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Leber plus disease

MedGen UID:
930394
Concept ID:
C4304725
Disease or Syndrome
Synonym: LHON plus disease
SNOMED CT: Leber plus disease (719430008)
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).
 
Monarch Initiative: MONDO:0020478
Orphanet: ORPHA99718

Definition

Leber plus disease describes patients with the clinical features of Leber''s hereditary optic neuropathy in combination with other serious systemic or neurological abnormalities. These abnormalities include: postural tremor, motor disorder, multiple sclerosis-like syndrome, spinal cord disease, skeletal changes, Parkinsonism with dystonia, anarthria, dystonia, motor and sensory peripheral neuropathy, spasticity and mild encephalopathy. It is caused by maternally inherited mitochondrial DNA (mtDNA) mutations. [from SNOMEDCT_US]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • Leber plus disease

Professional guidelines

PubMed

Tubau-Juni N, Bassaganya-Riera J, Leber AJ, Alva SS, Hontecillas R
Inflamm Bowel Dis 2024 Jan 5;30(1):103-113. doi: 10.1093/ibd/izad124. PMID: 37436905
Thorburn DR, Dahl HH
Am J Med Genet 2001 Spring;106(1):102-14. doi: 10.1002/ajmg.1380. PMID: 11579429

Recent clinical studies

Etiology

Garcia-Manero G, McCloskey J, Griffiths EA, Yee KWL, Zeidan AM, Al-Kali A, Deeg HJ, Patel PA, Sabloff M, Keating MM, Zhu N, Gabrail NY, Fazal S, Maly J, Odenike O, Kantarjian H, DeZern AE, O'Connell CL, Roboz GJ, Busque L, Buckstein R, Amin H, Randhawa J, Leber B, Shastri A, Dao KH, Oganesian A, Hao Y, Keer HN, Azab M, Savona MR
Lancet Haematol 2024 Jan;11(1):e15-e26. doi: 10.1016/S2352-3026(23)00338-1. PMID: 38135371
DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Döhner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hájek R, Porkka K, Illés Á, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW
N Engl J Med 2020 Aug 13;383(7):617-629. doi: 10.1056/NEJMoa2012971. PMID: 32786187
Maron DJ, Hochman JS, Reynolds HR, Bangalore S, O'Brien SM, Boden WE, Chaitman BR, Senior R, López-Sendón J, Alexander KP, Lopes RD, Shaw LJ, Berger JS, Newman JD, Sidhu MS, Goodman SG, Ruzyllo W, Gosselin G, Maggioni AP, White HD, Bhargava B, Min JK, Mancini GBJ, Berman DS, Picard MH, Kwong RY, Ali ZA, Mark DB, Spertus JA, Krishnan MN, Elghamaz A, Moorthy N, Hueb WA, Demkow M, Mavromatis K, Bockeria O, Peteiro J, Miller TD, Szwed H, Doerr R, Keltai M, Selvanayagam JB, Steg PG, Held C, Kohsaka S, Mavromichalis S, Kirby R, Jeffries NO, Harrell FE Jr, Rockhold FW, Broderick S, Ferguson TB Jr, Williams DO, Harrington RA, Stone GW, Rosenberg Y; ISCHEMIA Research Group
N Engl J Med 2020 Apr 9;382(15):1395-1407. Epub 2020 Mar 30 doi: 10.1056/NEJMoa1915922. PMID: 32227755Free PMC Article
Yu-Wai-Man P, Votruba M, Burté F, La Morgia C, Barboni P, Carelli V
Acta Neuropathol 2016 Dec;132(6):789-806. Epub 2016 Sep 30 doi: 10.1007/s00401-016-1625-2. PMID: 27696015Free PMC Article
Tranchant C, Anheim M
Rev Neurol (Paris) 2016 Aug-Sep;172(8-9):524-529. Epub 2016 Jul 28 doi: 10.1016/j.neurol.2016.07.003. PMID: 27476418

