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Neuronal ceroid lipofuscinosis 3(CLN3)

MedGen UID:
155549
Concept ID:
C0751383
Disease or Syndrome
Synonyms: CLN3; CLN3 Disease; CLN3-Related Neuronal Ceroid-Lipofuscinosis; Spielmeyer Sjogren disease
SNOMED CT: Juvenile neuronal ceroid lipofuscinosis (61663001); Batten-Mayou disease (61663001); Spielmeyer-Vogt disease (61663001); Amaurotic idiocy, juvenile type (61663001); Cerebral lipidosis, myoclonic variant (61663001); Batten-Spielmeyer-Vogt disease (61663001); Cerebral lipidosis myoclonic variant (61663001); Batten-Mayou syndrome (61663001); Amaurotic idiocy juvenile type (61663001); Spielmeyer-Vogt type neuronal ceroid lipofuscinosis (61663001)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): CLN3 (16p12.1)
 
Monarch Initiative: MONDO:0008767
OMIM®: 204200
Orphanet: ORPHA228346

Definition

The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005). The hallmark of CLN3 is the ultrastructural pattern of lipopigment with a 'fingerprint' profile, which can have 3 different appearances: pure within a lysosomal residual body; in conjunction with curvilinear or rectilinear profiles; and as a small component within large membrane-bound lysosomal vacuoles. The combination of fingerprint profiles within lysosomal vacuoles is a regular feature of blood lymphocytes from patients with CLN3 (Mole et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (256730). [from OMIM]

Additional description

From MedlinePlus Genetics
CLN3 disease is an inherited disorder that primarily affects the nervous system. After 4 to 6 years of normal development, children with this condition develop vision impairment, intellectual disability, movement problems, speech difficulties, and seizures, which worsen over time.

In children with CLN3 disease, problems with vision often begin between the ages of 4 and 8 years. Vision impairment is caused by a breakdown of the light-sensitive tissue at the back of the eye (retinal degeneration), which worsens with age. People with CLN3 disease are often blind by late childhood or adolescence. Also around age 4 to 8, children with CLN3 disease start to fall behind in school. They have difficulty learning new information and lose previously acquired skills (developmental regression), usually beginning with loss of the ability to speak in complete sentences.

Seizures and movement abnormalities often develop in adolescence in people with CLN3 disease. These abnormalities include muscle rigidity or stiffness, clumsiness, slow or diminished movements (hypokinesia), and a stooped posture. Over time, affected individuals lose the ability to walk or sit independently and require wheelchair assistance. Rarely, people with CLN3 disease develop a distorted view of reality (psychosis) or false perceptions (hallucinations). Some affected individuals have an abnormal heart rhythm (arrhythmia) later in life. Most people with CLN3 disease live into early adulthood.

CLN3 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which may also be collectively referred to as Batten disease. All these disorders affect the nervous system and typically cause worsening problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype.  https://medlineplus.gov/genetics/condition/cln3-disease

