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Gamma-aminobutyric acid transaminase deficiency(GABATD)

MedGen UID:
137977
Concept ID:
C0342708
Disease or Syndrome
Synonyms: 4 alpha aminobutyrate transaminase deficiency; GABA aminotransaminase deficiency; GABA transaminase deficiency; GABATD; Gamma aminobutyrate transaminase deficiency
SNOMED CT: Gamma-aminobutyric acid transaminase deficiency (237941007)
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): ABAT (16p13.2)
 
Monarch Initiative: MONDO:0013166
OMIM®: 613163
Orphanet: ORPHA2066

Definition

GABA-transaminase deficiency (GABATD) is characterized by neonatal or early infantile-onset encephalopathy, hypotonia, hypersomnolence, epilepsy, choreoathetosis, and accelerated linear growth. Electroencephalograms show burst-suppression, modified hypsarrhythmia, multifocal spikes, and generalized spike-wave. Severity varies, but most patients have profound developmental impairment and some patients die in infancy (summary by Koenig et al., 2017). [from OMIM]

Additional description

From MedlinePlus Genetics
GABA-transaminase deficiency is a brain disease (encephalopathy) that begins in infancy. Babies with this disorder have recurrent seizures (epilepsy), uncontrolled limb movements (choreoathetosis), exaggerated reflexes (hyperreflexia), weak muscle tone (hypotonia), and excessive sleepiness (hypersomnolence). Affected babies may grow faster in length than usual (accelerated linear growth), even though they have feeding problems and may not gain weight as quickly as expected (failure to thrive).

Children with GABA-transaminase deficiency have profoundly impaired development. Most do not achieve normal developmental milestones of infancy such as following others' movement with their eyes or sitting unassisted. Individuals with this disorder usually do not survive past the first 2 years of life, but some live longer into childhood.  https://medlineplus.gov/genetics/condition/gaba-transaminase-deficiency

Clinical features

From HPO
Tall stature
MedGen UID:
69137
Concept ID:
C0241240
Finding
A height above that which is expected according to age and gender norms.
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.
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.
Leukodystrophy
MedGen UID:
6070
Concept ID:
C0023520
Disease or Syndrome
Leukodystrophy refers to deterioration of white matter of the brain resulting from degeneration of myelin sheaths in the CNS. Their basic defect is directly related to the synthesis and maintenance of myelin membranes. Symmetric white matter involvement at MRI is a typical finding in patients with leukodystrophies.
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.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
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.
Posterior fossa cyst
MedGen UID:
341753
Concept ID:
C1857353
Finding
A discrete posterior fossa cerebrospinal fluid (CSF) collection that does not communicate directly with the fourth ventricle.
EEG with burst suppression
MedGen UID:
369943
Concept ID:
C1969156
Finding
The burst suppression pattern in electroencephalography refers to a characteristic periodic pattern of low voltage (<10 microvolts) suppressed background and a relatively shorter pattern of higher amplitude slow, sharp, and spiking complexes.
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.
Retrognathia
MedGen UID:
19766
Concept ID:
C0035353
Congenital Abnormality
An abnormality in which the mandible is mislocalised posteriorly.
High-pitched cry
MedGen UID:
116082
Concept ID:
C0239154
Finding
A type of crying in an abnormally high-pitched voice.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVGamma-aminobutyric acid transaminase deficiency
Follow this link to review classifications for Gamma-aminobutyric acid transaminase deficiency in Orphanet.

Professional guidelines

PubMed

Mancuso M, Papadopoulou MT, Ng YS, Ardissone A, Bellusci M, Bertini E, Di Vito L, Evangelista T, Fons C, Hikmat O, Horvath R, Klopstock T, Kornblum C, Lamperti C, Licchetta L, Molnar MJ, Varhaug KN, O'Callaghan M, Pressler RM, Schiff M, Servidei S, Szabo N, Gorman GS, Cross JH, Rahman S
Eur J Neurol 2024 Jul;31(7):e16275. Epub 2024 Apr 4 doi: 10.1111/ene.16275. PMID: 38576261

Recent clinical studies

Etiology

Mancuso M, Papadopoulou MT, Ng YS, Ardissone A, Bellusci M, Bertini E, Di Vito L, Evangelista T, Fons C, Hikmat O, Horvath R, Klopstock T, Kornblum C, Lamperti C, Licchetta L, Molnar MJ, Varhaug KN, O'Callaghan M, Pressler RM, Schiff M, Servidei S, Szabo N, Gorman GS, Cross JH, Rahman S
Eur J Neurol 2024 Jul;31(7):e16275. Epub 2024 Apr 4 doi: 10.1111/ene.16275. PMID: 38576261
Koenig MK, Hodgeman R, Riviello JJ, Chung W, Bain J, Chiriboga CA, Ichikawa K, Osaka H, Tsuji M, Gibson KM, Bonnen PE, Pearl PL
Neurology 2017 May 16;88(20):1919-1924. Epub 2017 Apr 14 doi: 10.1212/WNL.0000000000003936. PMID: 28411234Free PMC Article

