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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-Coenzyme A Dehydrogenase Deficiency; 3-hydroxylacyl-CoA dehydrogenase deficiency; M/SCHAD; Medium and short chain 3-hydroxyacyl-CoA dehydrogenase 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). [HPO:curators]
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
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)
OMIM®: 231530

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 sugar (hypoglycemia), and abnormally high levels of insulin (hyperinsulinism). Insulin controls the amount of sugar 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 GHR]

Clinical features

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.It 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
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.
Myoglobinuria
MedGen UID:
44557
Concept ID:
C0027080
Finding
Presence of myoglobin in the urine.
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.
Hepatic necrosis
MedGen UID:
57487
Concept ID:
C0151798
Disease or Syndrome
A necrotic process affecting the hepatic parenchyma.
Acute hepatic failure
MedGen UID:
58125
Concept ID:
C0162557
Disease or Syndrome
A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C.
Hypoglycemic seizures
MedGen UID:
164079
Concept ID:
C0877056
Disease or Syndrome
Dicarboxylic aciduria
MedGen UID:
343550
Concept ID:
C1856432
Finding
An increased concentration of dicarboxylic acid in the urine.
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.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
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
Inflammation of the liver related to lipid accumulation in fatty liver.
Growth delay
MedGen UID:
765377
Concept ID:
C3552463
Sign or Symptom
A deficiency or slowing down of growth pre- and postnatally.

Recent clinical studies

Etiology

Yonekawa Y, Thomas BJ, Capone A Jr
JAMA Ophthalmol 2016 Apr;134(4):e155033. Epub 2016 Apr 14 doi: 10.1001/jamaophthalmol.2015.5033. PMID: 27078015
Haglind CB, Nordenström A, Ask S, von Döbeln U, Gustafsson J, Stenlid MH
J Inherit Metab Dis 2015 Mar;38(2):315-22. Epub 2014 Aug 21 doi: 10.1007/s10545-014-9750-3. PMID: 25141826
Sykut-Cegielska J, Gradowska W, Piekutowska-Abramczuk D, Andresen BS, Olsen RK, Ołtarzewski M, Pronicki M, Pajdowska M, Bogdańska A, Jabłońska E, Radomyska B, Kuśmierska K, Krajewska-Walasek M, Gregersen N, Pronicka E
J Inherit Metab Dis 2011 Feb;34(1):185-95. Epub 2010 Nov 20 doi: 10.1007/s10545-010-9244-x. PMID: 21103935
Piekutowska-Abramczuk D, Olsen RK, Wierzba J, Popowska E, Jurkiewicz D, Ciara E, Ołtarzewski M, Gradowska W, Sykut-Cegielska J, Krajewska-Walasek M, Andresen BS, Gregersen N, Pronicka E
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S373-7. Epub 2010 Sep 3 doi: 10.1007/s10545-010-9190-7. PMID: 20814823
Sturm V
Eur J Ophthalmol 2008 May-Jun;18(3):476-8. PMID: 18465739

Diagnosis

Yonekawa Y, Thomas BJ, Capone A Jr
JAMA Ophthalmol 2016 Apr;134(4):e155033. Epub 2016 Apr 14 doi: 10.1001/jamaophthalmol.2015.5033. PMID: 27078015
Haglind CB, Nordenström A, Ask S, von Döbeln U, Gustafsson J, Stenlid MH
J Inherit Metab Dis 2015 Mar;38(2):315-22. Epub 2014 Aug 21 doi: 10.1007/s10545-014-9750-3. PMID: 25141826
Heslegrave AJ, Hussain K
J Clin Endocrinol Metab 2013 Feb;98(2):496-501. Epub 2012 Dec 18 doi: 10.1210/jc.2012-3134. PMID: 23253615
Vilarinho L, Marques JS, Rocha H, Ramos A, Lopes L, Narayan SB, Bennett MJ
Mol Genet Metab 2012 Jul;106(3):277-80. Epub 2012 Apr 13 doi: 10.1016/j.ymgme.2012.04.005. PMID: 22579592
Sykut-Cegielska J, Gradowska W, Piekutowska-Abramczuk D, Andresen BS, Olsen RK, Ołtarzewski M, Pronicki M, Pajdowska M, Bogdańska A, Jabłońska E, Radomyska B, Kuśmierska K, Krajewska-Walasek M, Gregersen N, Pronicka E
J Inherit Metab Dis 2011 Feb;34(1):185-95. Epub 2010 Nov 20 doi: 10.1007/s10545-010-9244-x. PMID: 21103935

