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Maternally-inherited Leigh syndrome

MedGen UID:: 443976
•Concept ID:: C2931092
•: Disease or Syndrome

Synonyms:	Leigh disease, maternally inherited; Subacute necrotizing encephalomyelopathy maternally inherited
SNOMED CT:	Maternally inherited Leigh syndrome (717052002); Maternally inherited Leigh disease (717052002); Maternally inherited infantile subacute necrotizing encephalopathy (717052002)
Modes of inheritance:	Mitochondrial inheritance MedGen UID: 165802 •Concept ID: C0887941 • Genetic Function Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on the mitochondrial genome. Because the mitochondrial genome is essentially always maternally inherited, a mitochondrial condition can only be transmitted by females, although the condition can affect both sexes. The proportion of mutant mitochondria can vary (heteroplasmy). Mitochondrial inheritance (Orphanet)

Monarch Initiative:	MONDO:0016814
Orphanet:	ORPHA255210

Definition

A rare subtype of Leigh syndrome with clinical characteristics of encephalopathy, lactic acidosis, seizures, cardiomyopathy, respiratory disorders and developmental delay. Onset in infancy or early childhood resulting from maternally-inherited mutations in mitochondrial DNA. [from SNOMEDCT_US]

Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVHereditary hearing loss and deafness

Congenital, Hereditary, and Neonatal Diseases and Abnormalities
- Inborn genetic diseases
  - Inborn errors of metabolism
    - Brain Diseases, Metabolic, Inborn
      - Leigh syndrome
        Maternally-inherited Leigh syndrome

Follow this link to review classifications for Maternally-inherited Leigh syndrome in Orphanet.

Recent clinical studies

Etiology

3697G>A in MT-ND1 is a causative mutation in mitochondrial disease.

Spangenberg L, Graña M, Greif G, Suarez-Rivero JM, Krysztal K, Tapié A, Boidi M, Fraga V, Lemes A, Gueçaimburú R, Cerisola A, Sánchez-Alcázar JA, Robello C, Raggio V, Naya H
Mitochondrion 2016 May;28:54-9. Epub 2016 Mar 24 doi: 10.1016/j.mito.2016.03.006. PMID: 27017994

Low citrulline in Leigh disease: still a biomarker of maternally inherited Leigh syndrome.

Debray FG, Lambert M, Allard P, Mitchell GA
J Child Neurol 2010 Aug;25(8):1000-2. Epub 2010 May 14 doi: 10.1177/0883073809351983. PMID: 20472868

Long-term outcome of Leigh syndrome caused by the NARP-T8993C mtDNA mutation.

Debray FG, Lambert M, Lortie A, Vanasse M, Mitchell GA
Am J Med Genet A 2007 Sep 1;143A(17):2046-51. doi: 10.1002/ajmg.a.31880. PMID: 17663470

Maternally-inherited Leigh syndrome-related mutations bolster mitochondrial-mediated apoptosis.

Carrozzo R, Rizza T, Stringaro A, Pierini R, Mormone E, Santorelli FM, Malorni W, Matarrese P
J Neurochem 2004 Jul;90(2):490-501. doi: 10.1111/j.1471-4159.2004.02505.x. PMID: 15228605

See all (4)

Diagnosis

Novel insights into the functional metabolic impact of an apparent de novo m.8993T>G variant in the MT-ATP6 gene associated with maternally inherited form of Leigh Syndrome.

Uittenbogaard M, Brantner CA, Fang Z, Wong LC, Gropman A, Chiaramello A
Mol Genet Metab 2018 May;124(1):71-81. Epub 2018 Mar 27 doi: 10.1016/j.ymgme.2018.03.011. PMID: 29602698 Free PMC Article

Low citrulline in Leigh disease: still a biomarker of maternally inherited Leigh syndrome.

Debray FG, Lambert M, Allard P, Mitchell GA
J Child Neurol 2010 Aug;25(8):1000-2. Epub 2010 May 14 doi: 10.1177/0883073809351983. PMID: 20472868

Maternally inherited Leigh syndrome: an unusual cause of infantile apnea.

