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Deficiency of 3-hydroxyacyl-CoA dehydrogenase(M/SCHAD)

MedGen UID:
266222
Concept ID:
C1291230
Disease or Syndrome
Synonyms: 3-alpha hydroxyacyl-CoA dehydrogenase deficiency; 3-hydroxyacyl-CoA dehydrogenase deficiency; 3-Hydroxyacyl-Coenzyme A Dehydrogenase Deficiency; 3-hydroxylacyl-CoA dehydrogenase deficiency; M/SCHAD; Medium and short chain 3-hydroxyacyl-CoA dehydrogenase deficiency
SNOMED CT: Deficiency of beta-keto-reductase (124122005); Deficiency of beta-hydroxyacyl dehydrogenase (124122005); Deficiency of 3-hydroxyacyl-CoA dehydrogenase (124122005)
 
Gene (location): HADH (4q25)
 
Monarch Initiative: MONDO:0017715
OMIM®: 231530
Orphanet: ORPHA309127

Definition

3-hydroxyacyl-CoA dehydrogenase deficiency is an inherited condition that prevents the body from converting certain fats to energy, particularly during prolonged periods without food (fasting).

Initial signs and symptoms of this disorder typically occur during infancy or early childhood and can include poor appetite, vomiting, diarrhea, and lack of energy (lethargy). Affected individuals can also have muscle weakness (hypotonia), liver problems, low blood glucose (hypoglycemia), and abnormally high levels of insulin (hyperinsulinism). Insulin controls the amount of glucose that moves from the blood into cells for conversion to energy. Individuals with 3-hydroxyacyl-CoA dehydrogenase deficiency are also at risk for complications such as seizures, life-threatening heart and breathing problems, coma, and sudden death. This condition may explain some cases of sudden infant death syndrome (SIDS), which is defined as unexplained death in babies younger than 1 year.

Problems related to 3-hydroxyacyl-CoA dehydrogenase deficiency can be triggered by periods of fasting or by illnesses such as viral infections. 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. [from MedlinePlus Genetics]

Clinical features

From HPO
Hereditary myoglobinuria
MedGen UID:
44557
Concept ID:
C0027080
Finding
Presence of myoglobin in the urine.
Dicarboxylic aciduria
MedGen UID:
343550
Concept ID:
C1856432
Finding
An increased concentration of dicarboxylic acid in the urine.
Primary dilated cardiomyopathy
MedGen UID:
2880
Concept ID:
C0007193
Disease or Syndrome
Familial dilated cardiomyopathy is a genetic form of heart disease. It occurs when heart (cardiac) muscle becomes thin and weakened in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated). As a result, the heart is unable to pump blood as efficiently as usual. To compensate, the heart attempts to increase the amount of blood being pumped through the heart, leading to further thinning and weakening of the cardiac muscle. Over time, this condition results in heart failure.\n\nIt usually takes many years for symptoms of familial dilated cardiomyopathy to cause health problems. They typically begin in mid-adulthood, but can occur at any time from infancy to late adulthood. Signs and symptoms of familial dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath (dyspnea), extreme tiredness (fatigue), fainting episodes (syncope), and swelling of the legs and feet. In some cases, the first sign of the disorder is sudden cardiac death. The severity of the condition varies among affected individuals, even in members of the same family.
Hypertrophic cardiomyopathy
MedGen UID:
2881
Concept ID:
C0007194
Disease or Syndrome
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.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Hepatic necrosis
MedGen UID:
57487
Concept ID:
C0151798
Disease or Syndrome
The presence of cell death (necrosis) affecting the liver.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Hepatic steatosis
MedGen UID:
398225
Concept ID:
C2711227
Disease or Syndrome
Steatosis is a term used to denote lipid accumulation within hepatocytes.
Fulminant hepatic failure
MedGen UID:
1830332
Concept ID:
C5779644
Disease or Syndrome
Hepatic failure refers to the inability of the liver to perform its normal synthetic and metabolic functions, which can result in coagulopathy and alteration in the mental status of a previously healthy individual. Hepatic failure is defined as fulminant if there is onset of encephalopathy within 4 weeks of the onset of symptoms in a patient with a previously healthy liver.
Hypoglycemic encephalopathy
MedGen UID:
101772
Concept ID:
C0149877
Disease or Syndrome
Brain damage related to a lowering of blood glucose below a critical level (around 30 mg/dl), which may lead to confusion, lethargy and delirium followed by seizures and coma. Prolonged hypoglycemia may lead to irreversible brain damage.
Hypoglycemic seizures
MedGen UID:
164079
Concept ID:
C0877056
Disease or Syndrome
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.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Hypoketotic hypoglycemia
MedGen UID:
344733
Concept ID:
C1856438
Finding
A decreased concentration of glucose in the blood associated with a reduced concentration of ketone bodies.
Decreased 3-hydroxyacyl-CoA dehydrogenase level
MedGen UID:
1381484
Concept ID:
C4477062
Finding

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDeficiency of 3-hydroxyacyl-CoA dehydrogenase
Follow this link to review classifications for Deficiency of 3-hydroxyacyl-CoA dehydrogenase in Orphanet.

