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Gangliosidosis GM1 type 3

MedGen UID:
78655
Concept ID:
C0268273
Disease or Syndrome
Synonyms: Adult GM1 gangliosidosis; Beta-galactosidase deficiency; GANGLIOSIDOSIS, GENERALIZED GM1, ADULT TYPE; GANGLIOSIDOSIS, GENERALIZED GM1, CHRONIC TYPE; Gangliosidosis, Generalized GM1, Type 3; GANGLIOSIDOSIS, GENERALIZED GM1, TYPE III; GM1-GANGLIOSIDOSIS, TYPE III; Type 3 (adult) GM1 gangliosidosis
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: HPO
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
SNOMED CT: Adult GM>1< gangliosidosis (73855005); GM>1< gangliosidosis, type 3 (73855005); Adult GM1 gangliosidosis (238027003); GM1 Gangliosidosis type III (238027003)
 
Gene (location): GLB1 (3p22.3)
OMIM®: 230650
Orphanet: ORPHA79257

Definition

GM1-gangliosidosis type III is an autosomal recessive lysosomal storage disorder characterized by neurodegeneration and mild skeletal changes. Age at onset ranges from 3 to 30 years. The disorder is less severe than GM1-gangliosidosis types I and II (230600). Type III shows extreme clinical variability, with some patients having only focal neurologic signs, such as dystonia, and others having more severe involvement with extrapyramidal signs and mental retardation. GLB1 enzymatic activity usually ranges from approximately 4 to 10% of control values (Suzuki et al., 2001). [from OMIM]

Additional description

From GHR
GM1 gangliosidosis is an inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. Some researchers classify this condition into three major types based on the age at which signs and symptoms first appear. Although the three types differ in severity, their features can overlap significantly. Because of this overlap, other researchers believe that GM1 gangliosidosis represents a continuous disease spectrum instead of three distinct types. The signs and symptoms of the most severe form of GM1 gangliosidosis, called type I or the infantile form, usually become apparent by the age of 6 months. Infants with this form of the disorder typically appear normal until their development slows and muscles used for movement weaken. Affected infants eventually lose the skills they had previously acquired (developmentally regress) and may develop an exaggerated startle reaction to loud noises. As the disease progresses, children with GM1 gangliosidosis type I develop an enlarged liver and spleen (hepatosplenomegaly), skeletal abnormalities, seizures, profound intellectual disability, and clouding of the clear outer covering of the eye (the cornea). Loss of vision occurs as the light-sensing tissue at the back of the eye (the retina) gradually deteriorates. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. In some cases, affected individuals have distinctive facial features that are described as "coarse," enlarged gums (gingival hypertrophy), and an enlarged and weakened heart muscle (cardiomyopathy). Individuals with GM1 gangliosidosis type I usually do not survive past early childhood. Type II GM1 gangliosidosis consists of intermediate forms of the condition, also known as the late infantile and juvenile forms. Children with GM1 gangliosidosis type II have normal early development, but they begin to develop signs and symptoms of the condition around the age of 18 months (late infantile form) or 5 years (juvenile form). Individuals with GM1 gangliosidosis type II experience developmental regression but usually do not have cherry-red spots, distinctive facial features, or enlarged organs. Type II usually progresses more slowly than type I, but still causes a shortened life expectancy. People with the late infantile form typically survive into mid-childhood, while those with the juvenile form may live into early adulthood. The third type of GM1 gangliosidosis is known as the adult or chronic form, and it represents the mildest end of the disease spectrum. The age at which symptoms first appear varies in GM1 gangliosidosis type III, although most affected individuals develop signs and symptoms in their teens. The characteristic features of this type include involuntary tensing of various muscles (dystonia) and abnormalities of the spinal bones (vertebrae). Life expectancy varies among people with GM1 gangliosidosis type III.  http://ghr.nlm.nih.gov/condition/gm1-gangliosidosis

