Natural History Study of Patients With Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency

Summary

Succinic Semialdehyde Dehydrogenase deficiency (SSADHD) is a rare autosomal recessive disease that interferes with the catabolism of the major inhibitory neurotransmitter gamma-amino butyric acid (GABA) and furthermore leads to accumulation of various potential toxic metabolites, most prominently gamma hydroxybutyric acid (GHB). Current research indicates that there is developmental delay and significant neurophysiological and biochemical alterations in SSADHD patients, but whether disease presentation varies with age is not known. The investigators propose to determine the natural course of the clinical presentation of SSADHD; to determine the natural course of neurophysiological and biochemical indices known to be altered in SSADHD; and to identify neurophysiological and biochemical predictors of clinical severity.

The overall objective is to define the natural course of the clinical, neurophysiological and biochemical spectrum of SSADHD. Secondary objectives include the identification of biomarkers that correlate with disease phenotype and predict clinical outcomes, and the creation of an international SSADHD data repository for future investigation of pathogenesis and therapy.

Conditions

• Succinic Semialdehyde Dehydrogenase Deficiency

Interventions

DEVICE

Transcranial magnetic stimulation (TMS)

Transcranial magnetic stimulation (TMS) is a method for noninvasive electrical cortical stimulation, where small intracranial currents are generated by a powerful, fluctuating, extracranial magnetic field. TMS is unique in its capacity for experimental, diagnostic, and therapeutic utility. Single pulse (spTMS) and paired-pulse TMS (ppTMS) have been used extensively to study, measure, and modulate cortical excitability and plasticity.

DEVICE

Magnetic resonance imaging (MRI)

These will be outpatient MRI studies that are planned without sedation. Subjects enrolled at BCH will undergo brain MRI, including volumetric MRI, MRS, and diffusion tensor imaging (DTI). The data will help define the natural history of brain volume, brain myelination and spectroscopic (e.g. GABA) abnormalities.

DEVICE

Electroencephalogram (EEG)

These will be outpatient EEG recordings that span 20-60 minutes and done without sedation. Recordings will be performed using electrode locations specified by the international 10-20 system for standard clinical practice.

PROCEDURE

Bio-specimen Collection

Bio-specimen collection will include blood, urine, saliva, hair, stool, and a skin biopsy. Blood, urine, saliva, blood spots, and hair samples will also be banked for to-be-determined (TBD) studies.

Sponsors & Collaborators

• Washington State University

  collaborator OTHER

• University of South Florida

  collaborator OTHER

• University Hospital Heidelberg

  collaborator OTHER

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

  collaborator NIH

• Boston Children's Hospital

  lead OTHER

Principal Investigators

• Phillip L Pearl, MD · Boston Children's Hospital/Harvard Medical School

• K. Michael Gibson, PhD · Washington State University

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-01-15

Primary Completion

2029-05-31

Completion

2029-06-30

Countries

• United States
• Germany
• Spain
• United Kingdom

Study Locations