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Glutamate pyruvate transaminase 2 deficiency(NEDSPM)

MedGen UID:
906606
Concept ID:
C4225388
Disease or Syndrome
Synonyms: NEDSPM; Neurodevelopmental disorder with microcephaly and spastic paraplegia
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): GPT2 (16q11.2)
 
Monarch Initiative: MONDO:0014567
OMIM®: 616281
Orphanet: ORPHA477673

Definition

Neurodevelopmental disorder with spastic paraplegia and microcephaly (NEDSPM) is an autosomal recessive neurologic syndrome characterized by delayed psychomotor development with delayed walking, moderately to severely impaired intellectual development, and poor or absent speech. More severely affected individuals show poor overall growth with progressive microcephaly, axial hypotonia, oromotor dysfunction with drooling, joint contractures, and spastic paraplegia resulting in walking difficulties. Some patients may develop seizures; nonspecific dysmorphic features have also been reported (summary by Hengel et al., 2018 and Ouyang et al., 2019). [from OMIM]

Clinical features

From HPO
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Posteriorly rotated ears
MedGen UID:
96566
Concept ID:
C0431478
Congenital Abnormality
A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front).
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
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.
Encephalopathy
MedGen UID:
39314
Concept ID:
C0085584
Disease or Syndrome
Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
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.
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.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Generalized non-motor (absence) seizure
MedGen UID:
1385688
Concept ID:
C4316903
Disease or Syndrome
A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterized by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
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.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Secondary microcephaly
MedGen UID:
608952
Concept ID:
C0431352
Finding
Head circumference which falls below 2 standard deviations below the mean for age and gender because of insufficient head growth after birth.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Drooling
MedGen UID:
8484
Concept ID:
C0013132
Finding
Habitual flow of saliva out of the mouth.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Narrow forehead
MedGen UID:
326956
Concept ID:
C1839758
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations below the mean (objective); or apparently narrow intertemporal region (subjective).
Hypotelorism
MedGen UID:
96107
Concept ID:
C0424711
Finding
Interpupillary distance less than 2 SD below the mean (alternatively, the appearance of an decreased interpupillary distance or closely spaced eyes).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVGlutamate pyruvate transaminase 2 deficiency

Professional guidelines

PubMed

Jiang H, Zheng H
Biosci Rep 2019 Jul 31;39(7) Epub 2019 Jul 5 doi: 10.1042/BSR20182371. PMID: 31189741Free PMC Article
Nomura F, Itoga S, Tamura M, Harada S, Iizuka Y, Nakai T
Alcohol Clin Exp Res 2000 Apr;24(4 Suppl):30S-33S. PMID: 10803776
Sveger T, Thelin T
Acta Paediatr Scand 1981 Mar;70(2):171-7. doi: 10.1111/j.1651-2227.1981.tb05537.x. PMID: 6972148

Recent clinical studies

Etiology

Winrich EJ, Gala KS, Rajhans A, Rios-Perez CD, Royer AJ, Zamani Z, Parthasarathy R, Marsano-Obando LS, Barve AJ, Schwandt ML, Vatsalya V
Int J Mol Sci 2022 Sep 26;23(19) doi: 10.3390/ijms231911332. PMID: 36232646Free PMC Article
Visser ME, Durao S, Sinclair D, Irlam JH, Siegfried N
Cochrane Database Syst Rev 2017 May 18;5(5):CD003650. doi: 10.1002/14651858.CD003650.pub4. PMID: 28518221Free PMC Article
Brown RJ, Meehan CA, Cochran E, Rother KI, Kleiner DE, Walter M, Gorden P
J Clin Endocrinol Metab 2017 May 1;102(5):1511-1519. doi: 10.1210/jc.2016-3628. PMID: 28324110Free PMC Article
Niemelä O
Int J Environ Res Public Health 2016 Jan 27;13(2):166. doi: 10.3390/ijerph13020166. PMID: 26828506Free PMC Article
Yki-Järvinen H, Westerbacka J
Curr Mol Med 2005 May;5(3):287-95. doi: 10.2174/1566524053766031. PMID: 15892648

Diagnosis

Balwani M, Balistreri W, D'Antiga L, Evans J, Ros E, Abel F, Wilson DP
Liver Int 2023 Jul;43(7):1537-1547. Epub 2023 May 24 doi: 10.1111/liv.15620. PMID: 37222260
Benevides GN, Miura IK, Person NC, Pugliese RPS, Danesi VLB, Lima FR, Porta G
J Pediatr (Rio J) 2019 Sep-Oct;95(5):552-558. Epub 2018 Jul 3 doi: 10.1016/j.jped.2018.05.016. PMID: 31340901
Niemelä O
Int J Environ Res Public Health 2016 Jan 27;13(2):166. doi: 10.3390/ijerph13020166. PMID: 26828506Free PMC Article
Yki-Järvinen H, Westerbacka J
Curr Mol Med 2005 May;5(3):287-95. doi: 10.2174/1566524053766031. PMID: 15892648
Simell O, Perheentupa J, Rapola J, Visakorpi JK, Eskelin LE
Am J Med 1975 Aug;59(2):229-40. doi: 10.1016/0002-9343(75)90358-7. PMID: 1155480

