U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2(PLOSL2)

MedGen UID:
1648374
Concept ID:
C4748657
Disease or Syndrome
Synonyms: PLOSL2; POLYCYSTIC LIPOMEMBRANOUS OSTEODYSPLASIA WITH SCLEROSING LEUKOENCEPHALOPATHY 2
 
Gene (location): TREM2 (6p21.1)
 
Monarch Initiative: MONDO:0020750
OMIM®: 618193

Definition

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy-2 (PLOSL2), or Nasu-Hakola disease, is a recessively inherited presenile frontal dementia with leukoencephalopathy and basal ganglia calcification. In most cases the disorder first manifests in early adulthood as pain and swelling in ankles and feet, followed by bone fractures. Neurologic symptoms manifest in the fourth decade of life as a frontal lobe syndrome with loss of judgment, euphoria, and disinhibition. Progressive decline in other cognitive domains begins to develop at about the same time. The disorder culminates in a profound dementia and death by age 50 years (summary by Klunemann et al., 2005). For a discussion of genetic heterogeneity of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, see 221770. [from OMIM]

Clinical features

From HPO
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Agnosia
MedGen UID:
174
Concept ID:
C0001816
Mental or Behavioral Dysfunction
Alteration or impairment in the processing or interpretation of sensory information can lead to abnormal perceptions or experiences.
Aphasia
MedGen UID:
8159
Concept ID:
C0003537
Mental or Behavioral Dysfunction
An acquired language impairment of some or all of the abilities to produce or comprehend speech and to read or write.
Apraxia
MedGen UID:
8166
Concept ID:
C0003635
Mental or Behavioral Dysfunction
A defect in the understanding of complex motor commands and in the execution of certain learned movements, i.e., deficits in the cognitive components of learned movements.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
EEG abnormality
MedGen UID:
56235
Concept ID:
C0151611
Finding
Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp.
Memory impairment
MedGen UID:
68579
Concept ID:
C0233794
Mental or Behavioral Dysfunction
An impairment of memory as manifested by a reduced ability to remember things such as dates and names, and increased forgetfulness.
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.
CNS demyelination
MedGen UID:
137898
Concept ID:
C0338474
Disease or Syndrome
A loss of myelin from nerve fibers in the central nervous system.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Disinhibition
MedGen UID:
633911
Concept ID:
C0474398
Finding
Reduced ability to control, or a failure to resist a temptation, urge, or impulse. Examples include disregard for social conventions, general impulsivity, and poor risk assessment.
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. In general, this can refer to neurological diseases but also fractures or other sources of pain that is triggered upon walking. However, in the current context gait disturbance refers to difficulty walking on the basis of a neurological or muscular disease.
Primitive reflex
MedGen UID:
333065
Concept ID:
C1838319
Finding
The primitive reflexes are a group of behavioral motor responses which are found in normal early development, are subsequently inhibited, but may be released from inhibition by cerebral, usually frontal, damage. They are thus part of a broader group of reflexes which reflect release phenomena, such as exaggerated stretch reflexes and extensor plantars. They do however involve more complex motor responses than such simple stretch reflexes, and are often a normal feature in the neonate or infant.
Caudate atrophy
MedGen UID:
346745
Concept ID:
C1858116
Disease or Syndrome
T2 hypointense thalamus
MedGen UID:
868382
Concept ID:
C4022776
Finding
A darker than expected T2 signal on magnetic resonance imaging (MRI) of the thalamus. This term refers to a diffuse hypointensity affecting the entire thalamus.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Bone cyst
MedGen UID:
2696
Concept ID:
C0005937
Anatomical Abnormality
A fluid filled cavity that develops with a bone.
Pathologic fracture
MedGen UID:
42095
Concept ID:
C0016663
Pathologic Function
A pathologic fracture occurs when a bone breaks in an area that is weakened secondarily to another disease process such as tumor, infection, and certain inherited bone disorders. A pathologic fracture can occur without a degree of trauma required to cause fracture in healthy bone.
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
Basal ganglia calcification
MedGen UID:
234651
Concept ID:
C1389280
Pathologic Function
The presence of calcium deposition affecting one or more structures of the basal ganglia.

Recent clinical studies

Etiology

Berdyński M, Ludwiczak J, Barczak A, Barcikowska-Kotowicz M, Kuźma-Kozakiewicz M, Dunin-Horkawicz S, Żekanowski C, Borzemska B
J Alzheimers Dis 2022;89(4):1211-1219. doi: 10.3233/JAD-220210. PMID: 36031890
Zhou SL, Tan CC, Hou XH, Cao XP, Tan L, Yu JT
J Alzheimers Dis 2019;68(3):1171-1184. doi: 10.3233/JAD-181038. PMID: 30883352
Carmona S, Zahs K, Wu E, Dakin K, Bras J, Guerreiro R
Lancet Neurol 2018 Aug;17(8):721-730. Epub 2018 Jul 17 doi: 10.1016/S1474-4422(18)30232-1. PMID: 30033062
Walter J
J Biol Chem 2016 Feb 26;291(9):4334-41. Epub 2015 Dec 22 doi: 10.1074/jbc.R115.704981. PMID: 26694609Free PMC Article
Pelham CJ, Pandya AN, Agrawal DK
Expert Opin Ther Pat 2014 Dec;24(12):1383-95. Epub 2014 Nov 1 doi: 10.1517/13543776.2014.977865. PMID: 25363248Free PMC Article