Diagnosis

Zibold J, von Livonius B, Kolarova H, Rudolph G, Priglinger CS, Klopstock T, Catarino CB
Orphanet J Rare Dis 2022 Aug 9;17(1):310. doi: 10.1186/s13023-022-02453-z. PMID: 35945620Free PMC Article
Birnbaum FA, Gospe SM 3rd
J Neuroophthalmol 2021 Dec 1;41(4):e715-e717. doi: 10.1097/WNO.0000000000001151. PMID: 33417421
Maron DJ, Hochman JS, Reynolds HR, Bangalore S, O'Brien SM, Boden WE, Chaitman BR, Senior R, López-Sendón J, Alexander KP, Lopes RD, Shaw LJ, Berger JS, Newman JD, Sidhu MS, Goodman SG, Ruzyllo W, Gosselin G, Maggioni AP, White HD, Bhargava B, Min JK, Mancini GBJ, Berman DS, Picard MH, Kwong RY, Ali ZA, Mark DB, Spertus JA, Krishnan MN, Elghamaz A, Moorthy N, Hueb WA, Demkow M, Mavromatis K, Bockeria O, Peteiro J, Miller TD, Szwed H, Doerr R, Keltai M, Selvanayagam JB, Steg PG, Held C, Kohsaka S, Mavromichalis S, Kirby R, Jeffries NO, Harrell FE Jr, Rockhold FW, Broderick S, Ferguson TB Jr, Williams DO, Harrington RA, Stone GW, Rosenberg Y; ISCHEMIA Research Group
N Engl J Med 2020 Apr 9;382(15):1395-1407. Epub 2020 Mar 30 doi: 10.1056/NEJMoa1915922. PMID: 32227755Free PMC Article
Tranchant C, Anheim M
Rev Neurol (Paris) 2016 Aug-Sep;172(8-9):524-529. Epub 2016 Jul 28 doi: 10.1016/j.neurol.2016.07.003. PMID: 27476418
Thorburn DR, Dahl HH
Am J Med Genet 2001 Spring;106(1):102-14. doi: 10.1002/ajmg.1380. PMID: 11579429

Therapy

Garcia-Manero G, McCloskey J, Griffiths EA, Yee KWL, Zeidan AM, Al-Kali A, Deeg HJ, Patel PA, Sabloff M, Keating MM, Zhu N, Gabrail NY, Fazal S, Maly J, Odenike O, Kantarjian H, DeZern AE, O'Connell CL, Roboz GJ, Busque L, Buckstein R, Amin H, Randhawa J, Leber B, Shastri A, Dao KH, Oganesian A, Hao Y, Keer HN, Azab M, Savona MR
Lancet Haematol 2024 Jan;11(1):e15-e26. doi: 10.1016/S2352-3026(23)00338-1. PMID: 38135371
Tubau-Juni N, Bassaganya-Riera J, Leber AJ, Alva SS, Hontecillas R
Inflamm Bowel Dis 2024 Jan 5;30(1):103-113. doi: 10.1093/ibd/izad124. PMID: 37436905
DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Döhner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hájek R, Porkka K, Illés Á, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW
N Engl J Med 2020 Aug 13;383(7):617-629. doi: 10.1056/NEJMoa2012971. PMID: 32786187
Maron DJ, Hochman JS, Reynolds HR, Bangalore S, O'Brien SM, Boden WE, Chaitman BR, Senior R, López-Sendón J, Alexander KP, Lopes RD, Shaw LJ, Berger JS, Newman JD, Sidhu MS, Goodman SG, Ruzyllo W, Gosselin G, Maggioni AP, White HD, Bhargava B, Min JK, Mancini GBJ, Berman DS, Picard MH, Kwong RY, Ali ZA, Mark DB, Spertus JA, Krishnan MN, Elghamaz A, Moorthy N, Hueb WA, Demkow M, Mavromatis K, Bockeria O, Peteiro J, Miller TD, Szwed H, Doerr R, Keltai M, Selvanayagam JB, Steg PG, Held C, Kohsaka S, Mavromichalis S, Kirby R, Jeffries NO, Harrell FE Jr, Rockhold FW, Broderick S, Ferguson TB Jr, Williams DO, Harrington RA, Stone GW, Rosenberg Y; ISCHEMIA Research Group
N Engl J Med 2020 Apr 9;382(15):1395-1407. Epub 2020 Mar 30 doi: 10.1056/NEJMoa1915922. PMID: 32227755Free PMC Article
Zakrzewski H, Modabber M, Wilson N, Al-Hertani W, Toffoli D
J Neuroophthalmol 2019 Jun;39(2):249-252. doi: 10.1097/WNO.0000000000000753. PMID: 30829945

