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Glutaric aciduria

MedGen UID:
75695
Concept ID:
C0268594
Disease or Syndrome
Synonym: Glutaricaciduria
SNOMED CT: Glutaric aciduria (28987007)
 
HPO: HP:0003150
Monarch Initiative: MONDO:0000129

Definition

The concentration of glutaric acid in the urine, normalized for urine concentration, is above the upper limit of normal. [from HPO]

Conditions with this feature

Glutaric aciduria, type 1
MedGen UID:
124337
Concept ID:
C0268595
Disease or Syndrome
The phenotypic spectrum of untreated glutaric acidemia type 1 (GA-1) ranges from the more common form (infantile-onset disease) to the less common form (later-onset disease – i.e., after age 6 years). Of note, the GA-1 phenotype can vary widely between untreated family members with the same genotype, primarily as a function of the age at which the first acute encephalopathic crisis occurred: three months to six years in infantile-onset GA-1 and after age six years in later-onset GA-1. Characteristically these crises result in acute bilateral striatal injury and subsequent complex movement disorders. In the era of newborn screening (NBS), the prompt initiation of treatment of asymptomatic infants detected by NBS means that most individuals who would have developed manifestations of either infantile-onset or later-onset GA-1 remain asymptomatic; however, they may be at increased risk for other manifestations (e.g., renal disease) that are becoming apparent as the understanding of the natural history of treated GA-1 continues to evolve.
Multiple acyl-CoA dehydrogenase deficiency
MedGen UID:
75696
Concept ID:
C0268596
Disease or Syndrome
Multiple acyl-CoA dehydrogenase deficiency (MADD) represents a clinical spectrum in which presentations can be divided into type I (neonatal onset with congenital anomalies), type II (neonatal onset without congenital anomalies), and type III (late onset). Individuals with type I or II MADD typically become symptomatic in the neonatal period with severe metabolic acidosis, which may be accompanied by profound hypoglycemia and hyperammonemia. Many affected individuals die in the newborn period despite metabolic treatment. In those who survive the neonatal period, recurrent metabolic decompensation resembling Reye syndrome and the development of hypertrophic cardiomyopathy can occur. Congenital anomalies may include dysmorphic facial features, large cystic kidneys, hypospadias and chordee in males, and neuronal migration defects (heterotopias) on brain MRI. Individuals with type III MADD, the most common presentation, can present from infancy to adulthood. The most common symptoms are muscle weakness, exercise intolerance, and/or muscle pain, although metabolic decompensation with episodes of rhabdomyolysis can also be seen. Rarely, individuals with late-onset MADD (type III) may develop severe sensory neuropathy in addition to proximal myopathy.
Deficiency of hydroxymethylglutaryl-CoA lyase
MedGen UID:
78692
Concept ID:
C0268601
Disease or Syndrome
3-Hydroxy-3-methylglutaryl-CoA lyase deficiency (HMGCLD) is a rare autosomal recessive disorder with the cardinal manifestations of metabolic acidosis without ketonuria, hypoglycemia, and a characteristic pattern of elevated urinary organic acid metabolites, including 3-hydroxy-3-methylglutaric, 3-methylglutaric, and 3-hydroxyisovaleric acids. Urinary levels of 3-methylcrotonylglycine may be increased. Dicarboxylic aciduria, hepatomegaly, and hyperammonemia may also be observed. Presenting clinical signs include irritability, lethargy, coma, and vomiting (summary by Gibson et al., 1988).
Glutaryl-CoA oxidase deficiency
MedGen UID:
87464
Concept ID:
C0342873
Disease or Syndrome
Glutaric aciduria III is characterized by an isolated accumulation of glutaric acid. It appears to be a 'non-disease' as it is found in healthy individuals and is associated with inconsistent symptoms in others (summary by Marlaire et al., 2014).
D-2-hydroxyglutaric aciduria 1
MedGen UID:
463405
Concept ID:
C3152055
Disease or Syndrome
D-2-hydroxyglutaric aciduria is a neurometabolic disorder first described by Chalmers et al. (1980). Clinical symptoms include developmental delay, epilepsy, hypotonia, and dysmorphic features. Mild and severe phenotypes were characterized (van der Knaap et al., 1999). The severe phenotype is homogeneous and is characterized by early infantile-onset epileptic encephalopathy and, often, cardiomyopathy. The mild phenotype has a more variable clinical presentation. Genetic Heterogeneity of D-2-Hydroxyglutaric Aciduria D-2-hydroxyglutaric aciduria-2 (D2HGA2; 613657) is caused by heterozygous mutation in the mitochondrial isocitrate dehydrogenase-2 gene (IDH2; 147650) on chromosome 15q26.