Diagnosis

Rashid Nezhad A, Olfati N, Shoeibi A, Rezaei Talab F, Soltani Sabi M
Alzheimer Dis Assoc Disord 2023 Apr-Jun 01;37(2):168-170. Epub 2023 Feb 20 doi: 10.1097/WAD.0000000000000547. PMID: 36820836
Kaivola K, Jansson L, Saarentaus E, Kiviharju A, Rantalainen V, Eriksson JG, Strandberg TE, Polvikoski T, Myllykangas L, Tienari PJ
Neurobiol Aging 2018 Apr;64:159.e1-159.e4. Epub 2017 Dec 18 doi: 10.1016/j.neurobiolaging.2017.12.008. PMID: 29336840
Solje E, Hartikainen P, Valori M, Vanninen R, Tiihonen J, Hakola P, Tienari PJ, Remes AM
Neurobiol Aging 2014 Jul;35(7):1780.e13-7. Epub 2014 Feb 5 doi: 10.1016/j.neurobiolaging.2014.01.149. PMID: 24612676
Guerreiro R, Bilgic B, Guven G, Brás J, Rohrer J, Lohmann E, Hanagasi H, Gurvit H, Emre M
Neurobiol Aging 2013 Dec;34(12):2890.e1-5. Epub 2013 Jul 17 doi: 10.1016/j.neurobiolaging.2013.06.005. PMID: 23870839Free PMC Article
Kaneko M, Sano K, Nakayama J, Amano N
Neuropathology 2010 Oct;30(5):463-70. doi: 10.1111/j.1440-1789.2010.01127.x. PMID: 20500450

Therapy

Swain PS, Panda S, Pati S, Dehury B
J Mol Model 2023 Nov 4;29(11):360. doi: 10.1007/s00894-023-05770-7. PMID: 37924367
Pekkarinen P, Hovatta I, Hakola P, Järvi O, Kestilä M, Lenkkeri U, Adolfsson R, Holmgren G, Nylander PO, Tranebjaerg L, Terwilliger JD, Lönnqvist J, Peltonen L
Am J Hum Genet 1998 Feb;62(2):362-72. doi: 10.1086/301722. PMID: 9463329Free PMC Article

Prognosis

Dash R, Choi HJ, Moon IS
Sci Rep 2020 Feb 27;10(1):3663. doi: 10.1038/s41598-020-60561-x. PMID: 32107424Free PMC Article
Darwent L, Carmona S, Lohmann E, Guven G, Kun-Rodrigues C, Bilgic B, Hanagasi H, Gurvit H, Erginel-Unaltuna N, Pak M, Hardy J, Singleton A, Brás J, Guerreiro R
Neurobiol Aging 2017 Oct;58:240.e1-240.e3. Epub 2017 Jun 28 doi: 10.1016/j.neurobiolaging.2017.06.019. PMID: 28716534Free PMC Article
Solje E, Hartikainen P, Valori M, Vanninen R, Tiihonen J, Hakola P, Tienari PJ, Remes AM
Neurobiol Aging 2014 Jul;35(7):1780.e13-7. Epub 2014 Feb 5 doi: 10.1016/j.neurobiolaging.2014.01.149. PMID: 24612676
Chouery E, Delague V, Bergougnoux A, Koussa S, Serre JL, Mégarbané A
Hum Mutat 2008 Sep;29(9):E194-204. doi: 10.1002/humu.20836. PMID: 18546367

Clinical prediction guides

Dash R, Choi HJ, Moon IS
Sci Rep 2020 Feb 27;10(1):3663. doi: 10.1038/s41598-020-60561-x. PMID: 32107424Free PMC Article
Kaivola K, Jansson L, Saarentaus E, Kiviharju A, Rantalainen V, Eriksson JG, Strandberg TE, Polvikoski T, Myllykangas L, Tienari PJ
Neurobiol Aging 2018 Apr;64:159.e1-159.e4. Epub 2017 Dec 18 doi: 10.1016/j.neurobiolaging.2017.12.008. PMID: 29336840
Darwent L, Carmona S, Lohmann E, Guven G, Kun-Rodrigues C, Bilgic B, Hanagasi H, Gurvit H, Erginel-Unaltuna N, Pak M, Hardy J, Singleton A, Brás J, Guerreiro R
Neurobiol Aging 2017 Oct;58:240.e1-240.e3. Epub 2017 Jun 28 doi: 10.1016/j.neurobiolaging.2017.06.019. PMID: 28716534Free PMC Article
Mori Y, Yoshino Y, Ochi S, Yamazaki K, Kawabe K, Abe M, Kitano T, Ozaki Y, Yoshida T, Numata S, Mori T, Iga J, Kuroda N, Ohmori T, Ueno S
PLoS One 2015;10(9):e0136835. Epub 2015 Sep 2 doi: 10.1371/journal.pone.0136835. PMID: 26332043Free PMC Article
Satoh J, Tabunoki H, Ishida T, Yagishita S, Jinnai K, Futamura N, Kobayashi M, Toyoshima I, Yoshioka T, Enomoto K, Arai N, Arima K
Neuropathology 2011 Aug;31(4):363-75. Epub 2010 Dec 1 doi: 10.1111/j.1440-1789.2010.01174.x. PMID: 21118401

Recent systematic reviews

Zhou SL, Tan CC, Hou XH, Cao XP, Tan L, Yu JT
J Alzheimers Dis 2019;68(3):1171-1184. doi: 10.3233/JAD-181038. PMID: 30883352

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...