Shuk-kuen Chau C, Kwok KL, Ng DK, Lam CW, Tong SF, Chan YW, Siu WK, Yuen YP
Sleep Breath 2010 Jun;14(2):161-5. Epub 2009 Aug 11 doi: 10.1007/s11325-009-0288-9. PMID: 19669818

Genetic, pathogenetic, and phenotypic implications of the mitochondrial A3243G tRNALeu(UUR) mutation.

Finsterer J
Acta Neurol Scand 2007 Jul;116(1):1-14. doi: 10.1111/j.1600-0404.2007.00836.x. PMID: 17587249

Maternally inherited Leigh syndrome.

Ciafaloni E, Santorelli FM, Shanske S, Deonna T, Roulet E, Janzer C, Pescia G, DiMauro S
J Pediatr 1993 Mar;122(3):419-22. doi: 10.1016/s0022-3476(05)83431-6. PMID: 8095070

See all (11)

Therapy

3697G>A in MT-ND1 is a causative mutation in mitochondrial disease.

See all (1)

Prognosis

Leigh disease presenting in utero due to a novel missense mutation in the mitochondrial DNA-ND3.

Leshinsky-Silver E, Lev D, Malinger G, Shapira D, Cohen S, Lerman-Sagie T, Saada A
Mol Genet Metab 2010 May;100(1):65-70. Epub 2010 Feb 10 doi: 10.1016/j.ymgme.2010.02.002. PMID: 20202874

Long-term outcome of Leigh syndrome caused by the NARP-T8993C mtDNA mutation.

Debray FG, Lambert M, Lortie A, Vanasse M, Mitchell GA
Am J Med Genet A 2007 Sep 1;143A(17):2046-51. doi: 10.1002/ajmg.a.31880. PMID: 17663470

G8363A mutation in the mitochondrial DNA transfer ribonucleic acidLys gene: another cause of Leigh syndrome.

Shtilbans A, Shanske S, Goodman S, Sue CM, Bruno C, Johnson TL, Lava NS, Waheed N, DiMauro S
J Child Neurol 2000 Nov;15(11):759-61. doi: 10.1177/088307380001501109. PMID: 11108511

Clinical heterogeneity associated with the mitochondrial DNA T8993C point mutation.

Santorelli FM, Mak SC, Vazquez-Memije ME, Shanske S, Kranz-Eble P, Jain KD, Bluestone DL, De Vivo DC, DiMauro S
Pediatr Res 1996 May;39(5):914-7. doi: 10.1203/00006450-199605000-00028. PMID: 8726250

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Clinical prediction guides

Epilepsy in MT-ATP6 - related mils/NARP: correlation of elettroclinical features with heteroplasmy.

Licchetta L, Ferri L, La Morgia C, Zenesini C, Caporali L, Lucia Valentino M, Minardi R, Fulitano D, Di Vito L, Mostacci B, Alvisi L, Avoni P, Liguori R, Tinuper P, Bisulli F, Carelli V
Ann Clin Transl Neurol 2021 Mar;8(3):704-710. Epub 2021 Jan 21 doi: 10.1002/acn3.51259. PMID: 33476484 Free PMC Article

Biochemical consequences in yeast of the human mitochondrial DNA 8993T>C mutation in the ATPase6 gene found in NARP/MILS patients.

Kucharczyk R, Rak M, di Rago JP
Biochim Biophys Acta 2009 May;1793(5):817-24. Epub 2009 Mar 6 doi: 10.1016/j.bbamcr.2009.02.011. PMID: 19269308

Long-term outcome of Leigh syndrome caused by the NARP-T8993C mtDNA mutation.

Debray FG, Lambert M, Lortie A, Vanasse M, Mitchell GA
Am J Med Genet A 2007 Sep 1;143A(17):2046-51. doi: 10.1002/ajmg.a.31880. PMID: 17663470

ATP6 homoplasmic mutations inhibit and destabilize the human F1F0-ATP synthase without preventing enzyme assembly and oligomerization.

Cortés-Hernández P, Vázquez-Memije ME, García JJ
J Biol Chem 2007 Jan 12;282(2):1051-8. Epub 2006 Nov 22 doi: 10.1074/jbc.M606828200. PMID: 17121862

See all (4)