Clinical features

Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
Cherry red spot of the macula
MedGen UID:
786046
Concept ID:
C2216370
Finding
Abnormality of the face
MedGen UID:
446344
Concept ID:
CN000257
Finding
An abnormality of the face.
Opacification of the corneal stroma
MedGen UID:
347281
Concept ID:
C1856661
Finding
Cherry red spot of the macula
MedGen UID:
786046
Concept ID:
C2216370
Finding
Slurred speech
MedGen UID:
65885
Concept ID:
C0234518
Finding
Seizures
MedGen UID:
409523
Concept ID:
C1959629
Finding
Intellectual disability, mild
MedGen UID:
504770
Concept ID:
CN001151
Finding
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Dystonia
MedGen UID:
504804
Concept ID:
CN001220
Finding
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.
Myoclonus
MedGen UID:
504806
Concept ID:
CN001224
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Diffuse cerebral atrophy
MedGen UID:
505256
Concept ID:
CN002277
Finding
Diffuse unlocalised atrophy affecting the cerebrum.
Kyphosis
MedGen UID:
335104
Concept ID:
C1845112
Finding
Hypoplastic acetabulae
MedGen UID:
375890
Concept ID:
C1846442
Finding
Platyspondyly
MedGen UID:
355353
Concept ID:
C1865023
Finding
Flared iliac wings
MedGen UID:
356097
Concept ID:
C1865841
Finding
Scoliosis
MedGen UID:
427922
Concept ID:
CN002409
Finding
The presence of an abnormal lateral curvature of the spine.
Anterior beaking of lumbar vertebrae
MedGen UID:
506224
Concept ID:
CN007416
Finding
Anterior tongue-like protrusions of the vertebral bodies of the lumbar spine.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Hepatomegaly
MedGen UID:
505165
Concept ID:
CN002031
Finding
Abnormally increased size of the liver.
Cherry red spot of the macula
MedGen UID:
786046
Concept ID:
C2216370
Finding
Foam cells
MedGen UID:
446499
Concept ID:
CN003299
Finding
The presence of foam cells, which cells in an atheroma that can be derived from either macrophages or smooth muscle cells that have taken up modified low density lipoprotein particles and thereby take on a foamy appearance.
Abnormality of blood and blood-forming tissues
MedGen UID:
504979
Concept ID:
CN001691
Finding
An abnormality of the hematopoietic system.
Decreased beta-galactosidase activity
MedGen UID:
446897
Concept ID:
CN007172
Finding
Abnormally decreased rate of beta-galactosidase activity.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Skeletal muscle atrophy
MedGen UID:
505481
Concept ID:
CN002890
Finding
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Hypoplastic acetabulae
MedGen UID:
375890
Concept ID:
C1846442
Finding

Recent clinical studies

Etiology

King JE, Dexter A, Gadi I, Zvereff V, Martin M, Bloom M, Vanderver A, Pizzino A, Schmidt JL
J Genet Couns 2014 Oct;23(5):734-41. Epub 2014 Apr 30 doi: 10.1007/s10897-014-9720-9. [Epub ahead of print] PMID: 24777551
Suzuki Y
Brain Dev 2013 Jun;35(6):515-23. Epub 2013 Jan 3 doi: 10.1016/j.braindev.2012.12.002. [Epub ahead of print] PMID: 23290321
Sperb F, Vairo F, Burin M, Mayer FQ, Matte U, Giugliani R
Gene 2013 Jan 1;512(1):113-6. Epub 2012 Oct 6 doi: 10.1016/j.gene.2012.09.106. [Epub ahead of print] PMID: 23046582
Fantur KM, Wrodnigg TM, Stütz AE, Pabst BM, Paschke E
J Inherit Metab Dis 2012 May;35(3):495-503. Epub 2011 Oct 28 doi: 10.1007/s10545-011-9409-2. [Epub ahead of print] PMID: 22033734
Fröhlich RF, Furneaux RH, Mahuran DJ, Saf R, Stütz AE, Tropak MB, Wicki J, Withers SG, Wrodnigg TM
Carbohydr Res 2011 Sep 6;346(12):1592-8. Epub 2011 May 24 doi: 10.1016/j.carres.2011.05.010. [Epub ahead of print] PMID: 21645885Free PMC Article

