi: 10.1007/s10545-018-0161-8. PMID: 29556837Free PMC Article
Kiykim E, Zeybek CA, Zubarioglu T, Cansever S, Yalcinkaya C, Soyucen E, Aydin A
Autism Res 2016 Feb;9(2):217-23. Epub 2015 Jun 7 doi: 10.1002/aur.1507. PMID: 26055667
Lanthaler B, Wieser S, Deutschmann A, Schossig A, Fauth C, Zschocke J, Witsch-Baumgartner M
Gene 2014 Oct 15;550(1):136-40. Epub 2014 Aug 8 doi: 10.1016/j.gene.2014.08.016. PMID: 25111118
van Maldegem BT, Duran M, Wanders RJ, Waterham HR, Wijburg FA
Pediatr Res 2010 Mar;67(3):304-8. doi: 10.1203/PDR.0b013e3181cbd57b. PMID: 19952864

Diagnosis

Martens J, Berden G, Bentlage H, Coene KLM, Engelke UF, Wishart D, van Scherpenzeel M, Kluijtmans LAJ, Wevers RA, Oomens J
J Inherit Metab Dis 2018 May;41(3):367-377. Epub 2018 Mar 19 doi: 10.1007/s10545-018-0161-8. PMID: 29556837Free PMC Article
Nochi Z, Olsen RKJ, Gregersen N
J Inherit Metab Dis 2017 Sep;40(5):641-655. Epub 2017 May 17 doi: 10.1007/s10545-017-0047-1. PMID: 28516284
Kiykim E, Zeybek CA, Zubarioglu T, Cansever S, Yalcinkaya C, Soyucen E, Aydin A
Autism Res 2016 Feb;9(2):217-23. Epub 2015 Jun 7 doi: 10.1002/aur.1507. PMID: 26055667
Gallant NM, Leydiker K, Tang H, Feuchtbaum L, Lorey F, Puckett R, Deignan JL, Neidich J, Dorrani N, Chang E, Barshop BA, Cederbaum SD, Abdenur JE, Wang RY
Mol Genet Metab 2012 May;106(1):55-61. Epub 2012 Feb 9 doi: 10.1016/j.ymgme.2012.02.007. PMID: 22424739
van Maldegem BT, Wanders RJ, Wijburg FA
J Inherit Metab Dis 2010 Oct;33(5):507-11. Epub 2010 Apr 29 doi: 10.1007/s10545-010-9080-z. PMID: 20429031Free PMC Article

Therapy

Diaz PL, Katz TM, Langleben AC, Rabinovitch BS, Lewis EC
Wound Manag Prev 2021 Oct;67(10):42-47. PMID: 35030093
Suzuki Y, Ito S, Otani Y, Nishikawa A, Eto K, Hara K, Oguni H, Nagata S
Brain Dev 2021 May;43(5):657-660. Epub 2021 Feb 3 doi: 10.1016/j.braindev.2021.01.001. PMID: 33549404
Van Calcar SC, Baker MW, Williams P, Jones SA, Xiong B, Thao MC, Lee S, Yang MK, Rice GM, Rhead W, Vockley J, Hoffman G, Durkin MS
Mol Genet Metab 2013 Sep-Oct;110(1-2):111-5. Epub 2013 Apr 15 doi: 10.1016/j.ymgme.2013.03.021. PMID: 23712021Free PMC Article
van Maldegem BT, Duran M, Wanders RJ, Waterham HR, Wijburg FA
Pediatr Res 2010 Mar;67(3):304-8. doi: 10.1203/PDR.0b013e3181cbd57b. PMID: 19952864
Turpin B, Tobias JD
Paediatr Anaesth 2005 Sep;15(9):771-7. doi: 10.1111/j.1460-9592.2005.01507.x. PMID: 16101709

Prognosis

Wang W, Yang J, Xue J, Mu W, Zhang X, Wu W, Xu M, Gong Y, Liu Y, Zhang Y, Xie X, Gu W, Bai J, Cram DS
BMC Med Genet 2019 Jan 6;20(1):3. doi: 10.1186/s12881-018-0731-5. PMID: 30612563Free PMC Article
Martens J, Berden G, Bentlage H, Coene KLM, Engelke UF, Wishart D, van Scherpenzeel M, Kluijtmans LAJ, Wevers RA, Oomens J
J Inherit Metab Dis 2018 May;41(3):367-377. Epub 2018 Mar 19 doi: 10.1007/s10545-018-0161-8. PMID: 29556837Free PMC Article
Nafisinia M, Menezes MJ, Gold WA, Riley L, Hatch J, Cardinal J, Coman D, Christodoulou J
Mol Genet Metab 2018 Mar;123(3):382-387. Epub 2018 Feb 2 doi: 10.1016/j.ymgme.2018.01.007. PMID: 29398271
Lanthaler B, Wieser S, Deutschmann A, Schossig A, Fauth C, Zschocke J, Witsch-Baumgartner M
Gene 2014 Oct 15;550(1):136-40. Epub 2014 Aug 8 doi: 10.1016/j.gene.2014.08.016. PMID: 25111118
Gallant NM, Leydiker K, Tang H, Feuchtbaum L, Lorey F, Puckett R, Deignan JL, Neidich J, Dorrani N, Chang E, Barshop BA, Cederbaum SD, Abdenur JE, Wang RY
Mol Genet Metab 2012 May;106(1):55-61. Epub 2012 Feb 9 doi: 10.1016/j.ymgme.2012.02.007. PMID: 22424739

Clinical prediction guides

Gong L, Yang N, Zhao J, Yang H, Tang Y, Li L, Kong Y
Zhejiang Da Xue Xue Bao Yi Xue Ban 2022 Jun 25;51(3):278-283. doi: 10.3724/zdxbyxb-2022-0214. PMID: 36207829Free PMC Article
Butovich IA, Wilkerson A, Bhat N, McMahon A, Yuksel S
FASEB J 2019 Sep;33(9):10034-10048. Epub 2019 Jun 17 doi: 10.1096/fj.201900725R. PMID: 31208226Free PMC Article
Wang W, Yang J, Xue J, Mu W, Zhang X, Wu W, Xu M, Gong Y, Liu Y, Zhang Y, Xie X, Gu W, Bai J, Cram DS
BMC Med Genet 2019 Jan 6;20(1):3. doi: 10.1186/s12881-018-0731-5. PMID: 30612563Free PMC Article
Martens J, Berden G, Bentlage H, Coene KLM, Engelke UF, Wishart D, van Scherpenzeel M, Kluijtmans LAJ, Wevers RA, Oomens J
J Inherit Metab Dis 2018 May;41(3):367-377. Epub 2018 Mar 19 doi: 10.1007/s10545-018-0161-8. PMID: 29556837Free PMC Article
van Maldegem BT, Wanders RJ, Wijburg FA
J Inherit Metab Dis 2010 Oct;33(5):507-11. Epub 2010 Apr 29 doi: 10.1007/s10545-010-9080-z. PMID: 20429031Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • ACMG ACT, 2022
      American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Elevated C4 Acylcarnitine, Short-Chain Acyl-CoA Dehydrogenase (SCAD) Deficiency, 2022

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