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Diffuse leukoencephalopathy

MedGen UID:
358229
Concept ID:
C1868514
Finding
Synonym: Leukoencephalopathy, diffuse
 
HPO: HP:0006994

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDiffuse leukoencephalopathy

Conditions with this feature

Mitochondrial DNA depletion syndrome 6 (hepatocerebral type)
MedGen UID:
338045
Concept ID:
C1850406
Disease or Syndrome
MPV17-related mitochondrial DNA (mtDNA) maintenance defect presents in the vast majority of affected individuals as an early-onset encephalohepatopathic (hepatocerebral) disease that is typically associated with mtDNA depletion, particularly in the liver. A later-onset neuromyopathic disease characterized by myopathy and neuropathy, and associated with multiple mtDNA deletions in muscle, has also rarely been described. MPV17-related mtDNA maintenance defect, encephalohepatopathic form is characterized by: Hepatic manifestations (liver dysfunction that typically progresses to liver failure, cholestasis, hepatomegaly, and steatosis); Neurologic involvement (developmental delay, hypotonia, microcephaly, and motor and sensory peripheral neuropathy); Gastrointestinal manifestations (gastrointestinal dysmotility, feeding difficulties, and failure to thrive); and Metabolic derangements (lactic acidosis and hypoglycemia). Less frequent manifestations include renal tubulopathy, nephrocalcinosis, and hypoparathyroidism. Progressive liver disease often leads to death in infancy or early childhood. Hepatocellular carcinoma has been reported.
Adult-onset autosomal dominant demyelinating leukodystrophy
MedGen UID:
356995
Concept ID:
C1868512
Disease or Syndrome
LMNB1-related autosomal dominant leukodystrophy (ADLD) is a slowly progressive disorder of central nervous system white matter characterized by onset of autonomic dysfunction in the fourth to fifth decade, followed by pyramidal and cerebellar abnormalities resulting in spasticity, ataxia, and tremor. Autonomic dysfunction can include bladder dysfunction, constipation, postural hypotension, erectile dysfunction, and (less often) impaired sweating. Pyramidal signs are often more prominent in the lower extremities (e.g., spastic weakness, hypertonia, clonus, brisk deep tendon reflexes, and bilateral Babinski signs). Cerebellar signs typically appear at the same time as the pyramidal signs and include gait ataxia, dysdiadochokinesia, intention tremor, dysmetria, and nystagmus. Many individuals have sensory deficits starting in the lower limbs. Pseudobulbar palsy with dysarthria, dysphagia, and forced crying and laughing may appear in the seventh or eighth decade. Although cognitive function is usually preserved or only mildly impaired early in the disease course, dementia and psychiatric manifestations can occur as late manifestations. Affected individuals may survive for decades after onset.
Aicardi-Goutieres syndrome 9
MedGen UID:
1794176
Concept ID:
C5561966
Disease or Syndrome
Aicardi-Goutieres syndrome-9 (AGS9) is a type I interferonopathy characterized by severe developmental delay and progressive neurologic deterioration. Patients present in infancy with irritability and spasticity. Brain imaging shows diffusely abnormal white matter, cerebral atrophy, and intracranial calcification. Premature death has been associated with renal and/or hepatic failure (Uggenti et al., 2020). For a general phenotypic description and discussion of genetic heterogeneity of Aicardi-Goutieres syndrome, see AGS1 (225750).
Mitochondrial DNA depletion syndrome 20 (mngie type)
MedGen UID:
1804209
Concept ID:
C5676934
Disease or Syndrome
Mitochondrial DNA depletion syndrome-20 (MTDPS20) is an autosomal recessive multisystem disorder with variable manifestations and severity. Most patients develop symptoms in childhood, although the onset can range from infancy to the teenage years. Prominent features include severe gastrointestinal dysmotility often requiring parenteral nutrition, neurogenic bladder, and muscle weakness and atrophy. Neurologic involvement manifests as headaches, stroke-like episodes, seizures, pyramidal signs, and learning difficulties or cognitive decline. Brain imaging usually shows diffuse leukoencephalopathy and may show cerebellar atrophy. The disorder results from a defect in the maintenance and repair of mitochondrial DNA, resulting in mtDNA depletion and impaired mitochondrial function (summary by Bonora et al., 2021). For a discussion of genetic heterogeneity of mtDNA depletion syndromes, see MTDPS1 (603041).

