Genetic and Family Studies of Inherited Muscle Diseases

The purposes of this study are to identify gene mutations in patients with the muscle diseases phosphofructokinase (PFK) deficiency, acid maltase deficiency (GAA deficiency) and to learn more about how these diseases develop. PFK deficiency is a mild, exercise-related illness. The childhood form of GAA deficiency (Pompe disease) affects the heart and liver and is rapidly fatal. The adult form begins in midlife and involves degeneration of skeletal muscles, leading to weakness and muscle wasting.

The following groups of individuals may be eligible for this study:

Group A: Patients with PFK deficiency, acid maltase deficiency, and relatives who also are affected. Participants in this group will undergo a brief medical and family history, blood sample collection, and possibly a physical examination, review of medical records, and interview with the patient's physician.

Group B: Unaffected family members of patients in group A, including both blood relatives and spouses. People in this group may be asked to provide a history and genetic information. A review of medical records, interview with the individual's physician, and blood sample may also be requested.

Group C: Control subjects. This group will provide a small blood sample or buccal mucosal sample (tissue sample collected by brushing the inside of the cheek). The samples will be coded and the investigators will not know the participants' identities. DNA from these samples will be analyzed for frequency of gene mutations.

Genetic counseling will be arranged for patients, as appropriate.

Study Overview

• Status: Completed
• Conditions: Myositis; Dermatomyositis; Polymyositis; Glycogen Storage Disease Type II; Glycogen Storage Disease Type VII

Detailed Description

This laboratory has defined several mutations in muscle diseases which mimic idiopathic inflammatory myopathy, (IIM, polymyositis or dermatomyositis), in particular, phosphofructokinase (PFK) deficiency (Type VII glycogenosis) and acid maltase (GAA) deficiency (Type II glycogenosis). Some patients with each of these autosomal recessive diseases have been shown to be genetic compounds, with different mutations on the alleles from each parent. In this protocol, we seek permission to receive and perform genetic screening on samples of tissue, blood, or DNA from patients with known metabolic muscle diseases, their family members, patients with undiagnosed muscle diseases, and groups of control subjects. Although we will know the names and histories of the patients, and may choose to admit them under other protocols for further studies, the tests we propose to perform on their DNA are currently only of laboratory interest and we believe that the outcome has no implications for the clinical care of the subjects. We propose to obtain oral consent, as appropriate to take a limited history and to speak to the patient's physician, from those patients and family members we speak to directly. All specimens obtained in family studies of a particular disease (e.g., PFK deficiency or GAA deficiency) will be obtained after written consent and will be tested only for the genes of the particular disease under study. After completion of those tests, the DNA, or products derived from it will be stored only under code so that it may be used as a control sample for other studies.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Patients known to have PFK deficiency, GAA deficiency or other known genetic muscle diseases and their clinically affected relatives.

Clinically unaffected family members of patients with PFK deficiency, GAA deficiency or other known genetic muscle diseases, including both blood relatives and spouses.

Control subjects. These will be individuals whose DNA has been gathered and coded by other investigators and provided to us solely for the purpose of population surveys of mutation frequency. Among such controls, may be unaffected individuals of the same racial or geographic origin as those with a particular mutation. If a convenient bank of such anonymous samples is unavailable, we will seek such individuals among those who work at the NIH or their families or friends.

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Publications and helpful links

General Publications

• Plotz PH, Dalakas M, Leff RL, Love LA, Miller FW, Cronin ME. Current concepts in the idiopathic inflammatory myopathies: polymyositis, dermatomyositis, and related disorders. Ann Intern Med. 1989 Jul 15;111(2):143-57. doi: 10.7326/0003-4819-111-2-143.
• Plotz PH. Not myositis. A series of chance encounters. JAMA. 1992 Oct 21;268(15):2074-7. doi: 10.1001/jama.268.15.2074. No abstract available.
• Raben N, Sherman J, Miller F, Mena H, Plotz P. A 5' splice junction mutation leading to exon deletion in an Ashkenazic Jewish family with phosphofructokinase deficiency (Tarui disease). J Biol Chem. 1993 Mar 5;268(7):4963-7.

Study record dates

Study Major Dates

• Study Start: May 1, 1993
• Study Completion: March 1, 2002

Study Registration Dates

• First Submitted: November 3, 1999
• First Submitted That Met QC Criteria: November 3, 1999
• First Posted (Estimate): November 4, 1999

Study Record Updates

• Last Update Posted (Estimate): March 5, 2008
• Last Update Submitted That Met QC Criteria: March 4, 2008
• Last Verified: March 1, 2002

More Information

Terms related to this study

• Keywords: Myopathy; Pompe; Phosphofructokinase; Acid Maltase; Muscle Diseases; Genetic Muscle Diseases
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Connective Tissue Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Lysosomal Storage Diseases, Nervous System; Muscular Dystrophies; Disease; Muscular Diseases; Myositis; Dermatomyositis; Metabolic Diseases; Polymyositis; Glycogen Storage Disease Type II; Glycogen Storage Disease; Glycogen Storage Disease Type VII
• Other Study ID Numbers: 930143; 93-AR-0143