An Observational Study to Assess Clinical Manifestations and Biomarkers in Amyotrophic Lateral Sclerosis Type 4 and Other Inherited Neurological Disorders of RNA Processing

Full Study Summary:

Objective:

To learn how the binding of RNA with DNA (R-loops) is related to neurological disease.

Eligibility:

People age 5 and older with ALS4, PEOB2, AGS, and AOA2. Healthy relatives and nonrelatives are also needed.

Design:

Participants may be screened with a review of x-rays and other medical records.

Healthy relative and nonrelative participants will have 1 visit. All other participants will have 4 visits over 3 years.

At visits, participants will undergo some or all of the following:

Medical history

Physical exam

Tests of muscle strength and volume and physical function

Blood tests

Pregnancy test (for some females)

Skin biopsy of forearm

Magnetic resonance imaging (MRI)

Dual x-ray absorptiometry (DEXA).

Some tests are optional.

The MRI uses a magnetic field and radio waves to take pictures. Participants will lie on a table that slides in and out of the scanner. The scanner makes noise. They will get earplugs.

The DEXA scan uses x-rays to take pictures.

MRI and DEXA will be used to measure muscle, fat, and lean body mass.

• Eligibility Criteria

  Gender:

  Female, Male

  Minimum Age:

  5

  Maximum Age:

  N/A

  Time since Symptom Onset:

  Time since Diagnosis:

  Can participants use Riluzole?

  
  

  INCLUSION CRITERIA

  ALS4 inclusion criteria:

  • Age 5 or above
  • Genetic diagnosis of ALS4 (heterozygous mutation in SETX)
  • Able to communicate well with the investigator, to understand and comply with the requirements of the study
  • Capacity to consent (adults) or assent (pediatric subjects) to the study

  Disease control inclusion criteria:

  • Age 5 or above
  • Genetic diagnosis of RNA processing defect mutation (RNaseH1, RNaseH2, recessive mutations in SETX)
  • Able to communicate well with the investigator, to understand and comply with the requirements of the study
  • Capacity to consent (adults) or assent (pediatric subjects) to the study

  Related, unaffected healthy control inclusion criteria:

  • Age 5 or above
  • Family history (first, second, or third degree relative) of RNA processing defect mutation (RNaseH1, RNaseH2, heterozygous or recessive mutations in SETX)
  • Able to communicate well with the investigator, to understand and comply with the requirements of the study
  • Capacity to consent (adults) or assent (pediatric subjects) to the study

  Unrelated, healthy control inclusion criteria:

  • Age 5 or above
  • Able to communicate well with the investigator, to understand and comply with the requirements of the study
  • Capacity to consent (adults) or assent (pediatric subjects) to the study

  EXCLUSION CRITERIA

  ALS4 exclusion criteria:

  • Patients with known claustrophobia, presence of pacemaker, ferromagnetic material in their body, or any other condition that would preclude MRI assessments

  Related, unaffected healthy control exclusion criteria:

  • Diagnosis of neuromuscular disease or weakness on physical examination
  • Pregnancy

  Unrelated, healthy control exclusion criteria:

  • Diagnosis of neuromuscular disease or weakness on physical examination
  • Patients with known claustrophobia, presence of pacemaker, ferromagnetic material in their body, or any other condition that would preclude MRI assessments

• Site Contact Information

  National Institutes of Health Clinical Center
  .(JavaScript must be enabled to view this email address) / 800-411-1222 ext TTY8664111010
  Bethesda, Maryland 20892
  United States