Therapy

Balwani M, Balistreri W, D'Antiga L, Evans J, Ros E, Abel F, Wilson DP
Liver Int 2023 Jul;43(7):1537-1547. Epub 2023 May 24 doi: 10.1111/liv.15620. PMID: 37222260
Zhou Z, Lin Y, Gao L, Yang Z, Wang S, Wu B
Toxicol Lett 2019 Oct 1;313:188-195. Epub 2019 Jul 5 doi: 10.1016/j.toxlet.2019.07.007. PMID: 31284022
Visser ME, Durao S, Sinclair D, Irlam JH, Siegfried N
Cochrane Database Syst Rev 2017 May 18;5(5):CD003650. doi: 10.1002/14651858.CD003650.pub4. PMID: 28518221Free PMC Article
Matsumoto M, Hada N, Sakamaki Y, Uno A, Shiga T, Tanaka C, Ito T, Katsume A, Sudoh M
Int J Exp Pathol 2013 Apr;94(2):93-103. Epub 2013 Jan 11 doi: 10.1111/iep.12008. PMID: 23305254Free PMC Article
Simell O, Perheentupa J, Rapola J, Visakorpi JK, Eskelin LE
Am J Med 1975 Aug;59(2):229-40. doi: 10.1016/0002-9343(75)90358-7. PMID: 1155480

Prognosis

Winrich EJ, Gala KS, Rajhans A, Rios-Perez CD, Royer AJ, Zamani Z, Parthasarathy R, Marsano-Obando LS, Barve AJ, Schwandt ML, Vatsalya V
Int J Mol Sci 2022 Sep 26;23(19) doi: 10.3390/ijms231911332. PMID: 36232646Free PMC Article
Hu XL, Li MP, Song PY, Tang J, Chen XP
J Mol Cell Cardiol 2017 Dec;113:33-38. Epub 2017 Sep 29 doi: 10.1016/j.yjmcc.2017.09.010. PMID: 28970090
Visser ME, Durao S, Sinclair D, Irlam JH, Siegfried N
Cochrane Database Syst Rev 2017 May 18;5(5):CD003650. doi: 10.1002/14651858.CD003650.pub4. PMID: 28518221Free PMC Article
Niemelä O
Int J Environ Res Public Health 2016 Jan 27;13(2):166. doi: 10.3390/ijerph13020166. PMID: 26828506Free PMC Article
Yki-Järvinen H, Westerbacka J
Curr Mol Med 2005 May;5(3):287-95. doi: 10.2174/1566524053766031. PMID: 15892648

Clinical prediction guides

Balwani M, Balistreri W, D'Antiga L, Evans J, Ros E, Abel F, Wilson DP
Liver Int 2023 Jul;43(7):1537-1547. Epub 2023 May 24 doi: 10.1111/liv.15620. PMID: 37222260
Baytas O, Kauer JA, Morrow EM
Neurobiol Dis 2022 Oct 15;173:105831. Epub 2022 Jul 28 doi: 10.1016/j.nbd.2022.105831. PMID: 35908744Free PMC Article
Hu XL, Li MP, Song PY, Tang J, Chen XP
J Mol Cell Cardiol 2017 Dec;113:33-38. Epub 2017 Sep 29 doi: 10.1016/j.yjmcc.2017.09.010. PMID: 28970090
Matsumoto M, Hada N, Sakamaki Y, Uno A, Shiga T, Tanaka C, Ito T, Katsume A, Sudoh M
Int J Exp Pathol 2013 Apr;94(2):93-103. Epub 2013 Jan 11 doi: 10.1111/iep.12008. PMID: 23305254Free PMC Article
Yki-Järvinen H, Westerbacka J
Curr Mol Med 2005 May;5(3):287-95. doi: 10.2174/1566524053766031. PMID: 15892648

Recent systematic reviews

Heerfordt IM, Lerche CM, Philipsen PA, Wulf HC
Photodiagnosis Photodyn Ther 2024 Jun;47:104211. Epub 2024 May 9 doi: 10.1016/j.pdpdt.2024.104211. PMID: 38734198
Mubder M, Azab M, Jayaraj M, Cross C, Lankarani D, Dhindsa B, Pan JJ, Ohning G
Medicine (Baltimore) 2019 Sep;98(37):e17094. doi: 10.1097/MD.0000000000017094. PMID: 31517833Free PMC Article
Visser ME, Durao S, Sinclair D, Irlam JH, Siegfried N
Cochrane Database Syst Rev 2017 May 18;5(5):CD003650. doi: 10.1002/14651858.CD003650.pub4. PMID: 28518221Free PMC Article
Dai YJ, Sun LL, Li MY, Ding CL, Su YC, Sun LJ, Xue SH, Yan F, Zhao CH, Wang W
Adv Nutr 2016 Mar;7(2):279-86. Epub 2016 Mar 15 doi: 10.3945/an.114.007427. PMID: 26980811Free PMC Article

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