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Atypical glycine encephalopathy

MedGen UID:
934910
Concept ID:
C4310943
Disease or Syndrome
Synonym: Glycine encephalopathy with normal serum glycine
Modes of inheritance:
Unknown inheritance
MedGen UID:
989040
Concept ID:
CN307042
Finding
Source: Orphanet
Hereditary clinical entity whose mode of inheritance is unknown.
 
Gene (location): SLC6A9 (1p34.1)
 
Monarch Initiative: MONDO:0015010
OMIM®: 617301
Orphanet: ORPHA289863

Disease characteristics

Excerpted from the GeneReview: GLYT1 Encephalopathy
GLYT1 encephalopathy is characterized in neonates by severe hypotonia, respiratory failure requiring mechanical ventilation, and absent neonatal reflexes; encephalopathy, including impaired consciousness and unresponsiveness, may be present. Arthrogryposis or joint laxity can be observed. Generalized hypotonia develops later into axial hypotonia with limb hypertonicity and a startle-like response to vocal and visual stimuli which should not be confused with seizures. To date, three of the six affected children reported from three families died between ages two days and seven months; the oldest reported living child is severely globally impaired at age three years. Because of the limited number of affected individuals reported to date, the phenotype has not yet been completely described. [from GeneReviews]
Authors:
Alina Kurolap  |  Tova Hershkovitz  |  Hagit N Baris   view full author information

Additional description

From OMIM
Glycine encephalopathy with normal serum glycine is a severe metabolic disorder characterized by arthrogryposis multiplex congenita, joint hyperlaxity, lack of neonatal respiratory effort, axial hypotonia, hypertonia with pronounced clonus, and delayed psychomotor development. Some patients may have dysmorphic facial features and/or brain imaging abnormalities. Laboratory studies show increased CSF glycine and normal or only mildly increased serum glycine. Most patients die in infancy. The disorder is similar to, but distinct from, glycine encephalopathy (GCE; 605899) due to mutations in genes encoding the glycine cleavage system (summary by Kurolap et al., 2016).  http://www.omim.org/entry/617301

Clinical features

From HPO
Clubfoot
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Hand clenching
MedGen UID:
65994
Concept ID:
C0239815
Finding
An abnormal hand posture in which the hands are clenched to fists. All digits held completely flexed at the metacarpophalangeal and interphalangeal joints. In prenatal sonography of the fetal clenched hand, the index finger overlaps a clenched fist formed by the other digits. The proximal interphalangeal articulation of the index finger is flexed and ulnarly deviated, and the thumb is adducted.
Genu recurvatum
MedGen UID:
107486
Concept ID:
C0546964
Anatomical Abnormality
An abnormally increased extension of the knee joint, so that the knee can bend backwards.
Overlapping toe
MedGen UID:
182531
Concept ID:
C0920299
Anatomical Abnormality
Describes a foot digit resting on the dorsal surface of an adjacent digit when the foot is at rest. Initially clawing may be dynamic and only noticeable on walking. Over time the plantar plate tears, subluxation occurs at the metatarsophalangeal joint (MTPJ), and the deformity becomes permanent.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
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.
Clonus
MedGen UID:
40341
Concept ID:
C0009024
Sign or Symptom
A series of rhythmic and involuntary muscle contractions (at a frequency of about 5 to 7 Hz) that occur in response to an abruptly applied and sustained stretch.
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.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
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.
Exaggerated startle response
MedGen UID:
329357
Concept ID:
C1740801
Finding
An exaggerated startle reaction in response to a sudden unexpected visual or acoustic stimulus, or a quick movement near the face.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Hip dislocation
MedGen UID:
42455
Concept ID:
C0019554
Injury or Poisoning
Displacement of the femur from its normal location in the hip joint.
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.
Retrognathia
MedGen UID:
19766
Concept ID:
C0035353
Congenital Abnormality
An abnormality in which the mandible is mislocalised posteriorly.
Dolichocephaly
MedGen UID:
65142
Concept ID:
C0221358
Congenital Abnormality
An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture.
Trigonocephaly
MedGen UID:
82713
Concept ID:
C0265535
Congenital Abnormality
Wedge-shaped, or triangular head, with the apex of the triangle at the midline of the forehead and the base of the triangle at the occiput.
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.
Elbow flexion contracture
MedGen UID:
98367
Concept ID:
C0409338
Acquired Abnormality
An elbow contracture that limits the ability of the elbow joint to be extended (straightened), meaning that the elbow is fixed in an flexed (bent) position.
Hip contracture
MedGen UID:
140815
Concept ID:
C0409354
Acquired Abnormality
Lack of full passive range of motion (restrictions in flexion, extension, or other movements) of the hip joint resulting from structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules and/or skin.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Arthrogryposis multiplex congenita
MedGen UID:
1830310
Concept ID:
C5779613
Disease or Syndrome
Multiple congenital contractures in different body areas.
Apnea
MedGen UID:
2009
Concept ID:
C0003578
Sign or Symptom
Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.
Respiratory failure
MedGen UID:
257837
Concept ID:
C1145670
Disease or Syndrome
A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits.
Myopathic facies
MedGen UID:
90695
Concept ID:
C0332615
Finding
A facial appearance characteristic of myopathic conditions. The face appears expressionless with sunken cheeks, bilateral ptosis, and inability to elevate the corners of the mouth, due to muscle weakness.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Long eyelashes
MedGen UID:
342955
Concept ID:
C1853738
Finding
Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective).
Fetal distress
MedGen UID:
5164
Concept ID:
C0015930
Pathologic Function
An intrauterine state characterized by suboptimal values in the fetal heart rate, oxygenation of fetal blood, or other parameters indicative of compromise of the fetus. Signs of fetal distress include repetitive variable decelerations, fetal tachycardia or bradycardia, late decelerations, or low biophysical profile.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAtypical glycine encephalopathy

