A Natural History Study of Patients With GNE Myopathy and GNE-Related Diseases
A Natural History Study of Patients With GNE Myopathy and GNE-Related Diseases
Background:

 - GNE Myopathy is a disease that causes walking difficulties and increasing muscle weakness.
 It usually develops in young adults (between 20 and 30 years of age), and affects arm and leg
 muscles. HIBM is caused by mutations in a gene that may affect how the muscles function.
 Researchers want to learn more about the causes, symptoms, and effects of HIBM.

 Objectives:

 - To collect genetic and medical information from people with GNE Myopathy .

 Eligibility:

 - Individuals between 18 and 80 years of age who have GNE Myopathy and do not use a
 wheelchair. - Participants must be willing to stop any current treatment of HIBM while
 enrolled in the study.

 Design:

 -  Participants will be screened with a medical history, physical exam, and neurological
 exam.

 -  At the first visit, participants will have the following tests:

 -  Questionnaires about the impact of HIBM on daily activities, mood, and quality of life

 -  24-hour urine collection

 -  Blood samples

 -  Heart function tests

 -  Muscle strength and endurance tests, including walking

 -  Imaging study of the muscles

 -  Participants will return for followup visits at 6, 12, and 18 months. They may be asked
 to return for a final visit at 24 months. Not all tests will be performed at each visit.

 -  Treatment will not be provided as part of this protocol.

 For more information, visit our website: http://hibmstudy.nhgri.nih.gov/
This is a prospective observational study to evaluate patients with GNE myopathy and other
 GNE-related diseases. The GNE gene encodes for UDP-GlcNAc 2-epimerase/ManNAc kinase, the
 bifunctional enzyme that initiates and regulates intracellular sialic acid (Neu5Ac)
 biosynthesis and glycan sialylation. GNE myopathy is a rare, autosomal recessive myopathy
 with onset in early adulthood characterized by progressive skeletal muscle atrophy and
 weakness. The impairment of Neu5Ac production is presumed to cause decreased sialylation of
 muscle glycoproteins, resulting in muscle deterioration. Other GNE-related diseases such as
 congenital thrombocytopenia have been recently identified, but the pathophysiology is not
 well understood. In this protocol, we plan to evaluate patients with GNE myopathy and other
 GNE-related diseases clinically, biochemically, and molecularly to characterize the
 mechanisms of disease, to delineate the natural history, phenotypes, progression and
 complications of GNE-related diseases, and to identify endpoints and biomarkers to support
 clinical trials testing potential therapies.
-  INCLUSION CRITERIA:

 1. Age 4-80 years, either gender, inclusive.

 2. Diagnosis of GNE myopathy or GNE-related diseases based upon the identification
 of GNE gene mutations. Molecular confirmation of the diagnosis will be obtained
 for all subjects in the study.

 3. Subjects that are a carrier family member of a patient on the study are eligible
 to participate.

 4. Must be able to provide informed consent.

 EXCLUSION CRITERIA:

 1. Psychiatric illness or other diseases that would interfere with the subject s ability
 to comply with the requirements of this protocol.

 2. Hepatic laboratory parameters (aspartate aminotransferase [AST], alanine
 aminotransferase [ALT]) or renal laboratory parameters (creatinine, blood urea
 nitrogen [BUN]) greater than 3 times the upper limit of normal.

 3. Presence of clinically significant cardiovascular, pulmonary, hepatic, renal,
 hematological, metabolic, or gastrointestinal disease not related to the primary
 disease process.