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Oxoglutaricaciduria(OGDHD)

MedGen UID:
414553
Concept ID:
C2752074
Disease or Syndrome
Synonyms: 2 alpha ketoglutarate dehydrogenase deficiency; Alpha KGD deficiency; Alpha-ketoglutarate dehydrogenase deficiency
SNOMED CT: Deficiency of alpha-ketoglutarate dehydrogenase (733630004); Oxoglutaricaciduria (733630004)
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): OGDH (7p13)
 
Monarch Initiative: MONDO:0008759
OMIM®: 203740
Orphanet: ORPHA31

Definition

Oxoglutarate dehydrogenase deficiency (OGDHD) is an autosomal recessive disorder associated with features of infantile- and pediatric-onset basal ganglia-associated movement disorders, hypotonia, developmental delays, ataxia, and seizures (summary by Yap et al., 2021). [from OMIM]

Clinical features

From HPO
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Falls
MedGen UID:
39084
Concept ID:
C0085639
Finding
A sudden movement downward, usually resulting in injury.
Unsteady gait
MedGen UID:
68544
Concept ID:
C0231686
Finding
A shaky or wobbly manner of walking.
Dysmetria
MedGen UID:
68583
Concept ID:
C0234162
Finding
A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.
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.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
Gait ataxia
MedGen UID:
155642
Concept ID:
C0751837
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
Delayed gross motor development
MedGen UID:
332508
Concept ID:
C1837658
Finding
A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
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.
Rigidity
MedGen UID:
7752
Concept ID:
C0026837
Sign or Symptom
Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.
Generalized amyotrophy
MedGen UID:
234650
Concept ID:
C1389113
Disease or Syndrome
Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles.
Metabolic acidosis
MedGen UID:
65117
Concept ID:
C0220981
Pathologic Function
Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause.
Increased circulating lactate concentration
MedGen UID:
332209
Concept ID:
C1836440
Finding
Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35).
Congenital lactic acidosis
MedGen UID:
870818
Concept ID:
C4025276
Disease or Syndrome
A form of lactic acidemia with congenital onset.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVOxoglutaricaciduria
Follow this link to review classifications for Oxoglutaricaciduria in Orphanet.

Recent clinical studies

Etiology

Tort F, Ferrer-Cortès X, Thió M, Navarro-Sastre A, Matalonga L, Quintana E, Bujan N, Arias A, García-Villoria J, Acquaviva C, Vianey-Saban C, Artuch R, García-Cazorla À, Briones P, Ribes A
Hum Mol Genet 2014 Apr 1;23(7):1907-15. Epub 2013 Nov 20 doi: 10.1093/hmg/ddt585. PMID: 24256811
De Vivo DC
Brain Dev 1993 Jan-Feb;15(1):1-22. doi: 10.1016/0387-7604(93)90002-p. PMID: 8338207

Diagnosis

López GP, Quispe BV, Cabrejas Núñez MJ, Castaño L, Barrio R
J Clin Res Pediatr Endocrinol 2017 Dec 15;9(4):355-359. Epub 2017 Apr 7 doi: 10.4274/jcrpe.4324. PMID: 28387648Free PMC Article

Prognosis

Whittle EF, Chilian M, Karimiani EG, Progri H, Buhas D, Kose M, Ganetzky RD, Toosi MB, Torbati PN, Badv RS, Shelihan I, Yang H, Elloumi HZ, Lee S, Jamshidi Y, Pittman AM, Houlden H, Ignatius E, Rahman S, Maroofian R, Yoon WH, Carroll CJ
Genet Med 2023 Feb;25(2):100332. Epub 2022 Dec 15 doi: 10.1016/j.gim.2022.11.001. PMID: 36520152Free PMC Article
Smith AC, Robinson AJ
BMC Syst Biol 2011 Jun 29;5:102. doi: 10.1186/1752-0509-5-102. PMID: 21714867Free PMC Article
Odièvre MH, Chretien D, Munnich A, Robinson BH, Dumoulin R, Masmoudi S, Kadhom N, Rötig A, Rustin P, Bonnefont JP
Hum Mutat 2005 Mar;25(3):323-4. doi: 10.1002/humu.9319. PMID: 15712224

Clinical prediction guides

Whittle EF, Chilian M, Karimiani EG, Progri H, Buhas D, Kose M, Ganetzky RD, Toosi MB, Torbati PN, Badv RS, Shelihan I, Yang H, Elloumi HZ, Lee S, Jamshidi Y, Pittman AM, Houlden H, Ignatius E, Rahman S, Maroofian R, Yoon WH, Carroll CJ
Genet Med 2023 Feb;25(2):100332. Epub 2022 Dec 15 doi: 10.1016/j.gim.2022.11.001. PMID: 36520152Free PMC Article
Smith AC, Robinson AJ
BMC Syst Biol 2011 Jun 29;5:102. doi: 10.1186/1752-0509-5-102. PMID: 21714867Free PMC Article
Odièvre MH, Chretien D, Munnich A, Robinson BH, Dumoulin R, Masmoudi S, Kadhom N, Rötig A, Rustin P, Bonnefont JP
Hum Mutat 2005 Mar;25(3):323-4. doi: 10.1002/humu.9319. PMID: 15712224

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