Professional guidelines

PubMed

Ippolito A, Urban H, Ghoroghi K, Rosbach N, Lingwal N, Adam EH, Friedrichson B, Steinbicker AU, Hattingen E, Wenger KJ
Sci Rep 2022 Oct 19;12(1):17423. doi: 10.1038/s41598-022-21475-y. PMID: 36261436Free PMC Article
Konno T, Yoshida K, Mizuta I, Mizuno T, Kawarai T, Tada M, Nozaki H, Ikeda SI, Onodera O, Wszolek ZK, Ikeuchi T
Eur J Neurol 2018 Jan;25(1):142-147. Epub 2017 Oct 19 doi: 10.1111/ene.13464. PMID: 28921817Free PMC Article
Chaussenot A, Bannwarth S, Rouzier C, Vialettes B, Mkadem SA, Chabrol B, Cano A, Labauge P, Paquis-Flucklinger V
Ann Neurol 2011 Mar;69(3):501-8. Epub 2010 Dec 28 doi: 10.1002/ana.22160. PMID: 21446023

Recent clinical studies

Etiology

Radmanesh A, Derman A, Lui YW, Raz E, Loh JP, Hagiwara M, Borja MJ, Zan E, Fatterpekar GM
Radiology 2020 Oct;297(1):E223-E227. Epub 2020 May 21 doi: 10.1148/radiol.2020202040. PMID: 32437314Free PMC Article
Williams T, Houlden H, Murphy E, John N, Fox NC, Schott JM, Adams M, Davagananam I, Chataway J, Lynch DS
Pract Neurol 2020 Aug;20(4):280-286. Epub 2020 May 20 doi: 10.1136/practneurol-2020-002530. PMID: 32434903
Saitoh BY, Yamasaki R, Hiwatashi A, Matsushita T, Hayashi S, Mitsunaga Y, Maeda Y, Isobe N, Yoshida K, Ikeda SI, Kira JI
Mult Scler Relat Disord 2019 Jun;31:22-31. Epub 2019 Mar 12 doi: 10.1016/j.msard.2019.03.008. PMID: 30901701
Köhler W, Curiel J, Vanderver A
Nat Rev Neurol 2018 Feb;14(2):94-105. Epub 2018 Jan 5 doi: 10.1038/nrneurol.2017.175. PMID: 29302065
Budka H
Acta Neuropathol 1989;77(3):225-36. doi: 10.1007/BF00687573. PMID: 2538039

Diagnosis

Williams T, Houlden H, Murphy E, John N, Fox NC, Schott JM, Adams M, Davagananam I, Chataway J, Lynch DS
Pract Neurol 2020 Aug;20(4):280-286. Epub 2020 May 20 doi: 10.1136/practneurol-2020-002530. PMID: 32434903
Shi T, Li J, Tan C, Chen J
Medicine (Baltimore) 2019 May;98(22):e15802. doi: 10.1097/MD.0000000000015802. PMID: 31145310Free PMC Article
Köhler W, Curiel J, Vanderver A
Nat Rev Neurol 2018 Feb;14(2):94-105. Epub 2018 Jan 5 doi: 10.1038/nrneurol.2017.175. PMID: 29302065
Nzwalo H, Sá F, Cordeiro I, Ferreira F, Basílio C
BMJ Case Rep 2011 Sep 19;2011 doi: 10.1136/bcr.06.2011.4344. PMID: 22679254Free PMC Article
Fujioka S, Wszolek ZK
J Mol Neurosci 2011 Nov;45(3):359-65. Epub 2011 Jun 8 doi: 10.1007/s12031-011-9568-5. PMID: 21656039Free PMC Article

Therapy

Caputi L, Erbetta A, Marucci G, Pareyson D, Eoli M, Servida M, Parati E, Salsano E
J Clin Neurosci 2019 Jun;64:42-44. Epub 2019 Mar 22 doi: 10.1016/j.jocn.2019.03.021. PMID: 30910547
Mehanna R, Jimenez-Shahed J, Itin I
Am J Case Rep 2016 Dec 2;17:916-920. doi: 10.12659/ajcr.900537. PMID: 27909286Free PMC Article
Hasegawa C, Inagaki A, Yamada G, Morita K, Kitamura I, Ariyoshi K
Intern Med 2016;55(22):3393-3398. Epub 2016 Nov 15 doi: 10.2169/internalmedicine.55.7069. PMID: 27853090Free PMC Article
Ge W, Kuang H, Wei B, Bo L, Xu Z, Xu X, Geng D, Sun M
PLoS One 2014;9(8):e104533. Epub 2014 Aug 6 doi: 10.1371/journal.pone.0104533. PMID: 25098330Free PMC Article
Sundal C, Fujioka S, Van Gerpen JA, Wider C, Nicholson AM, Baker M, Shuster EA, Aasly J, Spina S, Ghetti B, Roeber S, Garbern J, Tselis A, Swerdlow RH, Miller BB, Borjesson-Hanson A, Uitti RJ, Ross OA, Stoessl AJ, Rademakers R, Josephs KA, Dickson DW, Broderick D, Wszolek ZK
Parkinsonism Relat Disord 2013 Oct;19(10):869-77. Epub 2013 Jun 17 doi: 10.1016/j.parkreldis.2013.05.013. PMID: 23787135Free PMC Article