Diagnosis

Takenouchi T, Kosaki R, Nakabayashi K, Hata K, Takahashi T, Kosaki K
Pediatr Neurol 2015 Feb;52(2):226-9. Epub 2014 Oct 16 doi: 10.1016/j.pediatrneurol.2014.09.022. [Epub ahead of print] PMID: 25443580
King JE, Dexter A, Gadi I, Zvereff V, Martin M, Bloom M, Vanderver A, Pizzino A, Schmidt JL
J Genet Couns 2014 Oct;23(5):734-41. Epub 2014 Apr 30 doi: 10.1007/s10897-014-9720-9. [Epub ahead of print] PMID: 24777551
Vieira JP, Conceição C, Scortenschi E
Pediatr Neurol 2013 Sep;49(3):195-7. Epub 2013 Jul 4 doi: 10.1016/j.pediatrneurol.2013.02.003. [Epub ahead of print] PMID: 23831247
Sperb F, Vairo F, Burin M, Mayer FQ, Matte U, Giugliani R
Gene 2013 Jan 1;512(1):113-6. Epub 2012 Oct 6 doi: 10.1016/j.gene.2012.09.106. [Epub ahead of print] PMID: 23046582
Lei HL, Ye J, Qiu WJ, Zhang HW, Han LS, Wang Y, Gu XF
World J Pediatr 2012 Nov;8(4):359-62. Epub 2012 Nov 15 doi: 10.1007/s12519-012-0382-0. [Epub ahead of print] PMID: 23151865

Therapy

Siriwardena A, Sonawane DP, Bande OP, Markad PR, Yonekawa S, Tropak MB, Ghosh S, Chopade BA, Mahuran DJ, Dhavale DD
J Org Chem 2014 May 16;79(10):4398-404. Epub 2014 Apr 28 doi: 10.1021/jo500328u. [Epub ahead of print] PMID: 24735108
Suzuki Y
Brain Dev 2013 Jun;35(6):515-23. Epub 2013 Jan 3 doi: 10.1016/j.braindev.2012.12.002. [Epub ahead of print] PMID: 23290321
Rigat BA, Tropak MB, Buttner J, Crushell E, Benedict D, Callahan JW, Martin DR, Mahuran DJ
Mol Genet Metab 2012 Sep;107(1-2):203-12. Epub 2012 Jun 19 doi: 10.1016/j.ymgme.2012.06.007. [Epub ahead of print] PMID: 22784478Free PMC Article
Suzuki Y, Ichinomiya S, Kurosawa M, Matsuda J, Ogawa S, Iida M, Kubo T, Tabe M, Itoh M, Higaki K, Nanba E, Ohno K
Mol Genet Metab 2012 May;106(1):92-8. Epub 2012 Mar 3 doi: 10.1016/j.ymgme.2012.02.012. [Epub ahead of print] PMID: 22436580
Georgiou T, Stylianidou G, Anastasiadou V, Caciotti A, Campos Y, Zammarchi E, Morrone A, D'azzo A, Drousiotou A
Genet Test 2005 Summer;9(2):126-32. doi: 10.1089/gte.2005.9.126. PMID: 15943552

Prognosis

Takenouchi T, Kosaki R, Nakabayashi K, Hata K, Takahashi T, Kosaki K
Pediatr Neurol 2015 Feb;52(2):226-9. Epub 2014 Oct 16 doi: 10.1016/j.pediatrneurol.2014.09.022. [Epub ahead of print] PMID: 25443580
Lei HL, Ye J, Qiu WJ, Zhang HW, Han LS, Wang Y, Gu XF
World J Pediatr 2012 Nov;8(4):359-62. Epub 2012 Nov 15 doi: 10.1007/s12519-012-0382-0. [Epub ahead of print] PMID: 23151865
Pierson TM, Adams DA, Markello T, Golas G, Yang S, Sincan M, Simeonov DR, Fuentes Fajardo K, Hansen NF, Cherukuri PF, Cruz P, Teer JK, Mullikin JC; NISC Comparative Sequencing Program, Boerkoel CF, Gahl WA, Tifft CJ
Neurology 2012 Jul 10;79(2):123-6. Epub 2012 Jun 6 doi: 10.1212/WNL.0b013e31825f047a. [Epub ahead of print] PMID: 22675082Free PMC Article
Caciotti A, Garman SC, Rivera-Colón Y, Procopio E, Catarzi S, Ferri L, Guido C, Martelli P, Parini R, Antuzzi D, Battini R, Sibilio M, Simonati A, Fontana E, Salviati A, Akinci G, Cereda C, Dionisi-Vici C, Deodato F, d'Amico A, d'Azzo A, Bertini E, Filocamo M, Scarpa M, di Rocco M, Tifft CJ, Ciani F, Gasperini S, Pasquini E, Guerrini R, Donati MA, Morrone A
Biochim Biophys Acta 2011 Jul;1812(7):782-90. Epub 2011 Apr 7 doi: 10.1016/j.bbadis.2011.03.018. [Epub ahead of print] PMID: 21497194Free PMC Article
Hofer D, Paul K, Fantur K, Beck M, Roubergue A, Vellodi A, Poorthuis BJ, Michelakakis H, Plecko B, Paschke E
Clin Genet 2010 Sep;78(3):236-46. Epub 2010 Feb 11 doi: 10.1111/j.1399-0004.2010.01379.x. [Epub ahead of print] PMID: 20175788

