Lysomal Storage Disorder

The Mole

GM2-Gangliosidosis

GM2-Gangliosidosis can be caused by a deficiency of hexosaminidase A (Tay-Sachs disease), or of hexosaminidases A and B (Sandhoff disease) or of GM2 activator protein (GM2 activator defect). Based on clinical features, the diseases cannot be distinguished. In the classic clinical picture, a pronounced sensitivity to noise is noticeable in the very first months of life. Loud noises such as closing doors or clapping hands lead to Moro-like motor manifestations. Already before the 6th month of life the motor development is limited. The diagnosis is often made because a cherry red spot is found during the ophthalmological examination. The infants are hypotonic, have poor head control. Verticalisation is delayed. A macrocephalus develops. At the beginning of the second year of life, the infants lose again their laboriously acquired abilities as well as vocalization and become blind. As a rule, the course is complicated by an epilepsy that is difficult to treat. Non-classical forms of the disease - described as juvenile or adult forms - are difficult to diagnose because the classic features are missing. The main findings in attenuated forms of epilepsy are motor developmental disorders and seizures with and without myoclonies in childhood, adolescence and young adulthood, a combination of psychosis (often delusional), ataxia and distal paresis (motor neuron disease as in Friedreich's ataxia).  

GM2-Gangliosidosis | SphinCS - Clinical Science for LSD

Tay-Sachs Disease

Etiology: Deficiency of hexosaminidase A
Gene: HEXA Gene
Mode of inheritance: Autosomal recessive
Phenotypes:

  • Infantile form 
  • Juvenile form 
  • Adult form 

Leitsymptome:

Infantile form
(Age of onset: 3 -6 months)

  • Startle responses
  • Psychomotor retardation
  • Muscular hypotonia
  • Macrozephalus
  • Cherry red spot
  • Vision disorder/ blindness

Juvenile form
(Age of onset:  2-6 years)

  • Gait ataxia
  • Cognitive decline
  • Epilepsy
  • Dystonia
  • Vision disorder/ blindness

Adult form
(Manifestationsalter: ab ca. 10. Lebensjahr)

  • Ataxia
  • Intention tremor
  • Muscle weakness
  • Myoklonus
  • Psychosis/ depression

Diagnostics:

  • Measurement of the activity of hexosaminidase A in plasma or serum
  • Molecular genetic analysis of HEXA Gene

Therapy:
Only symptomatic

Sandhoff Disease

Etiology: Deficiency of hexosaminidase B and hexosaminidase A/B
Gene: HEXB-Gene
Mode of inheritance: Autosomal recessive
Phenotypes:

  • Infantile form 
  • Juvenile form 
  • Adulte form 

Leading symptoms:

Infantile form
(Age of onset: 3-6 months)

  • Startle responses
  • Psychomotor retardation
  • Muscular hypotonia
  • Macrocephalus
  • Cherry red spot
  • Vision disorder/ blindness

Juvenile form
(Age of onset: 2-6 years)

  • Ataxia
  • Cognitive decline
  • Psychomotor development delay/ arrest 
  • Dystonia
  • Epilepsy
  • Vision disorder/ blindness

Adult form
(Age of onset: ≥ 10 years)

  • Ataxia
  • Intention tremor
  • Muscular weakness
  • Myoklonus
  • Psychosis/ depression

Diagnostics:

  • Measurement of the activity of hexosaminidase B und hexosaminidase A/B
  • Molecular genetic analysis of HEXB Gene

Therapy:
Only symptomatic

Activator-Deficiency

Synonym: GM2-Gangliosidosis AB Variant
Etiology: Deficiency of GM2-activator
Gene: GM2A Gene
Mode of inheritance: Autosomal recessive
Phenotypes: Like GM2-Gangliosidosis
Leading symptoms: Like GM2-Gangliosidosis
Diagnostics: Molecular genetic analysis of GM2A Gene
Therapy: Only symptomatic

Current Studies

Gaucher Disease GM1-Gangliosidosis GM2-Gangliosidosis
Retrieve
Natural history study for pediatric parents with early onset of either GM1 gangliosidoses, GM 2 gangliosidoses, or Gaucher disease typ 2
Age

Birthdate after or at 1 of january 2000

Status active

Patient admission recruiting

Institution SphinCS GmbH

Natural-History-Study
GM1-Gangliosidosis GM2-Gangliosidosis
Gangliosidosis „8 in 1“
This is a retrospective and prospective and longitudinal, non-interventional study on the natural course of gangliosidoseovers over 5 years
Age

No age limit

Status active

Patient admission recruiting

Institution SphinCS Lyso gemeinnützige UG (haftungsbeschränkt)

Register-Study
The "U.S. National Library of Medicine" provides a complete list of all international studies at www.clinicaltrials.gov. The comparable EU website is less comprehensive: www.clinicaltrialsregister.eu.

Self-help groups

Hand in Hand gegen Tay-Sachs und Sandhoff in Deutschland e.V.
http://tay-sachs-sandhoff.de/

At the moment we are not aware of any self-help groups.

Literature

At present we have no literature available.