Prognosis

Köhler W, Curiel J, Vanderver A
Nat Rev Neurol 2018 Feb;14(2):94-105. Epub 2018 Jan 5 doi: 10.1038/nrneurol.2017.175. PMID: 29302065
Kawakami I, Iseki E, Kasanuki K, Minegishi M, Sato K, Hino H, Shibuya K, Fujisawa K, Higashi S, Akiyama H, Furuta A, Takanashi M, Li Y, Hattori N, Mitsuyama Y, Arai H
J Neurol Sci 2016 Aug 15;367:349-55. Epub 2016 Jun 7 doi: 10.1016/j.jns.2016.06.013. PMID: 27423618
Sundal C, Fujioka S, Van Gerpen JA, Wider C, Nicholson AM, Baker M, Shuster EA, Aasly J, Spina S, Ghetti B, Roeber S, Garbern J, Tselis A, Swerdlow RH, Miller BB, Borjesson-Hanson A, Uitti RJ, Ross OA, Stoessl AJ, Rademakers R, Josephs KA, Dickson DW, Broderick D, Wszolek ZK
Parkinsonism Relat Disord 2013 Oct;19(10):869-77. Epub 2013 Jun 17 doi: 10.1016/j.parkreldis.2013.05.013. PMID: 23787135Free PMC Article
Fujioka S, Wszolek ZK
J Mol Neurosci 2011 Nov;45(3):359-65. Epub 2011 Jun 8 doi: 10.1007/s12031-011-9568-5. PMID: 21656039Free PMC Article
Chaussenot A, Bannwarth S, Rouzier C, Vialettes B, Mkadem SA, Chabrol B, Cano A, Labauge P, Paquis-Flucklinger V
Ann Neurol 2011 Mar;69(3):501-8. Epub 2010 Dec 28 doi: 10.1002/ana.22160. PMID: 21446023

Clinical prediction guides

Garg RK, Paliwal VK, Malhotra HS, Sharma PK
Neurol India 2021 Mar-Apr;69(2):260-271. doi: 10.4103/0028-3886.314531. PMID: 33904434
Oyanagi K, Kinoshita M, Suzuki-Kouyama E, Inoue T, Nakahara A, Tokiwai M, Arai N, Satoh JI, Aoki N, Jinnai K, Yazawa I, Arai K, Ishihara K, Kawamura M, Ishizawa K, Hasegawa K, Yagisita S, Amano N, Yoshida K, Terada S, Yoshida M, Akiyama H, Mitsuyama Y, Ikeda SI
Brain Pathol 2017 Nov;27(6):748-769. Epub 2017 Mar 2 doi: 10.1111/bpa.12443. PMID: 27608278Free PMC Article
Murakami T, Yoshida K, Segawa M, Yoshihara A, Hoshi A, Nakamura K, Ichikawa M, Suzuki O, Yokoyama Y, Toyoshima Y, Sugiura Y, Ito H, Saito K, Hashimoto Y, Kakita A, Takahashi H, Ugawa Y
BMC Neurol 2016 Aug 8;16:128. doi: 10.1186/s12883-016-0655-7. PMID: 27502482Free PMC Article
Sundal C, Van Gerpen JA, Nicholson AM, Wider C, Shuster EA, Aasly J, Spina S, Ghetti B, Roeber S, Garbern J, Borjesson-Hanson A, Tselis A, Swerdlow RH, Miller BB, Fujioka S, Heckman MG, Uitti RJ, Josephs KA, Baker M, Andersen O, Rademakers R, Dickson DW, Broderick D, Wszolek ZK
Neurology 2012 Aug 7;79(6):566-74. Epub 2012 Jul 25 doi: 10.1212/WNL.0b013e318263575a. PMID: 22843259Free PMC Article
Chaussenot A, Bannwarth S, Rouzier C, Vialettes B, Mkadem SA, Chabrol B, Cano A, Labauge P, Paquis-Flucklinger V
Ann Neurol 2011 Mar;69(3):501-8. Epub 2010 Dec 28 doi: 10.1002/ana.22160. PMID: 21446023

Recent systematic reviews

Mickeviciute GC, Valiuskyte M, Plattén M, Wszolek ZK, Andersen O, Danylaité Karrenbauer V, Ineichen BV, Granberg T
J Intern Med 2022 Mar;291(3):269-282. Epub 2021 Dec 22 doi: 10.1111/joim.13420. PMID: 34875121
Adams SJ, Kirk A, Auer RN
J Clin Neurosci 2018 Feb;48:42-49. Epub 2017 Nov 6 doi: 10.1016/j.jocn.2017.10.060. PMID: 29122458

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