Professional guidelines

PubMed

David J, Chrastina P, Pešková K, Kožich V, Friedecký D, Adam T, Hlídková E, Vinohradská H, Novotná D, Hedelová M, Al Taji E, Holubová A, Skalická V, Macek M, Gaillyová R, Votava F
Cent Eur J Public Health 2019 Jun;27(2):153-159. doi: 10.21101/cejph.a5441. PMID: 31241292
Kang E, Kim YM, Kang M, Heo SH, Kim GH, Choi IH, Choi JH, Yoo HW, Lee BH
BMC Pediatr 2018 Mar 8;18(1):103. doi: 10.1186/s12887-018-1069-z. PMID: 29519241Free PMC Article
Liu J, Ghaziani TT, Wolf JL
Am J Gastroenterol 2017 Jun;112(6):838-846. Epub 2017 Mar 14 doi: 10.1038/ajg.2017.54. PMID: 28291236

Curated

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

American College of Medical Genetics and Genomics, Algorithm, C4-OH Elevated: SCHAD Deficiency, 2022

Recent clinical studies

Etiology

Mütze U, Ottenberger A, Gleich F, Maier EM, Lindner M, Husain RA, Palm K, Beblo S, Freisinger P, Santer R, Thimm E, Vom Dahl S, Weinhold N, Grohmann-Held K, Haase C, Hennermann JB, Hörbe-Blindt A, Kamrath C, Marquardt I, Marquardt T, Behne R, Haas D, Spiekerkoetter U, Hoffmann GF, Garbade SF, Grünert SC, Kölker S
Ann Clin Transl Neurol 2024 Apr;11(4):883-898. Epub 2024 Jan 23 doi: 10.1002/acn3.52002. PMID: 38263760Free PMC Article
Liu J, Ghaziani TT, Wolf JL
Am J Gastroenterol 2017 Jun;112(6):838-846. Epub 2017 Mar 14 doi: 10.1038/ajg.2017.54. PMID: 28291236
Winter S, Buist NR, Longo N, Armenian SH, Lopaschuk G, Wasilewska A
Ann Nutr Metab 2016;68 Suppl 3:21-23. Epub 2016 Dec 9 doi: 10.1159/000448323. PMID: 27931031
den Boer ME, Wanders RJ, Morris AA, IJlst L, Heymans HS, Wijburg FA
Pediatrics 2002 Jan;109(1):99-104. doi: 10.1542/peds.109.1.99. PMID: 11773547
Tyni T, Pihko H
Acta Paediatr 1999 Mar;88(3):237-45. doi: 10.1080/08035259950169954. PMID: 10229030

Diagnosis

Liu J, Ghaziani TT, Wolf JL
Am J Gastroenterol 2017 Jun;112(6):838-846. Epub 2017 Mar 14 doi: 10.1038/ajg.2017.54. PMID: 28291236
Winter S, Buist NR, Longo N, Armenian SH, Lopaschuk G, Wasilewska A
Ann Nutr Metab 2016;68 Suppl 3:21-23. Epub 2016 Dec 9 doi: 10.1159/000448323. PMID: 27931031
Palladino AA, Stanley CA
Rev Endocr Metab Disord 2010 Sep;11(3):171-8. doi: 10.1007/s11154-010-9146-0. PMID: 20936362
Tyni T, Pihko H
Acta Paediatr 1999 Mar;88(3):237-45. doi: 10.1080/08035259950169954. PMID: 10229030
Tein I
Semin Pediatr Neurol 1996 Jun;3(2):59-98. doi: 10.1016/s1071-9091(96)80038-6. PMID: 8795843

Therapy

Wang H, Lu J, Chen X, Schwalbe M, Gorka JE, Mandel JA, Wang J, Goetzman ES, Ranganathan S, Dobrowolski SF, Prochownik EV
J Biol Chem 2021 Jan-Jun;296:100283. Epub 2021 Jan 13 doi: 10.1016/j.jbc.2021.100283. PMID: 33450224Free PMC Article
Winter S, Buist NR, Longo N, Armenian SH, Lopaschuk G, Wasilewska A
Ann Nutr Metab 2016;68 Suppl 3:21-23. Epub 2016 Dec 9 doi: 10.1159/000448323. PMID: 27931031
Immonen T, Turanlahti M, Paganus A, Keskinen P, Tyni T, Lapatto R
Acta Paediatr 2016 May;105(5):549-54. Epub 2016 Feb 5 doi: 10.1111/apa.13313. PMID: 26676313
Ribas GS, Vargas CR, Wajner M
Gene 2014 Jan 10;533(2):469-76. Epub 2013 Oct 19 doi: 10.1016/j.gene.2013.10.017. PMID: 24148561
Gillingham MB, Connor WE, Matern D, Rinaldo P, Burlingame T, Meeuws K, Harding CO
Mol Genet Metab 2003 Jun;79(2):114-23. doi: 10.1016/s1096-7192(03)00073-8. PMID: 12809642Free PMC Article

