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Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities(NELABA; LIPT2D)

MedGen UID:
1624694
Concept ID:
C4540052
Disease or Syndrome
Synonym: LIPOYLTRANSFERASE 2 DEFICIENCY
 
Gene (location): LIPT2 (11q13.4)
 
Monarch Initiative: MONDO:0060562
OMIM®: 617668

Definition

NELABA is a severe autosomal recessive metabolic disorder characterized by onset at birth of progressive encephalopathy associated with increased serum lactate. Affected individuals have little or no psychomotor development and show brain abnormalities, including cerebral atrophy, cysts, and white matter abnormalities. Some patients die in infancy (summary by Habarou et al., 2017). [from OMIM]

Clinical features

From HPO
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.
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.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised 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.
EEG abnormality
MedGen UID:
56235
Concept ID:
C0151611
Finding
Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp.
Spastic tetraparesis
MedGen UID:
658719
Concept ID:
C0575059
Disease or Syndrome
Spastic weakness affecting all four limbs.
Abnormal cerebral white matter morphology
MedGen UID:
181756
Concept ID:
C0948163
Pathologic Function
An abnormality of the cerebral white matter.
Periventricular cysts
MedGen UID:
326980
Concept ID:
C1839858
Finding
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Lateral ventricle dilatation
MedGen UID:
383904
Concept ID:
C1856409
Pathologic Function
Simplified gyral pattern
MedGen UID:
413664
Concept ID:
C2749675
Finding
An abnormality of the cerebral cortex with fewer gyri but with normal cortical thickness. This pattern is usually often associated with congenital microcephaly.
Profound global developmental delay
MedGen UID:
766364
Concept ID:
C3553450
Disease or Syndrome
A profound delay in the achievement of motor or mental milestones in the domains of development of a child.
Delayed CNS myelination
MedGen UID:
867393
Concept ID:
C4021758
Anatomical Abnormality
Delayed myelination in the central nervous system.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
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.
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.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Lactic acidosis
MedGen UID:
1717
Concept ID:
C0001125
Disease or Syndrome
An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.
Hyper-beta-alaninemia
MedGen UID:
75702
Concept ID:
C0268630
Disease or Syndrome
An increased concentration of alanine in the blood.
Increased serum pyruvate
MedGen UID:
376596
Concept ID:
C1849488
Finding
An increased concentration of pyruvate in the blood.

Professional guidelines

PubMed

DeBrosse SD, Okajima K, Zhang S, Nakouzi G, Schmotzer CL, Lusk-Kopp M, Frohnapfel MB, Grahame G, Kerr DS
Mol Genet Metab 2012 Nov;107(3):394-402. Epub 2012 Sep 7 doi: 10.1016/j.ymgme.2012.09.001. PMID: 23021068

Recent clinical studies

Etiology

Azzopardi D, Robertson NJ, Bainbridge A, Cady E, Charles-Edwards G, Deierl A, Fagiolo G, Franks NP, Griffiths J, Hajnal J, Juszczak E, Kapetanakis B, Linsell L, Maze M, Omar O, Strohm B, Tusor N, Edwards AD
Lancet Neurol 2016 Feb;15(2):145-153. Epub 2015 Dec 19 doi: 10.1016/S1474-4422(15)00347-6. PMID: 26708675Free PMC Article
DeBrosse SD, Okajima K, Zhang S, Nakouzi G, Schmotzer CL, Lusk-Kopp M, Frohnapfel MB, Grahame G, Kerr DS
Mol Genet Metab 2012 Nov;107(3):394-402. Epub 2012 Sep 7 doi: 10.1016/j.ymgme.2012.09.001. PMID: 23021068
Barnerias C, Saudubray JM, Touati G, De Lonlay P, Dulac O, Ponsot G, Marsac C, Brivet M, Desguerre I
Dev Med Child Neurol 2010 Feb;52(2):e1-9. Epub 2009 Dec 1 doi: 10.1111/j.1469-8749.2009.03541.x. PMID: 20002125
Murray DM, Boylan GB, Fitzgerald AP, Ryan CA, Murphy BP, Connolly S
Arch Dis Child Fetal Neonatal Ed 2008 May;93(3):F183-6. Epub 2006 Nov 28 doi: 10.1136/adc.2006.100800. PMID: 17132680
García-Cazorla A, Rabier D, Touati G, Chadefaux-Vekemans B, Marsac C, de Lonlay P, Saudubray JM
Ann Neurol 2006 Jan;59(1):121-7. doi: 10.1002/ana.20709. PMID: 16278852

Diagnosis

Saini N, Vijayasree V, Nandury EC, Dalal A, Aggarwal S
Prenat Diagn 2022 Dec;42(13):1682-1685. Epub 2022 Nov 26 doi: 10.1002/pd.6272. PMID: 36411461
Forny P, Hochuli M, Rahman Y, Deheragoda M, Weber A, Baruteau J, Grunewald S
J Inherit Metab Dis 2019 Sep;42(5):793-802. Epub 2019 Jul 17 doi: 10.1002/jimd.12143. PMID: 31260114
De Meirleir L
Handb Clin Neurol 2013;113:1667-73. doi: 10.1016/B978-0-444-59565-2.00034-4. PMID: 23622387
Morel AS, Joris N, Meuli R, Jacquemont S, Ballhausen D, Bonafé L, Fattet S, Tolsa JF
Eur J Pediatr 2009 Mar;168(3):311-5. Epub 2008 Jun 14 doi: 10.1007/s00431-008-0756-4. PMID: 18553104
Murray DM, Boylan GB, Fitzgerald AP, Ryan CA, Murphy BP, Connolly S
Arch Dis Child Fetal Neonatal Ed 2008 May;93(3):F183-6. Epub 2006 Nov 28 doi: 10.1136/adc.2006.100800. PMID: 17132680