Clinical features

From HPO
Concentric hypertrophic cardiomyopathy
MedGen UID:
68651
Concept ID:
C0238044
Finding
Hypertrophic cardiomyopathy with an symmetrical and concentric pattern of hypertrophy.
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
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.
Psychotic disorder
MedGen UID:
19568
Concept ID:
C0033975
Mental or Behavioral Dysfunction
A condition characterized by changes in personality and thought patterns, often accompanied by hallucinations and delusional beliefs, is known as psychosis.
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.
Abnormality of extrapyramidal motor function
MedGen UID:
115941
Concept ID:
C0234133
Sign or Symptom
A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless).
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Parkinsonian disorder
MedGen UID:
66079
Concept ID:
C0242422
Disease or Syndrome
Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
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.
Psychomotor deterioration
MedGen UID:
373191
Concept ID:
C1836842
Finding
Loss of previously present mental and motor abilities.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
Increased extraneuronal autofluorescent lipopigment
MedGen UID:
347957
Concept ID:
C1859828
Finding
Lipofuscin, a generic term applied to autofluorescent lipopigment, is a mixture of protein and lipid that accumulates in most aging cells, particularly those involved in high lipid turnover (e.g., the adrenal medulla) or phagocytosis of other cell types (e g., the retinal pigment epithelium or RPE; macrophage). This term pertains if there is an increase in the extraneuronal accumulation of lipofuscin (also known as autofluorescent lipoprotein) more than expected for the age of the patient.
Abnormal cerebellum morphology
MedGen UID:
400925
Concept ID:
C1866129
Anatomical Abnormality
Any structural abnormality of the cerebellum.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Increased neuronal autofluorescent lipopigment
MedGen UID:
892355
Concept ID:
C4025728
Finding
Lipofuscin, a generic term applied to autofluorescent lipopigment, is a mixture of protein and lipid that accumulates in most aging cells, particularly those involved in high lipid turnover (e.g., the adrenal medulla) or phagocytosis of other cell types (e g., the retinal pigment epithelium or RPE; macrophage). This term pertains if there is an increase in the neuronal accumulation of lipofuscin (also known as autofluorescent lipoprotein) more than expected for the age of the patient.
Vacuolated lymphocytes
MedGen UID:
332307
Concept ID:
C1836855
Finding
The presence of clear, sharply defined vacuoles in the lymphocyte cytoplasm.
Glaucoma
MedGen UID:
42224
Concept ID:
C0017601
Disease or Syndrome
Glaucoma refers loss of retinal ganglion cells in a characteristic pattern of optic neuropathy usually associated with increased intraocular pressure.
Macular degeneration
MedGen UID:
7434
Concept ID:
C0024437
Disease or Syndrome
A nonspecific term denoting degeneration of the retinal pigment epithelium and/or retinal photoreceptor cells of the macula lutea.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Retinal degeneration
MedGen UID:
48432
Concept ID:
C0035304
Finding
A nonspecific term denoting degeneration of the retinal pigment epithelium and/or retinal photoreceptor cells.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
Blindness
MedGen UID:
99138
Concept ID:
C0456909
Disease or Syndrome
Blindness is the condition of lacking visual perception defined as a profound reduction in visual perception. On the 6m visual acuity scale, blindness is defined as less than 3/60. On the 20ft visual acuity scale, blindness is defined as less than 20/400. On the decimal visual acuity scale, blindness is defined as less than 0.05. Blindness is typically characterized by a visual field of no greater than 10 degrees in radius around central fixation.
Progressive visual loss
MedGen UID:
326867
Concept ID:
C1839364
Finding
A reduction of previously attained ability to see.
Undetectable electroretinogram
MedGen UID:
383742
Concept ID:
C1855685
Finding
Lack of any response to stimulation upon electroretinography.
Rod-cone dystrophy
MedGen UID:
1632921
Concept ID:
C4551714
Disease or Syndrome
An inherited retinal disease subtype in which the rod photoreceptors appear to be more severely affected than the cone photoreceptors. Typical presentation is with nyctalopia (due to rod dysfunction) followed by loss of mid-peripheral field of vision, which gradually extends and leaves many patients with a small central island of vision due to the preservation of macular cones.
Fingerprint intracellular accumulation of autofluorescent lipopigment storage material
MedGen UID:
324619
Concept ID:
C1836851
Finding
An intracellular accumulation of autofluorescent lipopigment storage material in a trabecular or fingerprint-like pattern.
Curvilinear intracellular accumulation of autofluorescent lipopigment storage material
MedGen UID:
323011
Concept ID:
C1836852
Finding
An intracellular accumulation of autofluorescent lipopigment storage material in a curved pattern.

Professional guidelines

PubMed

Sampaio LPB, Manreza MLG, Pessoa A, Gurgel-Giannetti J, Coan AC, Júnior HVL, Embiruçu EK, Henriques-Souza AMM, Kok F
Arq Neuropsiquiatr 2023 Mar;81(3):284-295. Epub 2023 Apr 14 doi: 10.1055/s-0043-1761434. PMID: 37059438Free PMC Article
Rus CM, Weissensteiner T, Pereira C, Susnea I, Danquah BD, Morales Torres G, Rocha ME, Cozma C, Saravanakumar D, Mannepalli S, Kandaswamy KK, Di Bucchianico S, Zimmermann R, Rolfs A, Bauer P, Beetz C
Orphanet J Rare Dis 2022 May 3;17(1):179. doi: 10.1186/s13023-022-02288-8. PMID: 35505348Free PMC Article
Aungaroon G, Hallinan B, Jain P, Horn PS, Spaeth C, Arya R
Pediatr Neurol 2016 Jul;60:42-48.e4. Epub 2016 Apr 8 doi: 10.1016/j.pediatrneurol.2016.03.018. PMID: 27238410

