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Leukoencephalopathy, hereditary diffuse, with spheroids 2(HDLS2)

MedGen UID:
1794254
Concept ID:
C5562044
Disease or Syndrome
Synonyms: HDLS2; LEUKOENCEPHALOPATHY, HEREDITARY DIFFUSE, WITH SPHEROIDS, SWEDISH TYPE
 
Gene (location): AARS1 (16q22.1)
 
Monarch Initiative: MONDO:0030634
OMIM®: 619661

Definition

Hereditary diffuse leukoencephalopathy with spheroids-2 (HDLS2) is an autosomal dominant neurodegenerative disorder characterized by progressive cognitive and executive dysfunction, psychiatric disturbances, and neurologic symptoms, such as gait abnormalities, paresis, seizures, and rigidity. Symptom onset is usually in adulthood, although earlier onset has been reported. Some patients have an acute encephalopathic course with severe neurologic decline resulting in early death, whereas other patients have a more protracted and chronic disease course. Neuropathologic examination shows a leukoencephalopathy with axonal spheroids and myelination defects (summary by Sundal et al., 2012). For a discussion of genetic heterogeneity of HDLS, see HDLS1 (221820). [from OMIM]

Clinical features

From HPO
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.
Grasp reflex
MedGen UID:
115944
Concept ID:
C0234175
Organism Function
A type of primitive reflex that can be elicated when the hand of the examiner is gently inserted into the palm of the patient's hand. The palmar surface is stroked or simply touched. The flexor surfaces of the fingers may be stimulated also by the examiner's fingers. The stimulus should be in a distal direction. With a positive response, the patient grasps the examiner's hand with variable strength and continues to grasp as the examiner's hand is moved. Ability to release the grip voluntarily depends on the activity of the reflex; some patients can do so readily, while others can even be lifted off the bed, since the grasp has such power [NCBI Books:NBK395].
Mental deterioration
MedGen UID:
66713
Concept ID:
C0234985
Mental or Behavioral Dysfunction
Loss of previously present mental abilities, generally in adults.
Personality changes
MedGen UID:
66817
Concept ID:
C0240735
Mental or Behavioral Dysfunction
An abnormal shift in patterns of thinking, acting, or feeling.
Sensory ataxia
MedGen UID:
66020
Concept ID:
C0240991
Sign or Symptom
Incoordination of movement caused by a deficit in the sensory nervous system. Sensory ataxia can be distinguished from cerebellar ataxia by asking the patient to close his or her eyes. Persons with cerebellar ataxia show only a minimal worsening of symptoms, whereas persons with sensory ataxia show a marked worsening of symptoms.
Leukoencephalopathy
MedGen UID:
78722
Concept ID:
C0270612
Disease or Syndrome
This term describes abnormality of the white matter of the cerebrum resulting from damage to the myelin sheaths of nerve cells.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Vegetative state
MedGen UID:
182977
Concept ID:
C0917808
Disease or Syndrome
The absence of wakefulness and consciousness, but in contrast to a coma, there is involuntary opening of the eyes and movements such as teeth grinding, yawning, or thrashing of the extremities.
Rigidity
MedGen UID:
7752
Concept ID:
C0026837
Sign or Symptom
Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.
Cheyne-Stokes respiration
MedGen UID:
3359
Concept ID:
C0008039
Sign or Symptom
An abnormal pattern of respiration characterized by cycles of respiration that are increasingly deeper then shallower with possible periods of apnea. Affected patients may display a 10 to 20 second episode of hypoventilation or apnea, followed by respiration of increased depth and frequency over the course of about one minute. The cycle repeats every 45 seconds to 3 minutes.
Hemianopia
MedGen UID:
9193
Concept ID:
C0018979
Finding
Partial or complete loss of vision in one half of the visual field of one or both eyes.

