Brief Title
Registry Gangliosidoses
Official Title
Eight At One Stroke: Attention Gangliosidoses A Registry Study for Patients With Gangliosidoses
Brief Summary
The clinical project "Eight At One Stroke: Attention Gangliosidoses" represents a clinical
registry for recording the clinical manifestation and the disease progression of
gangliosidoses. The intention of this project is to better understand the manifestation and
progression of gangliosidoses and to raise awareness of these disorders in the public health
service. The patients or their families, respectively, will be integrated in the study in
order to measure Patient Outcome and to objectify the psychosocial burden for the patient and
his family. The study has a retrospective and a prospective part. It is planned to transfer
the data of the study into a continuous registry.
Detailed Description
1. Aim of the Project
- The aim of the project is to collect fundamental epidemiological and clinical data,
such as prevalence and incidence, but also data regarding phenotype, diagnosis and
mutation spectrum.
- To understand the natural course of these diseases seems to be very important for
individual advice of families and additionally for planning drug studies.
- In this study it should also be analyzed how the families and their setting have
perceived the disease manifestation. Their perception will be compared to clinical
findings and symptoms that were noticed by the physician. The medical history may
indicate which symptoms and findings may lead to a well-directed diagnosis.
- Clinical and genetic data, that also concern aspects of social medicine, of a
greater cohort will raise the awareness of pharmaceutical companies that develop
new drugs and will increase the chance of patients to participate in a clinical
trial.
- The project will enable validation of biomarkers that may be useful for diagnostic
purposes and also for monitoring laboratory parameters during a trial.
- Patients and their families are involved in the development and procedure of the
study. They become a voice and are noticed as partners in the public health
service.
3. Background 3.1 Gangliosidoses Gangliosidoses represent autosomal-recessive lysosomal
storage disorders, caused by a defect in the lysosomal degradation of gangliosides, resulting
in accumulation of these substrates in several organs. Gangliosidoses are divided in eight
different diseases according to their biochemical and genetic defect: Four disorders are
assigned to GM2-Gangliosidoses, four belong to the Neuraminidase-ß-Galactosidase complex.
Gangliosidoses are characterized by more or less pronounced progressive loss of mental and
motor capabilities. In patients with a more attenuated phenotype the diagnosis is done often
very late, as the typical clinical "classical" features are commonly lacking. Maybe adult
patients were never diagnosed.
The diseases result from the accumulation of gangliosides, caused by genetic defects of
enzymes or other proteins that are involved in the lysosomal degradation of these complex
lipids.
3.2 Classification of Gangliosides GM1-Gangliosidosis - Sialidosis
- GM1-Gangliosidosis (1) Morquio B Variant (2) ß-Galactosidase
- Sialidosis (3) Neuraminidase
- Galactosialidosis (4) Protective Protein/Cathepsin A
GM2-Gangliosidoses
- Tay-Sachs Disease (5), incl. B1-Variante (6) Hexosaminidase A
- Sandhoff Disease (7) Hexosamidase A&B
- GM2-Activator-Deficiency (8) GM2-activator-protein
3.3 Clinical Phenotypes The degree of clinical expression regarding the age of first
manifestation, rate of progression and symptoms is extremely heterogeneous and reaches from
the lethal hydrops fetalis to the rapidly progressive and to the slowly progressive adult
form. The underlying mutations determine the enzyme respectively protein deficiency, in the
more attenuated forms, however, the phenotype is additionally influenced by epigenetic
factors and the environment. Generally five phenotypic forms are distinguished that differ in
the age of first symptoms.
Hydrops fetalis Gangliosidoses can manifest as hydrops fetalis that is defined as fetal fluid
accumulation in at least two organ systems, such as ascites, pleural and pericardium effusion
and generalized edema. Hydrops fetalis, that mostly leads to intrauterine death, was
surprisingly not observed in GM2-gangliosidoses.
Infantile Gangliosidoses Patients with the so-called "classical" infantile form manifest
after birth with developmental delay. Between the age of three to six months significant
muscular hypotonia becomes obvious. Often, but not exclusively, in GM2-gangliosidoses the
parents observe as first symptom an excessive response to an acoustic stimulus with sudden
hyperextension of arms and legs and muscle jerks. A cherry-red spot at the eye fundus and a
macrocephaly may lead to the diagnosis. A so-called "Hurler-phenotype" is seen in infants
with sialidosis, galactosialidosis and GM1-gangliosidoses.
Late-infantile and juvenile Gangliosidoses It is often not possible to differentiate between
late.infantile and juvenile gangliosidoses: In young children the parents observe deficits in
motor and speech development, later these capabilities get lost. The occurrence of epilpetic
seizures implies a bad prognosis. In GM2-gangliosidoses the tetraparesis is hypotonic and
floppy, in GM1-gangliosidoses dystonic and spastic. The progressive visual impairment can
result in blindness.
Late-onset Gangliosidoses Patients with late-onset (or chronic-adult) type of gangliosidoses
present with cerebellar signs such as ataxia, dysarthria and hypotonia. Late-onset
GM2-gangliosidoses are characterized by intention tremor and dysmetria, in late-onset
GM1-gangliosidoses dystonia and spasticity are the leading neurological symptoms. Prior to
the occurrence of neurological symptoms psychoses and episodes of psychosis may appear that
later on may dominate the disease manifestation. The cognitive abilities are hardly impaired,
due to the severe dysarthria, however, it may be difficult to correctly evaluate the
cognitive function. Because in adult gangliosidoses the motor neuron is involved, the
patients may resemble individuals with Friedreich-Ataxia ot SMA, for which reason a
differentiation between thoMedise disorders may be difficult
Study Type
Observational [Patient Registry]
Primary Outcome
Disease progression will be assessed by the 8 in 1 score
Secondary Outcome
Characterization of the first neurological symptom
Condition
Gangliosidoses
Study Arms / Comparison Groups
GM1-Gangliosidosis - Sialidosis
Description: Confirmed diagnosis of: GM1-Gangliosidosis Morquio B Variant Sialidosis Galactosialidosis
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Estimated Enrollment
40
Start Date
June 8, 2020
Completion Date
June 7, 2025
Primary Completion Date
June 12, 2020
Eligibility Criteria
Inclusion Criteria:
- Biochemically and/or genetically affirmed diagnosis of a gangliosidosis
- The patient or respectively the parents or the caregiver (for children or older
underage patients) have given written informed consent
Exclusion Criteria:
- The diagnosis of a gangliosidosis has not biochemically or genetically confirmed.
- A written informed consent of the patient or parents/acaregiver does not exist.
Gender
All
Ages
N/A - N/A
Accepts Healthy Volunteers
No
Contacts
, 0496146904820, [email protected]
Location Countries
Germany
Location Countries
Germany
Administrative Informations
NCT ID
NCT04624789
Organization ID
D001
Responsible Party
Sponsor
Study Sponsor
SphinCS Lyso Gemeinnutzige UG (Haftungsbeschrankt)
Study Sponsor
, ,
Verification Date
October 2020