Clinical Studies of Progeria
Condition: Progeria
MeSH terms: Progeria
Study type: Observational

Summary: 
      This study will examine children with Hutchinson-Gilford Progeria syndrome, a genetic disease
      that causes many changes to the body over time, including heart disease, bone changes, hair
      loss, and joint and skin changes. Often called a "premature aging" disease, progeria does not
      mimic aging completely. This study will examine which body systems are affected in progeria
      and how each system is affected over time in order to try to develop new treatments.

      Patients with progeria who are between 6 months and 70 years of age and who are able to
      travel to the NIH in Bethesda, Md., may be eligible for this 5- to 10-year study.

      Participants come to the NIH Clinical Center for evaluation every 2 years. Each 4-5 day visit
      includes the following tests and procedures:

        -  Medical history and physical examination

        -  Blood tests to analyze cardiovascular risk factors, blood counts, blood chemistries, and
           for research

        -  Urine tests for sugar and proteins

        -  Photographs to study growth problems

        -  X-ray studies to determine bone density and body composition, such as body fat and
           muscle

        -  Electrocardiogram (EKG) and echocardiogram (heart ultrasound) to study the heart and
           blood vessels

        -  Lung function tests to measure energy consumption and lung capacity

        -  Skin biopsy (surgical removal of a small skin sample) to examine cellular changes

        -  Hearing tests

        -  Eye examination to evaluate eyesight, eye pressure and structures of the eye

        -  Physical therapy evaluation with stretching and exercises to measure how the joints bend
           and straighten

        -  Dental examination, including X-rays

        -  Meeting with a nutritionist who will track the patient's food intake and take body
           measurements

        -  Magnetic resonance imaging (MRI) for patients who are old enough to undergo the
           procedure without sedation. This test uses a magnetic field and radio waves to examine
           body organs. For this test, the patient must lie still in the scanner, a narrow
           cylindrical tube.

      Patients are provided the results of their medical tests. Information about the patient is
      submitted to the PRF Cell and Tissue Bank in Peabody, Massachusetts.
    

Detailed description: 
      Hutchison-Gilford Progeria Syndrome (HGPS) is a rare "premature aging" disease in which
      children die of severe atherosclerosis at an average age of thirteen years (range 8-20
      years). Children with HGPS appear healthy at birth, but within months display signs of growth
      failure, lipodystrophy, hair loss, and aged skin. Within just a few years they exhibit boney
      abnormalities including osteoporosis and resorption, coax valga and hip dislocation. The
      final height approximates 3 feet. Mortality is caused by generalized artherosclerosis leading
      to strokes and heart attacks. The gene defect causing HGPS has recently been identified as a
      single base mutation in the gene LMNA, coding for the nuclear protein Lamin A. The spectrum
      of effects of this gene defect on cellular function, and how these effects culminate in the
      HGPS disease phenotype, remain to be elucidated. Furthermore, no in-patient multisubject
      clinical evaluation of children with HGPS has ever been performed, and no therapy exists for
      any of the complications of HGPS. Hence, baseline studies are critical to determine the
      extent of organ involvement in HGPS, evaluate disease progression, and design clinical trials
      of potential treatments. The purpose of this study is to longitudinally investigate the
      disease characteristics of HGPS using state-of the-art measures of cardiovascular function,
      comprehensive laboratory testing, in vitro cell culture studies, and extensive medical
      consultations. HGPS patients will be admitted to the NIH Clinical center as inpatients for
      approximately 5 days every two years. The information emanating from the proposed studies
      will assist in assuring appropriate care for children with HGPS, provide a better
      understanding of the variations in phenotype of HGPS, and stimulate new research into HGPS
      and the aging diseases associated with HGPS, such as atherosclerosis. These studies will also
      allow us to evaluate new clinical outcome parameters and to design appropriate therapeutic
      interventions.
    

Observational model: Case-Only
Time perspective: Retrospective
Keywords: Ageing; Atherosclerosis; Lamin A; Lipodystrophy; Growth Impairment; Premature Aging; Hutchinson-Gilford Progeria Syndrome; HGPS