Professional guidelines

PubMed

Schuurmans IME, Dimitrov B, Schröter J, Ribes A, de la Fuente RP, Zamora B, van Karnebeek CDM, Kölker S, Garanto A
J Inherit Metab Dis 2023 May;46(3):371-390. Epub 2023 Apr 16 doi: 10.1002/jimd.12608. PMID: 37020324
Tuncel AT, Boy N, Morath MA, Hörster F, Mütze U, Kölker S
J Inherit Metab Dis 2018 Sep;41(5):765-776. Epub 2018 Jan 15 doi: 10.1007/s10545-017-0135-2. PMID: 29335813
Kölker S, Christensen E, Leonard JV, Greenberg CR, Boneh A, Burlina AB, Burlina AP, Dixon M, Duran M, García Cazorla A, Goodman SI, Koeller DM, Kyllerman M, Mühlhausen C, Müller E, Okun JG, Wilcken B, Hoffmann GF, Burgard P
J Inherit Metab Dis 2011 Jun;34(3):677-94. Epub 2011 Mar 23 doi: 10.1007/s10545-011-9289-5. PMID: 21431622Free PMC Article

Recent clinical studies

Etiology

Bian B, Liu Z, Feng D, Li W, Wang L, Li Y, Li D
AJNR Am J Neuroradiol 2023 Aug;44(8):967-973. Epub 2023 Jul 20 doi: 10.3174/ajnr.A7928. PMID: 37474264Free PMC Article
Boy N, Mühlhausen C, Maier EM, Ballhausen D, Baumgartner MR, Beblo S, Burgard P, Chapman KA, Dobbelaere D, Heringer-Seifert J, Fleissner S, Grohmann-Held K, Hahn G, Harting I, Hoffmann GF, Jochum F, Karall D, Konstantopoulous V, Krawinkel MB, Lindner M, Märtner EMC, Nuoffer JM, Okun JG, Plecko B, Posset R, Sahm K, Scholl-Bürgi S, Thimm E, Walter M, Williams M, Vom Dahl S, Ziagaki A, Zschocke J, Kölker S
J Inherit Metab Dis 2023 May;46(3):482-519. Epub 2022 Nov 17 doi: 10.1002/jimd.12566. PMID: 36221165
Chen YC, Huang CY, Lee YT, Wu CH, Chang SK, Cheng HL, Chang PH, Niu DM, Cheng YF
Orphanet J Rare Dis 2020 Dec 1;15(1):337. doi: 10.1186/s13023-020-01571-w. PMID: 33256818Free PMC Article
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Roujeau T, Mireau E, Bourgeois M
Handb Clin Neurol 2013;112:905-12. doi: 10.1016/B978-0-444-52910-7.00012-X. PMID: 23622300

Diagnosis

Boy N, Mühlhausen C, Maier EM, Ballhausen D, Baumgartner MR, Beblo S, Burgard P, Chapman KA, Dobbelaere D, Heringer-Seifert J, Fleissner S, Grohmann-Held K, Hahn G, Harting I, Hoffmann GF, Jochum F, Karall D, Konstantopoulous V, Krawinkel MB, Lindner M, Märtner EMC, Nuoffer JM, Okun JG, Plecko B, Posset R, Sahm K, Scholl-Bürgi S, Thimm E, Walter M, Williams M, Vom Dahl S, Ziagaki A, Zschocke J, Kölker S
J Inherit Metab Dis 2023 May;46(3):482-519. Epub 2022 Nov 17 doi: 10.1002/jimd.12566. PMID: 36221165
Bouchereau J, Schiff M
J Nutr 2020 Oct 1;150(Suppl 1):2556S-2560S. doi: 10.1093/jn/nxaa112. PMID: 33000154
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Renaud DL
Semin Neurol 2012 Feb;32(1):34-41. Epub 2012 Mar 15 doi: 10.1055/s-0032-1306384. PMID: 22422204
Kölker S, Christensen E, Leonard JV, Greenberg CR, Boneh A, Burlina AB, Burlina AP, Dixon M, Duran M, García Cazorla A, Goodman SI, Koeller DM, Kyllerman M, Mühlhausen C, Müller E, Okun JG, Wilcken B, Hoffmann GF, Burgard P
J Inherit Metab Dis 2011 Jun;34(3):677-94. Epub 2011 Mar 23 doi: 10.1007/s10545-011-9289-5. PMID: 21431622Free PMC Article

Therapy

Bisschoff M, Smuts I, Dercksen M, Schoonen M, Vorster BC, van der Watt G, Spencer C, Naidu K, Henning F, Meldau S, McFarland R, Taylor RW, Patel K, Fassad MR, Vandrovcova J; ICGNMD Consortium, Wanders RJA, van der Westhuizen FH
Orphanet J Rare Dis 2024 Jan 14;19(1):15. doi: 10.1186/s13023-023-03014-8. PMID: 38221620Free PMC Article
Bouchereau J, Schiff M
J Nutr 2020 Oct 1;150(Suppl 1):2556S-2560S. doi: 10.1093/jn/nxaa112. PMID: 33000154
Nasser M, Javaheri H, Fedorowicz Z, Noorani Z
Cochrane Database Syst Rev 2012 Feb 15;2012(2):CD006659. doi: 10.1002/14651858.CD006659.pub3. PMID: 22336821Free PMC Article
Nasser M, Javaheri H, Fedorowicz Z, Noorani Z
Cochrane Database Syst Rev 2009 Apr 15;(2):CD006659. doi: 10.1002/14651858.CD006659.pub2. PMID: 19370646
Greene P
Clin Neuropharmacol 1992 Aug;15(4):276-88. doi: 10.1097/00002826-199208000-00002. PMID: 1516073