Professional guidelines

PubMed

Deutsch SI, Rosse RB, Mastropaolo J
Clin Neuropharmacol 1998 Mar-Apr;21(2):71-9. PMID: 9579291

Recent clinical studies

Etiology

Tekturk P, Baykan B, Erdag E, Peach S, Sezgin M, Yapici Z, Küçükali Cİ, Vincent A, Tuzun E
Brain Dev 2018 Nov;40(10):909-917. Epub 2018 Jun 21 doi: 10.1016/j.braindev.2018.06.002. PMID: 29935963
Gillinder L, Tjoa L, Mantzioris B, Blum S, Dionisio S
Epileptic Disord 2017 Dec 1;19(4):439-449. doi: 10.1684/epd.2017.0946. PMID: 29258968

Diagnosis

Lee WT
Brain Dev 2011 Oct;33(9):745-52. Epub 2011 Jul 30 doi: 10.1016/j.braindev.2011.06.014. PMID: 21803516
Kure S
Brain Dev 2011 Oct;33(9):753-7. Epub 2011 Apr 5 doi: 10.1016/j.braindev.2011.03.001. PMID: 21470805
Kure S, Korman SH, Kanno J, Narisawa A, Kubota M, Takayanagi T, Takayanagi M, Saito T, Matsui A, Kamada F, Aoki Y, Ohura T, Matsubara Y
Ann Neurol 2006 May;59(5):862-7. doi: 10.1002/ana.20853. PMID: 16634033
Dinopoulos A, Matsubara Y, Kure S
Mol Genet Metab 2005 Sep-Oct;86(1-2):61-9. doi: 10.1016/j.ymgme.2005.07.016. PMID: 16157495
Applegarth DA, Toone JR
Mol Genet Metab 2001 Sep-Oct;74(1-2):139-46. doi: 10.1006/mgme.2001.3224. PMID: 11592811

Therapy

Ude C, Ambegaonkar G
BMJ Case Rep 2016 Oct 19;2016 doi: 10.1136/bcr-2016-216468. PMID: 27797796Free PMC Article
Morrison PF, Sankar R, Shields WD
Pediatr Neurol 2006 Nov;35(5):356-8. doi: 10.1016/j.pediatrneurol.2006.06.009. PMID: 17074608
Neuberger JM, Schweitzer S, Rolland MO, Burghard R
J Inherit Metab Dis 2000 Feb;23(1):22-6. doi: 10.1023/a:1005642728513. PMID: 10682305
Deutsch SI, Rosse RB, Mastropaolo J
Clin Neuropharmacol 1998 Mar-Apr;21(2):71-9. PMID: 9579291

Prognosis

Poothrikovil RP, Al Thihli K, Al Futaisi A, Al Murshidi F
Neurodiagn J 2019;59(3):142-151. Epub 2019 Aug 21 doi: 10.1080/21646821.2019.1645549. PMID: 31433733
Tekturk P, Baykan B, Erdag E, Peach S, Sezgin M, Yapici Z, Küçükali Cİ, Vincent A, Tuzun E
Brain Dev 2018 Nov;40(10):909-917. Epub 2018 Jun 21 doi: 10.1016/j.braindev.2018.06.002. PMID: 29935963
Lee WT
Brain Dev 2011 Oct;33(9):745-52. Epub 2011 Jul 30 doi: 10.1016/j.braindev.2011.06.014. PMID: 21803516
Pardal-Fernández JM, Carrascosa-Romero MC, de Cabo-de la Vega C, Iniesta-López I, Gil-Pons E, Martínez-Gutiérrez A
Epileptic Disord 2009 Mar;11(1):48-53. Epub 2009 Mar 20 doi: 10.1684/epd.2009.0249. PMID: 19299230
Dinopoulos A, Matsubara Y, Kure S
Mol Genet Metab 2005 Sep-Oct;86(1-2):61-9. doi: 10.1016/j.ymgme.2005.07.016. PMID: 16157495

Clinical prediction guides

Yoshikawa A, Nishimura F, Inai A, Eriguchi Y, Nishioka M, Takaya A, Tochigi M, Kawamura Y, Umekage T, Kato K, Sasaki T, Ohashi Y, Iwamoto K, Kasai K, Kakiuchi C
Psychiatry Clin Neurosci 2018 Mar;72(3):168-179. Epub 2018 Jan 31 doi: 10.1111/pcn.12628. PMID: 29232014
Dinopoulos A, Matsubara Y, Kure S
Mol Genet Metab 2005 Sep-Oct;86(1-2):61-9. doi: 10.1016/j.ymgme.2005.07.016. PMID: 16157495

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