Prognosis

Mütze U, Ottenberger A, Gleich F, Maier EM, Lindner M, Husain RA, Palm K, Beblo S, Freisinger P, Santer R, Thimm E, Vom Dahl S, Weinhold N, Grohmann-Held K, Haase C, Hennermann JB, Hörbe-Blindt A, Kamrath C, Marquardt I, Marquardt T, Behne R, Haas D, Spiekerkoetter U, Hoffmann GF, Garbade SF, Grünert SC, Kölker S
Ann Clin Transl Neurol 2024 Apr;11(4):883-898. Epub 2024 Jan 23 doi: 10.1002/acn3.52002. PMID: 38263760Free PMC Article
Rücklová K, Hrubá E, Pavlíková M, Hanák P, Farolfi M, Chrastina P, Vlášková H, Kousal B, Smolka V, Foltenová H, Adam T, Friedecký D, Ješina P, Zeman J, Kožich V, Honzík T
Nutrients 2021 Aug 24;13(9) doi: 10.3390/nu13092925. PMID: 34578803Free PMC Article
Liu J, Ghaziani TT, Wolf JL
Am J Gastroenterol 2017 Jun;112(6):838-846. Epub 2017 Mar 14 doi: 10.1038/ajg.2017.54. PMID: 28291236
den Boer ME, Wanders RJ, Morris AA, IJlst L, Heymans HS, Wijburg FA
Pediatrics 2002 Jan;109(1):99-104. doi: 10.1542/peds.109.1.99. PMID: 11773547
Tyni T, Pihko H
Acta Paediatr 1999 Mar;88(3):237-45. doi: 10.1080/08035259950169954. PMID: 10229030

Clinical prediction guides

Rücklová K, Hrubá E, Pavlíková M, Hanák P, Farolfi M, Chrastina P, Vlášková H, Kousal B, Smolka V, Foltenová H, Adam T, Friedecký D, Ješina P, Zeman J, Kožich V, Honzík T
Nutrients 2021 Aug 24;13(9) doi: 10.3390/nu13092925. PMID: 34578803Free PMC Article
Liu J, Ghaziani TT, Wolf JL
Am J Gastroenterol 2017 Jun;112(6):838-846. Epub 2017 Mar 14 doi: 10.1038/ajg.2017.54. PMID: 28291236
Ribas GS, Vargas CR, Wajner M
Gene 2014 Jan 10;533(2):469-76. Epub 2013 Oct 19 doi: 10.1016/j.gene.2013.10.017. PMID: 24148561
Fletcher AL, Pennesi ME, Harding CO, Weleber RG, Gillingham MB
Mol Genet Metab 2012 May;106(1):18-24. Epub 2012 Mar 8 doi: 10.1016/j.ymgme.2012.02.015. PMID: 22459206Free PMC Article
Giurgea I, Bellanné-Chantelot C, Ribeiro M, Hubert L, Sempoux C, Robert JJ, Blankenstein O, Hussain K, Brunelle F, Nihoul-Fékété C, Rahier J, Jaubert F, de Lonlay P
Horm Res 2006;66(6):289-96. Epub 2006 Sep 26 doi: 10.1159/000095938. PMID: 17003566

Recent systematic reviews

Fraser H, Geppert J, Johnson R, Johnson S, Connock M, Clarke A, Taylor-Phillips S, Stinton C
Orphanet J Rare Dis 2019 Nov 15;14(1):258. doi: 10.1186/s13023-019-1226-y. PMID: 31730477Free PMC Article
Moorthie S, Cameron L, Sagoo GS, Bonham JR, Burton H
J Inherit Metab Dis 2014 Nov;37(6):889-98. Epub 2014 Jul 15 doi: 10.1007/s10545-014-9729-0. PMID: 25022222

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-OH Acylcarnitine, Short Chain Hydroxyacyl-CoA Dehydrogenase (SCHAD) Deficiency, 2022
    • ACMG Algorithm, 2022
      American College of Medical Genetics and Genomics, Algorithm, C4-OH Elevated: SCHAD Deficiency, 2022

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