Prognosis

Zibold J, von Livonius B, Kolarova H, Rudolph G, Priglinger CS, Klopstock T, Catarino CB
Orphanet J Rare Dis 2022 Aug 9;17(1):310. doi: 10.1186/s13023-022-02453-z. PMID: 35945620Free PMC Article
DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Döhner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hájek R, Porkka K, Illés Á, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW
N Engl J Med 2020 Aug 13;383(7):617-629. doi: 10.1056/NEJMoa2012971. PMID: 32786187
Cui S, Yang L, Jiang H, Peng J, Shang J, Wang J, Zhang X
J Neuroophthalmol 2020 Mar;40(1):30-36. doi: 10.1097/WNO.0000000000000799. PMID: 32045392
Ebersberger U, Makowski MR, Schoepf UJ, Platz U, Schmidtler F, Rose J, Kessel A, Roth P, Antoni D, Schnackenburg B, Helmberger T, Rieber J, Hoffmann E, Leber AW
Eur Heart J Cardiovasc Imaging 2013 Dec;14(12):1174-80. Epub 2013 Aug 1 doi: 10.1093/ehjci/jet074. PMID: 23907345
Pro B, Leber B, Smith M, Fayad L, Romaguera J, Hagemeister F, Rodriguez A, McLaughlin P, Samaniego F, Zwiebel J, Lopez A, Kwak L, Younes A
Br J Haematol 2008 Nov;143(3):355-60. Epub 2008 Sep 1 doi: 10.1111/j.1365-2141.2008.07353.x. PMID: 18764869

Clinical prediction guides

Tubau-Juni N, Bassaganya-Riera J, Leber AJ, Alva SS, Hontecillas R
Inflamm Bowel Dis 2024 Jan 5;30(1):103-113. doi: 10.1093/ibd/izad124. PMID: 37436905
Zibold J, von Livonius B, Kolarova H, Rudolph G, Priglinger CS, Klopstock T, Catarino CB
Orphanet J Rare Dis 2022 Aug 9;17(1):310. doi: 10.1186/s13023-022-02453-z. PMID: 35945620Free PMC Article
Hernandez-Da-Mota S, Escalante-Razo F
Eur J Ophthalmol 2009 Mar-Apr;19(2):307-9. doi: 10.1177/112067210901900225. PMID: 19253255
La Morgia C, Achilli A, Iommarini L, Barboni P, Pala M, Olivieri A, Zanna C, Vidoni S, Tonon C, Lodi R, Vetrugno R, Mostacci B, Liguori R, Carroccia R, Montagna P, Rugolo M, Torroni A, Carelli V
Neurology 2008 Mar 4;70(10):762-70. Epub 2008 Jan 23 doi: 10.1212/01.wnl.0000295505.74234.d0. PMID: 18216301
Brown MD, Shoffner JM, Kim YL, Jun AS, Graham BH, Cabell MF, Gurley DS, Wallace DC
Am J Med Genet 1996 Jan 22;61(3):283-9. doi: 10.1002/(SICI)1096-8628(19960122)61:3<283::AID-AJMG15>3.0.CO;2-P. PMID: 8741876

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