Patients with GM1/GM2-Gangliosidosis or high-grade suspicion for GM1/GM2-Gangliosidosis

For the development of the new biomarkers using the technique of Mass-spectometry, maximal 10 ml blood will be taken via using a dry blood spot filter card. To proof the cor-rect GM1/GM2 diagnosis in those patients where up to the enrollment into the study no genetic testing has been done, sequencing of GM1/GM2 will be done. The analyses will be done at the Centogene AG Am Strande 7 18055 Rostock Germany

Hepato-splenomegaly

Dysostosis Multiplex

Seizures

Mental Retardation

Centogene is one of the leading laboratories focusing on genetic testing for rare hereditary disorders. We now offer more than 2200 routine genetic and biochemical tests.

Children's Hospital, Faculty of Medicine, Ain Shams University

Centogene AG

Amrita Institute of Medical Sciences & Research Centre

Navi Mumbai Institute of Research In Mental And Neurological Handicap (NIRMAN)

Lady Ridgeway Hospital for Children

Biomarker for Gangliosidosis: BioGM1/BioGM2 (BioGM1/GM2)

Biomarker for Gangliosidosis: BioGM1 / BioGM2 AN INTERNATIONAL, MULTICENTER, EPIDEMIOLOGICAL PROTOCOL

New methods, like mass-spectrometry give a good chance to characterize specific metabolic alterations in the blood of affected patients that allow diagnosing in the future the disease earlier, with a higher sensitivity and specificity.

the goal of the study to identify and validate a new biochemical marker from the blood of the affected patients helping to benefit other patients by an early diagnose and thereby with an earlier treatment.

Centogene AG Rostock

These patients were randomized to receive the placebo in Phase A and study drug (NAC) in Phase B of the trial

Placebo Phase A/NAC Phase B

These patients were randomized to receive study drug (NAC) in Phase A and placebo in Phase B

NAC Phase A/Placebo Phase B

Total

Sex: Female, Male

Region of Enrollment

NAC Phase

Placebo Phase

Oxysterol Levels

Overall Study

Dr. Forbes D Porter, Senior Investigator

Niemann-Pick Disease, Type C

900mg effervescent tablet; Dosed as 15 mg/kg/day (maximum dose 900 mg per day) for one week, advanced to 30 mg/kg/day (maximum dose 1800 mg per day) for the second week, and then advanced to 60 mg/kg/day (maximum dose 2700 mg) for the remainder of the trial (6 additional weeks).

N-Acetyl Cysteine

National Institutes of Health Clinical Center, 9000 Rockville Pike

Biomarker Validation for Niemann-Pick Disease, Type C: Safety and Efficacy of N-Acetyl Cysteine

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

University of Oxford

Washington University School of Medicine

National Human Genome Research Institute (NHGRI)

Single arm study involving oral administration of valproic acid and monitoring of its efficacy by CT scans done before and after the intervention. Blood samples were also obtained to monitor safety labs and biomarkers.

valproic acid administered starting at 10 mg/kg/day in divided doses twice daily x 3 days, increase to 15mg/kg/day x 3 days, increase to 20 mg/kg/day on day 7, increase to 30 mg/kg/day on day 14, maximum dose of 40mg/kg/day on day 21, if tolerated, to achieve plasma level 50-100 mcg/mL.

Valproic Acid

Reduction of lymph node and/or spleen size measured by CT imaging, or physical exam and abdominal ultrasound. A clinical response is defined as a greater than 40% reduction in lymph node size and/or greater than 40% reduction in spleen size. A CT scan with contrast measured lymph node size as well as spleen size.

Number of Participants With Response

To Determine Whether the Treatment Alters, in Favorable Directions, Laboratory Markers of ALPS (e.g., Number of DNT Cells, Immunoglobin Levels, Vitamin B12 Levels, IL-10 Levels, Autoantibody Titers, Fas Mediated Apoptosis)

V. Koneti Rao, MD

ALPS

Hypersplenism

Lymphadenopathy

CT scans were done before and after treating the patient with valproic acid

CT Scan

Blood samples were collected before and after the intervention to monitor blood counts and biomarkers of ALPS

splenomegaly/نوبة

Biomarker for Gangliosidosis: BioGM1/BioGM2 (BioGM1/GM2)

Biomarker Validation for Niemann-Pick Disease, Type C: Safety and Efficacy of N-Acetyl Cysteine

Valproic Acid (Depakote[Registered Trademark]) to Treat Autoimmune Lymphoproliferative Syndrome (ALPS)

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