Diagnosis

Hegde AU, Karnavat PK, Vyas R, DiBacco ML, Grant PE, Pearl PL
J Child Neurol 2019 Mar;34(4):216-220. Epub 2019 Jan 15 doi: 10.1177/0883073818823359. PMID: 30644311Free PMC Article
Koenig MK, Hodgeman R, Riviello JJ, Chung W, Bain J, Chiriboga CA, Ichikawa K, Osaka H, Tsuji M, Gibson KM, Bonnen PE, Pearl PL
Neurology 2017 May 16;88(20):1919-1924. Epub 2017 Apr 14 doi: 10.1212/WNL.0000000000003936. PMID: 28411234Free PMC Article
Besse A, Petersen AK, Hunter JV, Appadurai V, Lalani SR, Bonnen PE
Mol Brain 2016 Dec 1;9(1):93. doi: 10.1186/s13041-016-0273-8. PMID: 27903293Free PMC Article
Louro P, Ramos L, Robalo C, Cancelinha C, Dinis A, Veiga R, Pina R, Rebelo O, Pop A, Diogo L, Salomons GS, Garcia P
J Inherit Metab Dis 2016 Sep;39(5):743-747. Epub 2016 Jul 4 doi: 10.1007/s10545-016-9951-z. PMID: 27376954

Therapy

Mancuso M, Papadopoulou MT, Ng YS, Ardissone A, Bellusci M, Bertini E, Di Vito L, Evangelista T, Fons C, Hikmat O, Horvath R, Klopstock T, Kornblum C, Lamperti C, Licchetta L, Molnar MJ, Varhaug KN, O'Callaghan M, Pressler RM, Schiff M, Servidei S, Szabo N, Gorman GS, Cross JH, Rahman S
Eur J Neurol 2024 Jul;31(7):e16275. Epub 2024 Apr 4 doi: 10.1111/ene.16275. PMID: 38576261
Kirby TO, Brown M, Ochoa-Repáraz J, Roullet JB, Gibson KM
Clin Pharmacol Ther 2019 Sep;106(3):505-507. Epub 2019 Jul 4 doi: 10.1002/cpt.1503. PMID: 31273774Free PMC Article
Koenig MK, Hodgeman R, Riviello JJ, Chung W, Bain J, Chiriboga CA, Ichikawa K, Osaka H, Tsuji M, Gibson KM, Bonnen PE, Pearl PL
Neurology 2017 May 16;88(20):1919-1924. Epub 2017 Apr 14 doi: 10.1212/WNL.0000000000003936. PMID: 28411234Free PMC Article

Prognosis

Mancuso M, Papadopoulou MT, Ng YS, Ardissone A, Bellusci M, Bertini E, Di Vito L, Evangelista T, Fons C, Hikmat O, Horvath R, Klopstock T, Kornblum C, Lamperti C, Licchetta L, Molnar MJ, Varhaug KN, O'Callaghan M, Pressler RM, Schiff M, Servidei S, Szabo N, Gorman GS, Cross JH, Rahman S
Eur J Neurol 2024 Jul;31(7):e16275. Epub 2024 Apr 4 doi: 10.1111/ene.16275. PMID: 38576261
Koenig MK, Hodgeman R, Riviello JJ, Chung W, Bain J, Chiriboga CA, Ichikawa K, Osaka H, Tsuji M, Gibson KM, Bonnen PE, Pearl PL
Neurology 2017 May 16;88(20):1919-1924. Epub 2017 Apr 14 doi: 10.1212/WNL.0000000000003936. PMID: 28411234Free PMC Article
Besse A, Petersen AK, Hunter JV, Appadurai V, Lalani SR, Bonnen PE
Mol Brain 2016 Dec 1;9(1):93. doi: 10.1186/s13041-016-0273-8. PMID: 27903293Free PMC Article

Clinical prediction guides

Besse A, Petersen AK, Hunter JV, Appadurai V, Lalani SR, Bonnen PE
Mol Brain 2016 Dec 1;9(1):93. doi: 10.1186/s13041-016-0273-8. PMID: 27903293Free PMC Article

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