Therapy

Azzopardi D, Robertson NJ, Bainbridge A, Cady E, Charles-Edwards G, Deierl A, Fagiolo G, Franks NP, Griffiths J, Hajnal J, Juszczak E, Kapetanakis B, Linsell L, Maze M, Omar O, Strohm B, Tusor N, Edwards AD
Lancet Neurol 2016 Feb;15(2):145-153. Epub 2015 Dec 19 doi: 10.1016/S1474-4422(15)00347-6. PMID: 26708675Free PMC Article
Barnerias C, Saudubray JM, Touati G, De Lonlay P, Dulac O, Ponsot G, Marsac C, Brivet M, Desguerre I
Dev Med Child Neurol 2010 Feb;52(2):e1-9. Epub 2009 Dec 1 doi: 10.1111/j.1469-8749.2009.03541.x. PMID: 20002125
Mochel F, DeLonlay P, Touati G, Brunengraber H, Kinman RP, Rabier D, Roe CR, Saudubray JM
Mol Genet Metab 2005 Apr;84(4):305-12. doi: 10.1016/j.ymgme.2004.09.007. PMID: 15781190

Prognosis

Forny P, Hochuli M, Rahman Y, Deheragoda M, Weber A, Baruteau J, Grunewald S
J Inherit Metab Dis 2019 Sep;42(5):793-802. Epub 2019 Jul 17 doi: 10.1002/jimd.12143. PMID: 31260114
Smith AC, Ito Y, Ahmed A, Schwartzentruber JA, Beaulieu CL, Aberg E, Majewski J, Bulman DE, Horsting-Wethly K, Koning DV; Care4Rare Canada Consortium, Rodenburg RJ, Boycott KM, Penney LS
J Inherit Metab Dis 2018 Jul;41(4):719-729. Epub 2018 Mar 20 doi: 10.1007/s10545-017-0122-7. PMID: 29560582
Baertling F, Haack TB, Rodenburg RJ, Schaper J, Seibt A, Strom TM, Meitinger T, Mayatepek E, Hadzik B, Selcan G, Prokisch H, Distelmaier F
Neurogenetics 2015 Jul;16(3):237-40. Epub 2015 Feb 10 doi: 10.1007/s10048-015-0440-6. PMID: 25663021
Morel AS, Joris N, Meuli R, Jacquemont S, Ballhausen D, Bonafé L, Fattet S, Tolsa JF
Eur J Pediatr 2009 Mar;168(3):311-5. Epub 2008 Jun 14 doi: 10.1007/s00431-008-0756-4. PMID: 18553104
Murray DM, Boylan GB, Fitzgerald AP, Ryan CA, Murphy BP, Connolly S
Arch Dis Child Fetal Neonatal Ed 2008 May;93(3):F183-6. Epub 2006 Nov 28 doi: 10.1136/adc.2006.100800. PMID: 17132680

Clinical prediction guides

Sabouny R, Wong R, Lee-Glover L, Greenway SC, Sinasac DS; Care4Rare Canada, Khan A, Shutt TE
Biochim Biophys Acta Mol Basis Dis 2019 Nov 1;1865(11):165536. Epub 2019 Aug 20 doi: 10.1016/j.bbadis.2019.165536. PMID: 31442532
Smith AC, Ito Y, Ahmed A, Schwartzentruber JA, Beaulieu CL, Aberg E, Majewski J, Bulman DE, Horsting-Wethly K, Koning DV; Care4Rare Canada Consortium, Rodenburg RJ, Boycott KM, Penney LS
J Inherit Metab Dis 2018 Jul;41(4):719-729. Epub 2018 Mar 20 doi: 10.1007/s10545-017-0122-7. PMID: 29560582
Murray DM, Boylan GB, Fitzgerald AP, Ryan CA, Murphy BP, Connolly S
Arch Dis Child Fetal Neonatal Ed 2008 May;93(3):F183-6. Epub 2006 Nov 28 doi: 10.1136/adc.2006.100800. PMID: 17132680
Valente L, Tiranti V, Marsano RM, Malfatti E, Fernandez-Vizarra E, Donnini C, Mereghetti P, De Gioia L, Burlina A, Castellan C, Comi GP, Savasta S, Ferrero I, Zeviani M
Am J Hum Genet 2007 Jan;80(1):44-58. Epub 2006 Nov 15 doi: 10.1086/510559. PMID: 17160893Free PMC Article
García-Cazorla A, Rabier D, Touati G, Chadefaux-Vekemans B, Marsac C, de Lonlay P, Saudubray JM
Ann Neurol 2006 Jan;59(1):121-7. doi: 10.1002/ana.20709. PMID: 16278852

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