Registry Gangliosidoses

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

             -  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

      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

      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


        -  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



Study Arms / Comparison Groups

 GM1-Gangliosidosis - Sialidosis
Description:  Confirmed diagnosis of:
GM1-Gangliosidosis Morquio B Variant


* 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


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.




N/A - N/A

Accepts Healthy Volunteers



, 0496146904820, [email protected]

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party


Study Sponsor

SphinCS Lyso Gemeinnutzige UG (Haftungsbeschrankt)

Study Sponsor

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Verification Date

October 2020