Recent clinical studies

Etiology

Dang Do AN, Baker EH, Farmer CA, Soldatos AG, Thurm AE, Porter FD
Mol Genet Metab 2023 May;139(1):107584. Epub 2023 Apr 15 doi: 10.1016/j.ymgme.2023.107584. PMID: 37086568Free PMC Article
Deneubourg C, Ramm M, Smith LJ, Baron O, Singh K, Byrne SC, Duchen MR, Gautel M, Eskelinen EL, Fanto M, Jungbluth H
Autophagy 2022 Mar;18(3):496-517. Epub 2021 Aug 19 doi: 10.1080/15548627.2021.1943177. PMID: 34130600Free PMC Article
Johnson TB, Cain JT, White KA, Ramirez-Montealegre D, Pearce DA, Weimer JM
Nat Rev Neurol 2019 Mar;15(3):161-178. doi: 10.1038/s41582-019-0138-8. PMID: 30783219Free PMC Article
Kälviäinen R
Semin Neurol 2015 Jun;35(3):293-9. Epub 2015 Jun 10 doi: 10.1055/s-0035-1552620. PMID: 26060909
Zupanc ML, Legros B
Cerebellum 2004;3(3):156-71. doi: 10.1080/14734220410035356. PMID: 15543806

Diagnosis

Dang Do AN, Baker EH, Farmer CA, Soldatos AG, Thurm AE, Porter FD
Mol Genet Metab 2023 May;139(1):107584. Epub 2023 Apr 15 doi: 10.1016/j.ymgme.2023.107584. PMID: 37086568Free PMC Article
Deneubourg C, Ramm M, Smith LJ, Baron O, Singh K, Byrne SC, Duchen MR, Gautel M, Eskelinen EL, Fanto M, Jungbluth H
Autophagy 2022 Mar;18(3):496-517. Epub 2021 Aug 19 doi: 10.1080/15548627.2021.1943177. PMID: 34130600Free PMC Article
Johnson TB, Cain JT, White KA, Ramirez-Montealegre D, Pearce DA, Weimer JM
Nat Rev Neurol 2019 Mar;15(3):161-178. doi: 10.1038/s41582-019-0138-8. PMID: 30783219Free PMC Article
Kälviäinen R
Semin Neurol 2015 Jun;35(3):293-9. Epub 2015 Jun 10 doi: 10.1055/s-0035-1552620. PMID: 26060909
Bennett MJ, Rakheja D
Dev Disabil Res Rev 2013;17(3):254-9. doi: 10.1002/ddrr.1118. PMID: 23798013

Therapy

Rodriguez-Martinez AC, Wawrzynski J, Henderson RH
Curr Opin Ophthalmol 2024 May 1;35(3):232-237. Epub 2023 Dec 26 doi: 10.1097/ICU.0000000000001029. PMID: 38170785
Schulz A, Specchio N, de Los Reyes E, Gissen P, Nickel M, Trivisano M, Aylward SC, Chakrapani A, Schwering C, Wibbeler E, Westermann LM, Ballon DJ, Dyke JP, Cherukuri A, Bondade S, Slasor P, Cohen Pfeffer J
Lancet Neurol 2024 Jan;23(1):60-70. doi: 10.1016/S1474-4422(23)00384-8. PMID: 38101904
Dang Do AN, Baker EH, Farmer CA, Soldatos AG, Thurm AE, Porter FD
Mol Genet Metab 2023 May;139(1):107584. Epub 2023 Apr 15 doi: 10.1016/j.ymgme.2023.107584. PMID: 37086568Free PMC Article
Vasquez A, Farias-Moeller R, Sánchez-Fernández I, Abend NS, Amengual-Gual M, Anderson A, Arya R, Brenton JN, Carpenter JL, Chapman K, Clark J, Gaillard WD, Glauser T, Goldstein JL, Goodkin HP, Guerriero RM, Lai YC, McDonough TL, Mikati MA, Morgan LA, Novotny EJ, Ostendorf AP, Payne ET, Peariso K, Piantino J, Riviello JJ, Sands TT, Sannagowdara K, Tasker RC, Tchapyjnikov D, Topjian A, Wainwright MS, Wilfong A, Williams K, Loddenkemper T; Pediatric Status Epilepticus Research Group (pSERG)
Pediatr Crit Care Med 2021 Dec 1;22(12):e613-e625. doi: 10.1097/PCC.0000000000002786. PMID: 34120133
Benes P, Vetvicka V, Fusek M
Crit Rev Oncol Hematol 2008 Oct;68(1):12-28. Epub 2008 Apr 8 doi: 10.1016/j.critrevonc.2008.02.008. PMID: 18396408Free PMC Article