Therapy

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
Martin JM, Gillingham MB, Harding CO
Mol Genet Metab 2014 Jun;112(2):139-42. Epub 2014 Apr 6 doi: 10.1016/j.ymgme.2014.03.012. PMID: 24780638Free PMC Article
Blake F, Blessmann M, Werle H, Li L, Gbara A
Int J Paediatr Dent 2007 Jan;17(1):72-4. doi: 10.1111/j.1365-263X.2006.00763.x. PMID: 17181583
Lundy CT, Shield JP, Kvittingen EA, Vinorum OJ, Trimble ER, Morris AA
J Inherit Metab Dis 2003;26(6):537-41. PMID: 14605499
Gillingham MB, Connor WE, Matern D, Rinaldo P, Burlingame T, Meeuws K, Harding CO
Mol Genet Metab 2003 Jun;79(2):114-23. PMID: 12809642Free PMC Article

Prognosis

Yonekawa Y, Thomas BJ, Capone A Jr
JAMA Ophthalmol 2016 Apr;134(4):e155033. Epub 2016 Apr 14 doi: 10.1001/jamaophthalmol.2015.5033. PMID: 27078015
Martins E, Cardoso ML, Rodrigues E, Barbot C, Ramos A, Bennett MJ, Teles EL, Vilarinho L
J Inherit Metab Dis 2011 Jun;34(3):835-42. Epub 2011 Feb 24 doi: 10.1007/s10545-011-9287-7. PMID: 21347589
Sykut-Cegielska J, Gradowska W, Piekutowska-Abramczuk D, Andresen BS, Olsen RK, Ołtarzewski M, Pronicki M, Pajdowska M, Bogdańska A, Jabłońska E, Radomyska B, Kuśmierska K, Krajewska-Walasek M, Gregersen N, Pronicka E
J Inherit Metab Dis 2011 Feb;34(1):185-95. Epub 2010 Nov 20 doi: 10.1007/s10545-010-9244-x. PMID: 21103935
Piekutowska-Abramczuk D, Olsen RK, Wierzba J, Popowska E, Jurkiewicz D, Ciara E, Ołtarzewski M, Gradowska W, Sykut-Cegielska J, Krajewska-Walasek M, Andresen BS, Gregersen N, Pronicka E
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S373-7. Epub 2010 Sep 3 doi: 10.1007/s10545-010-9190-7. PMID: 20814823
Sturm V
Eur J Ophthalmol 2008 May-Jun;18(3):476-8. PMID: 18465739

Clinical prediction guides

Heslegrave AJ, Hussain K
J Clin Endocrinol Metab 2013 Feb;98(2):496-501. Epub 2012 Dec 18 doi: 10.1210/jc.2012-3134. PMID: 23253615
Martins E, Cardoso ML, Rodrigues E, Barbot C, Ramos A, Bennett MJ, Teles EL, Vilarinho L
J Inherit Metab Dis 2011 Jun;34(3):835-42. Epub 2011 Feb 24 doi: 10.1007/s10545-011-9287-7. PMID: 21347589
Pepin E, Guay C, Delghingaro-Augusto V, Joly E, Madiraju SR, Prentki M
J Diabetes 2010 Sep;2(3):157-67. doi: 10.1111/j.1753-0407.2010.00076.x. PMID: 20923481
Piekutowska-Abramczuk D, Olsen RK, Wierzba J, Popowska E, Jurkiewicz D, Ciara E, Ołtarzewski M, Gradowska W, Sykut-Cegielska J, Krajewska-Walasek M, Andresen BS, Gregersen N, Pronicka E
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S373-7. Epub 2010 Sep 3 doi: 10.1007/s10545-010-9190-7. PMID: 20814823
Tyni T, Paetau A, Strauss AW, Middleton B, Kivelä T
Pediatr Res 2004 Nov;56(5):744-50. Epub 2004 Sep 3 doi: 10.1203/01.PDR.0000141967.52759.83. PMID: 15347768

Recent systematic reviews

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

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