Format

Send to:

Choose Destination

Links from PubMed

Hereditary diffuse leukoencephalopathy with spheroids(HDLS)

MedGen UID:
341741
Concept ID:
C1857300
Disease or Syndrome
Synonyms: CSF1R-Related Hereditary Diffuse Leukoencephalopathy with Spheroids; DEMENTIA, FAMILIAL, NEUMANN TYPE; Gliosis, familial progressive subcortical; HDLS; LEUKOENCEPHALOPATHY WITH NEUROAXONAL SPHEROIDS, AUTOSOMAL DOMINANT; LEUKOENCEPHALOPATHY, ADULT-ONSET, WITH AXONAL SPHEROIDS AND PIGMENTED GLIA; SUBCORTICAL GLIOSIS OF NEUMANN
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
 
Gene (location): CSF1R (5q32)
OMIM®: 221820

Disease characteristics

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), which includes both hereditary diffuse leukoencephalopathy with spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD), is characterized by executive dysfunction, memory decline, personality changes, motor impairments, and seizures. A frontal lobe syndrome (e.g., loss of judgment, lack of social inhibitors, lack of insight, and motor persistence) usually appears early in the disease course. The mean age of onset is usually in the fourth decade. Affected individuals eventually become bedridden with spasticity and rigidity. The disease course ranges from two to 30 or more years (mean: 8 years). [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  GeneReview Scope  |  Diagnosis  |  Clinical Characteristics  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Christina Sundal  |  Zbigniew Wszolek   view full author information

Additional descriptions

From OMIM
Hereditary diffuse leukoencephalopathy with spheroids is an autosomal dominant adult-onset rapidly progressive neurodegenerative disorder characterized by variable behavioral, cognitive, and motor changes. Patients often die of dementia within 6 years of onset. Brain imaging shows patchy abnormalities in the cerebral white matter, predominantly affecting the frontal and parietal lobes (summary by Rademakers et al., 2012).  http://www.omim.org/entry/221820
From GHR
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a neurological condition characterized by changes to certain areas of the brain. A hallmark of ALSP is leukoencephalopathy, which is the alteration of a type of brain tissue called white matter. White matter consists of nerve fibers (axons) covered by a substance called myelin that insulates and protects them. The axons extend from nerve cells (neurons) and transmit nerve impulses throughout the body. Areas of damage to this brain tissue (white matter lesions) can be seen with magnetic resonance imaging (MRI). Another feature of ALSP is swellings called spheroids in the axons of the brain, which are a sign of axon damage. Also common in ALSP are abnormally pigmented glial cells. Glial cells are specialized brain cells that protect and maintain neurons. Damage to myelin and neurons is thought to contribute to many of the neurological signs and symptoms in people with ALSP.Symptoms of ALSP usually begin in a person's forties and worsen over time. Personality changes, including depression and a loss of social inhibitions, are among the earliest symptoms of ALSP. Affected individuals may develop memory loss and loss of executive function, which is the ability to plan and implement actions and develop problem-solving strategies. Loss of this function impairs skills such as impulse control, self-monitoring, and focusing attention appropriately. Some people with ALSP have mild seizures, usually only when the condition begins. As ALSP progresses, it causes a severe decline in thinking and reasoning abilities (dementia).Over time, motor skills are affected, and people with ALSP may have difficulty walking. Many develop a pattern of movement abnormalities known as parkinsonism, which includes unusually slow movement (bradykinesia), involuntary trembling (tremor), and muscle stiffness (rigidity). The pattern of cognitive and motor problems are variable, even among individuals in the same family, although almost all affected individuals ultimately become unable to walk, speak, and care for themselves.ALSP was previously thought to be two separate conditions, hereditary diffuse leukoencephalopathy with spheroids (HDLS) and familial pigmentary orthochromatic leukodystrophy (POLD), both of which cause very similar white matter damage and cognitive and movement problems. POLD was thought to be distinguished by the presence of pigmented glial cells and an absence of spheroids; however, people with HDLS can have pigmented cells, too, and people with POLD can have spheroids. HDLS and POLD are now considered to be part of the same disease spectrum, which researchers have recommended calling ALSP.  https://ghr.nlm.nih.gov/condition/adult-onset-leukoencephalopathy-with-axonal-spheroids-and-pigmented-glia