Prognosis

Deneubourg C, Ramm M, Smith LJ, Baron O, Singh K, Byrne SC, Duchen MR, Gautel M, Eskelinen EL, Fanto M, Jungbluth H
Autophagy 2022 Mar;18(3):496-517. Epub 2021 Aug 19 doi: 10.1080/15548627.2021.1943177. PMID: 34130600Free PMC Article
Canafoglia L, Gilioli I, Invernizzi F, Sofia V, Fugnanesi V, Morbin M, Chiapparini L, Granata T, Binelli S, Scaioli V, Garavaglia B, Nardocci N, Berkovic SF, Franceschetti S
Neurology 2015 Jul 28;85(4):316-24. Epub 2015 Jun 26 doi: 10.1212/WNL.0000000000001784. PMID: 26115733Free PMC Article
Kälviäinen R
Semin Neurol 2015 Jun;35(3):293-9. Epub 2015 Jun 10 doi: 10.1055/s-0035-1552620. PMID: 26060909
Wisniewski KE, Kida E, Connell F, Zhong N
Neurol Sci 2000;21(3 Suppl):S49-56. doi: 10.1007/s100720070040. PMID: 11073228
Berkovic SF, So NK, Andermann F
J Clin Neurophysiol 1991 Jul;8(3):261-74. PMID: 1918332

Clinical prediction guides

Schulz A, Specchio N, de Los Reyes E, Gissen P, Nickel M, Trivisano M, Aylward SC, Chakrapani A, Schwering C, Wibbeler E, Westermann LM, Ballon DJ, Dyke JP, Cherukuri A, Bondade S, Slasor P, Cohen Pfeffer J
Lancet Neurol 2024 Jan;23(1):60-70. doi: 10.1016/S1474-4422(23)00384-8. PMID: 38101904
Klein M, Kaleem A, Oetjen S, Wünkhaus D, Binkle L, Schilling S, Gjorgjieva M, Scholz R, Gruber-Schoffnegger D, Storch S, Kins S, Drewes G, Hoffmeister-Ullerich S, Kuhl D, Hermey G
Autophagy 2022 Sep;18(9):2068-2085. Epub 2021 Dec 29 doi: 10.1080/15548627.2021.2016232. PMID: 34964690Free PMC Article
Ju W, Wronska A, Moroziewicz DN, Zhong R, Wisniewski N, Jurkiewicz A, Fiory M, Wisniewski KE, Johnston L, Brown WT, Zhong N
Beijing Da Xue Xue Bao Yi Xue Ban 2006 Feb 18;38(1):41-8. PMID: 16415965
Glaser RL, Hickey AJ, Chotkowski HL, Chu-LaGraff Q
Gene 2003 Jul 17;312:271-9. doi: 10.1016/s0378-1119(03)00623-1. PMID: 12909364
Wisneiwski KE, Kida E, Patxot OF, Connell F
Am J Med Genet 1992 Feb 15;42(4):525-32. doi: 10.1002/ajmg.1320420420. PMID: 1319116

Recent systematic reviews

Quintas S, Sanles-Falagan R, Berbís MÁ
Mov Disord Clin Pract 2024 Jun;11(6):613-625. Epub 2024 May 1 doi: 10.1002/mdc3.14055. PMID: 38693679Free PMC Article
Yoganathan S, Whitney R, Thomas M, Danda S, Chettali AM, Prasad AN, Farhan SMK, AlSowat D, Abukhaled M, Aldhalaan H, Gowda VK, Kinhal UV, Bylappa AY, Konanki R, Lingappa L, Parchuri BM, Appendino JP, Scantlebury MH, Cunningham J, Hadjinicolaou A, El Achkar CM, Kamate M, Menon RN, Jose M, Riordan G, Kannan L, Jain V, Manokaran RK, Chau V, Donner EJ, Costain G, Minassian BA, Jain P
Epilepsia 2024 Mar;65(3):709-724. Epub 2024 Jan 17 doi: 10.1111/epi.17880. PMID: 38231304
Parvin S, Rezazadeh M, Hosseinzadeh H, Moradi M, Shiva S, Gharesouran J
Neuromolecular Med 2019 Jun;21(2):160-169. Epub 2019 Mar 27 doi: 10.1007/s12017-019-08529-7. PMID: 30919163

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