Professional guidelines

PubMed

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

Recent clinical studies

Etiology

Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
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: 29302065Free PMC Article
Konno T, Tada M, Tada M, Koyama A, Nozaki H, Harigaya Y, Nishimiya J, Matsunaga A, Yoshikura N, Ishihara K, Arakawa M, Isami A, Okazaki K, Yokoo H, Itoh K, Yoneda M, Kawamura M, Inuzuka T, Takahashi H, Nishizawa M, Onodera O, Kakita A, Ikeuchi T
Neurology 2014 Jan 14;82(2):139-48. Epub 2013 Dec 13 doi: 10.1212/WNL.0000000000000046. PMID: 24336230Free PMC Article
Karle KN, Biskup S, Schüle R, Schweitzer KJ, Krüger R, Bauer P, Bender B, Nägele T, Schöls L
Neurology 2013 Dec 3;81(23):2039-44. Epub 2013 Nov 6 doi: 10.1212/01.wnl.0000436945.01023.ac. PMID: 24198292
Graff-Radford J, Rubin MN, Jones DT, Aksamit AJ, Ahlskog JE, Knopman DS, Petersen RC, Boeve BF, Josephs KA
J Neurol 2013 Jul;260(7):1880-8. Epub 2013 Apr 10 doi: 10.1007/s00415-013-6898-y. PMID: 23572346Free PMC Article

Diagnosis

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
Tokumaru AM, Saito Y, Murayma S
Magn Reson Imaging Clin N Am 2021 May;29(2):163-183. doi: 10.1016/j.mric.2021.02.001. PMID: 33902901
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
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: 29302065Free PMC Article
Stabile C, Taglia I, Battisti C, Bianchi S, Federico A
Neurol Sci 2016 Sep;37(9):1565-9. Epub 2016 Jun 23 doi: 10.1007/s10072-016-2634-6. PMID: 27338940

Prognosis

Mangeat G, Ouellette R, Wabartha M, De Leener B, Plattén M, Danylaité Karrenbauer V, Warntjes M, Stikov N, Mainero C, Cohen-Adad J, Granberg T
J Neuroimaging 2020 Sep;30(5):674-682. Epub 2020 May 26 doi: 10.1111/jon.12725. PMID: 32453488
Makary MS, Awan U, Kisanuki YY, Slone HW
Neuroradiol J 2019 Apr;32(2):139-142. Epub 2019 Jan 7 doi: 10.1177/1971400918822136. PMID: 30614382Free 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: 29302065Free PMC Article
Sundal C, Baker M, Karrenbauer V, Gustavsen M, Bedri S, Glaser A, Myhr KM, Haugarvoll K, Zetterberg H, Harbo H, Kockum I, Hillert J, Wszolek Z, Rademakers R, Andersen O
Eur J Neurol 2015 Feb;22(2):328-333. Epub 2014 Oct 13 doi: 10.1111/ene.12572. PMID: 25311247Free 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

Clinical prediction guides

Mangeat G, Ouellette R, Wabartha M, De Leener B, Plattén M, Danylaité Karrenbauer V, Warntjes M, Stikov N, Mainero C, Cohen-Adad J, Granberg T
J Neuroimaging 2020 Sep;30(5):674-682. Epub 2020 May 26 doi: 10.1111/jon.12725. PMID: 32453488
Kempthorne L, Yoon H, Madore C, Smith S, Wszolek ZK, Rademakers R, Kim J, Butovsky O, Dickson DW
Acta Neuropathol Commun 2020 May 19;8(1):72. doi: 10.1186/s40478-020-00947-0. PMID: 32430064Free PMC Article
Kondo Y, Matsushima A, Nagasaki S, Nakamura K, Sekijima Y, Yoshida K
Eur J Neurol 2020 Feb;27(2):369-375. Epub 2019 Oct 15 doi: 10.1111/ene.14086. PMID: 31520500Free PMC Article
Konno T, Tada M, Tada M, Koyama A, Nozaki H, Harigaya Y, Nishimiya J, Matsunaga A, Yoshikura N, Ishihara K, Arakawa M, Isami A, Okazaki K, Yokoo H, Itoh K, Yoneda M, Kawamura M, Inuzuka T, Takahashi H, Nishizawa M, Onodera O, Kakita A, Ikeuchi T
Neurology 2014 Jan 14;82(2):139-48. Epub 2013 Dec 13 doi: 10.1212/WNL.0000000000000046. PMID: 24336230Free PMC Article
Sundal C, Ekholm S, Nordborg C, Jönsson L, Börjesson-Hanson A, Lindén T, Zetterberg H, Viitanen M, Andersen O
Acta Neurol Scand 2012 Jul;126(1):67-75. Epub 2011 Nov 18 doi: 10.1111/j.1600-0404.2011.01624.x. PMID: 22098561

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

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