Clinical features

Gliosis
MedGen UID:
4899
Concept ID:
C0017639
Pathologic Function
Gliosis is the focal proliferation of glial cells in the central nervous system.
Leukoencephalopathy
MedGen UID:
78722
Concept ID:
C0270612
Disease or Syndrome
Any of various diseases affecting the white matter of the central nervous system.
Abnormality of the cerebral white matter
MedGen UID:
181756
Concept ID:
C0948163
Pathologic Function
Non-specific white matter changes in the BRAIN, often seen after age 65. Changes include loss of AXONS; MYELIN pallor, GLIOSIS, loss of ependymal cells, and enlarged perivascular spaces. Leukoaraiosis is a risk factor for DEMENTIA and CEREBROVASCULAR DISORDERS.
Neuronal loss in central nervous system
MedGen UID:
342515
Concept ID:
C1850496
Finding

Recent clinical studies

Etiology

Granberg T, Hashim F, Andersen O, Sundal C, Karrenbauer VD
Eur J Neurol 2016 Apr;23(4):817-22. Epub 2016 Jan 12 doi: 10.1111/ene.12948. PMID: 26756564
Kinoshita M, Kondo Y, Yoshida K, Fukushima K, Hoshi K, Ishizawa K, Araki N, Yazawa I, Washimi Y, Saitoh B, Kira J, Ikeda S
Intern Med 2014;53(1):21-7. PMID: 24390523
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

Robinson JL, Suh E, Wood EM, Lee EB, Coslett HB, Raible K, Lee VM, Trojanowski JQ, Van Deerlin VM
Acta Neuropathol Commun 2015 Jul 4;3:42. doi: 10.1186/s40478-015-0219-x. PMID: 26141825Free 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):328-33. Epub 2014 Oct 13 doi: 10.1111/ene.12572. PMID: 25311247Free PMC Article
Kitani-Morii F, Kasai T, Tomonaga K, Saito K, Mizuta I, Yoshioka A, Nakagawa M, Mizuno T
Intern Med 2014;53(12):1377-80. Epub 2014 Jun 15 PMID: 24930661
Terasawa Y, Osaki Y, Kawarai T, Sugimoto T, Orlacchio A, Abe T, Izumi Y, Kaji R
J Neurol Sci 2013 Dec 15;335(1-2):213-5. Epub 2013 Aug 30 doi: 10.1016/j.jns.2013.08.027. PMID: 24094860
Kondo Y, Kinoshita M, Fukushima K, Yoshida K, Ikeda S
Intern Med 2013;52(4):503-6. Epub 2013 Feb 15 PMID: 23411710

Therapy

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

Shu Y, Long L, Liao S, Yang J, Li J, Qiu W, Yang Y, Bao J, Wu A, Hu X, Lu Z
BMC Neurol 2016 Sep 13;16:171. doi: 10.1186/s12883-016-0694-0. PMID: 27619214Free PMC Article
Meyer-Ohlendorf M, Braczynski A, Al-Qaisi O, Gessler F, Biskup S, Weise L, Steinbach JP, Wagner M, Mittelbronn M, Bähr O
BMC Neurol 2015 Jul 4;15:103. doi: 10.1186/s12883-015-0368-3. PMID: 26141177Free 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):328-33. Epub 2014 Oct 13 doi: 10.1111/ene.12572. PMID: 25311247Free 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
Van Gerpen JA, Wider C, Broderick DF, Dickson DW, Brown LA, Wszolek ZK
Neurology 2008 Sep 16;71(12):925-9. doi: 10.1212/01.wnl.0000325916.30701.21. PMID: 18794495Free PMC Article

Clinical prediction guides

Granberg T, Hashim F, Andersen O, Sundal C, Karrenbauer VD
Eur J Neurol 2016 Apr;23(4):817-22. Epub 2016 Jan 12 doi: 10.1111/ene.12948. PMID: 26756564
Riku Y, Ando T, Goto Y, Mano K, Iwasaki Y, Sobue G, Yoshida M
J Neuropathol Exp Neurol 2014 Dec;73(12):1183-90. doi: 10.1097/NEN.0000000000000139. PMID: 25383640
Bender B, Klose U, Lindig T, Biskup S, Nägele T, Schöls L, Karle KN
J Neurol 2014 Dec;261(12):2351-9. Epub 2014 Sep 20 doi: 10.1007/s00415-014-7509-2. PMID: 25239393
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
Terasawa Y, Osaki Y, Kawarai T, Sugimoto T, Orlacchio A, Abe T, Izumi Y, Kaji R
J Neurol Sci 2013 Dec 15;335(1-2):213-5. Epub 2013 Aug 30 doi: 10.1016/j.jns.2013.08.027. PMID: 24094860

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center