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.
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.
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.