Prognosis

Schuurmans IME, Dimitrov B, Schröter J, Ribes A, de la Fuente RP, Zamora B, van Karnebeek CDM, Kölker S, Garanto A
J Inherit Metab Dis 2023 May;46(3):371-390. Epub 2023 Apr 16 doi: 10.1002/jimd.12608. PMID: 37020324
Gürbüz BB, Yılmaz DY, Coşkun T, Tokatlı A, Dursun A, Sivri HS
Eur J Med Genet 2020 Nov;63(11):104032. Epub 2020 Aug 7 doi: 10.1016/j.ejmg.2020.104032. PMID: 32777384
Tuncel AT, Boy N, Morath MA, Hörster F, Mütze U, Kölker S
J Inherit Metab Dis 2018 Sep;41(5):765-776. Epub 2018 Jan 15 doi: 10.1007/s10545-017-0135-2. PMID: 29335813
Roujeau T, Mireau E, Bourgeois M
Handb Clin Neurol 2013;112:905-12. doi: 10.1016/B978-0-444-52910-7.00012-X. PMID: 23622300
Kölker S, Christensen E, Leonard JV, Greenberg CR, Boneh A, Burlina AB, Burlina AP, Dixon M, Duran M, García Cazorla A, Goodman SI, Koeller DM, Kyllerman M, Mühlhausen C, Müller E, Okun JG, Wilcken B, Hoffmann GF, Burgard P
J Inherit Metab Dis 2011 Jun;34(3):677-94. Epub 2011 Mar 23 doi: 10.1007/s10545-011-9289-5. PMID: 21431622Free PMC Article

Clinical prediction guides

Barroso M, Gertzen M, Puchwein-Schwepcke AF, Preisler H, Sturm A, Reiss DD, Danecka MK, Muntau AC, Gersting SW
Int J Mol Sci 2023 Aug 24;24(17) doi: 10.3390/ijms241713158. PMID: 37685964Free PMC Article
Bian B, Liu Z, Feng D, Li W, Wang L, Li Y, Li D
AJNR Am J Neuroradiol 2023 Aug;44(8):967-973. Epub 2023 Jul 20 doi: 10.3174/ajnr.A7928. PMID: 37474264Free PMC Article
Schuurmans IME, Dimitrov B, Schröter J, Ribes A, de la Fuente RP, Zamora B, van Karnebeek CDM, Kölker S, Garanto A
J Inherit Metab Dis 2023 May;46(3):371-390. Epub 2023 Apr 16 doi: 10.1002/jimd.12608. PMID: 37020324
Ali A, Almesmari FSA, Dhahouri NA, Saleh Ali AM, Aldhanhani MAAMA, Vijayan R, Al Tenaiji A, Al Shamsi A, Hertecant J, Al Jasmi F
Genes (Basel) 2021 Aug 27;12(9) doi: 10.3390/genes12091334. PMID: 34573316Free PMC Article
Kölker S, Christensen E, Leonard JV, Greenberg CR, Boneh A, Burlina AB, Burlina AP, Dixon M, Duran M, García Cazorla A, Goodman SI, Koeller DM, Kyllerman M, Mühlhausen C, Müller E, Okun JG, Wilcken B, Hoffmann GF, Burgard P
J Inherit Metab Dis 2011 Jun;34(3):677-94. Epub 2011 Mar 23 doi: 10.1007/s10545-011-9289-5. PMID: 21431622Free PMC Article

Recent systematic reviews

Boy N, Mengler K, Heringer-Seifert J, Hoffmann GF, Garbade SF, Kölker S
Genet Med 2021 Jan;23(1):13-21. Epub 2020 Sep 28 doi: 10.1038/s41436-020-00971-4. PMID: 32981931Free PMC Article
Vester ME, Bilo RA, Karst WA, Daams JG, Duijst WL, van Rijn RR
Forensic Sci Med Pathol 2015 Sep;11(3):405-15. Epub 2015 Jul 29 doi: 10.1007/s12024-015-9698-0. PMID: 26219480Free 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
Nasser M, Javaheri H, Fedorowicz Z, Noorani Z
Cochrane Database Syst Rev 2012 Feb 15;2012(2):CD006659. doi: 10.1002/14651858.CD006659.pub3. PMID: 22336821Free PMC Article
Nasser M, Javaheri H, Fedorowicz Z, Noorani Z
Cochrane Database Syst Rev 2009 Apr 15;(2):CD006659. doi: 10.1002/14651858.CD006659.pub2. PMID: 19370646

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