Clinical prediction guides

Takenouchi T, Kosaki R, Nakabayashi K, Hata K, Takahashi T, Kosaki K
Pediatr Neurol 2015 Feb;52(2):226-9. Epub 2014 Oct 16 doi: 10.1016/j.pediatrneurol.2014.09.022. [Epub ahead of print] PMID: 25443580
Sperb F, Vairo F, Burin M, Mayer FQ, Matte U, Giugliani R
Gene 2013 Jan 1;512(1):113-6. Epub 2012 Oct 6 doi: 10.1016/j.gene.2012.09.106. [Epub ahead of print] PMID: 23046582
Lei HL, Ye J, Qiu WJ, Zhang HW, Han LS, Wang Y, Gu XF
World J Pediatr 2012 Nov;8(4):359-62. Epub 2012 Nov 15 doi: 10.1007/s12519-012-0382-0. [Epub ahead of print] PMID: 23151865
Pierson TM, Adams DA, Markello T, Golas G, Yang S, Sincan M, Simeonov DR, Fuentes Fajardo K, Hansen NF, Cherukuri PF, Cruz P, Teer JK, Mullikin JC; NISC Comparative Sequencing Program, Boerkoel CF, Gahl WA, Tifft CJ
Neurology 2012 Jul 10;79(2):123-6. Epub 2012 Jun 6 doi: 10.1212/WNL.0b013e31825f047a. [Epub ahead of print] PMID: 22675082Free PMC Article
Caciotti A, Garman SC, Rivera-Colón Y, Procopio E, Catarzi S, Ferri L, Guido C, Martelli P, Parini R, Antuzzi D, Battini R, Sibilio M, Simonati A, Fontana E, Salviati A, Akinci G, Cereda C, Dionisi-Vici C, Deodato F, d'Amico A, d'Azzo A, Bertini E, Filocamo M, Scarpa M, di Rocco M, Tifft CJ, Ciani F, Gasperini S, Pasquini E, Guerrini R, Donati MA, Morrone A
Biochim Biophys Acta 2011 Jul;1812(7):782-90. Epub 2011 Apr 7 doi: 10.1016/j.bbadis.2011.03.018. [Epub ahead of print] PMID: 21497194Free PMC Article

Recent systematic reviews

Gimovsky AC, Luzi P, Berghella V
Am J Obstet Gynecol 2015 Mar;212(3):281-90. Epub 2014 Oct 8 doi: 10.1016/j.ajog.2014.10.007. [Epub ahead of print] PMID: 25305402
Caciotti A, Garman SC, Rivera-Colón Y, Procopio E, Catarzi S, Ferri L, Guido C, Martelli P, Parini R, Antuzzi D, Battini R, Sibilio M, Simonati A, Fontana E, Salviati A, Akinci G, Cereda C, Dionisi-Vici C, Deodato F, d'Amico A, d'Azzo A, Bertini E, Filocamo M, Scarpa M, di Rocco M, Tifft CJ, Ciani F, Gasperini S, Pasquini E, Guerrini R, Donati MA, Morrone A
Biochim Biophys Acta 2011 Jul;1812(7):782-90. Epub 2011 Apr 7 doi: 10.1016/j.bbadis.2011.03.018. [Epub ahead of print] PMID: 21497194Free PMC Article
Autti T, Joensuu R, Aberg L
Neuroradiology 2007 Jul;49(7):571-8. Epub 2007 Mar 3 doi: 10.1007/s00234-007-0220-6. [Epub ahead of print] PMID: 17334752
Roze E, Paschke E, Lopez N, Eck T, Yoshida K, Maurel-Ollivier A, Doummar D, Caillaud C, Galanaud D, Billette de Villemeur T, Vidailhet M, Roubergue A
Mov Disord 2005 Oct;20(10):1366-9. doi: 10.1002/mds.20593. PMID: 15986423
Haust MD
Am J Cardiovasc Pathol 1987;1(2):231-85. PMID: 3333142

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