In the third, or adult, form there is a more benign truncal and proximal limb myopathy that is slowly progressive over many years and death is usually the result of weakness of respiratory muscles. At times, the only severe weakness is of the diaphragm, as in the case reported by Sivak and colleagues, making adult acid maltase deficiency part of a select group of neuromuscular disorders that may present in this way (along with motor neuron disease, nemaline myopathy, and myasthenia gravis). The liver and heart are not enlarged. CK values can be normal or slightly increased. The EMG discloses a number of abnormalities—brief motor unit potentials, fibrillation potentials, positive waves, bizarre high-frequency discharges, and occasional myotonic discharges (without clinical evidence of myotonia). The disease must be differentiated from other chronic adult myopathies, including polymyositis and the endocrine myopathies, and from motor neuron disease.
Aside from the elevation of the muscle-derived enzymes CK and of aldolase, blood studies are normal. A simply implemented dried blood spot screening test for alpha-glucosidase has been developed and, if it shows that there is no enzyme detectable, a biopsy can be omitted and the clinician can proceed to genetic testing. This screening test is particularly important in babies with suspected disease, as they are susceptible to general anesthesia that may be used to accomplish a biopsy.
The diagnosis of acid maltase deficiency in early-onset cases is readily confirmed by muscle biopsy, but later onset cases may show only nonspecific changes. The main features, when found, are vacuoles containing periodic acid-Schiff (PAS)–positive diastase-digestible material; they stain intensely for acid phosphatase. The glycogen particles lie in aggregates; electron microscopy shows some of them to occupy lysosomal vesicles and others, to lie free. The myofibrils are disrupted and some muscle fibers degenerate. Glycogen accumulation is more pronounced in type 1 fibers. The earlier mentioned blood-spot test is useful in cases, particularly those of late onset, that have the typical characteristics of disease but display only nonspecific histopathologic changes.
As indicated earlier, in the more severe infantile form of acid maltase deficiency, heart muscle and the large neurons of the spinal cord and brainstem may also accumulate glycogen and degenerate. The difference in severity between infant and adult forms relates to the completeness of enzyme deficiency, but possibly other factors are also at work as more than one of the three types may occur in the same family.
Treatment The adult who is threatened by respiratory failure should be observed frequently with measurements of vital capacity and blood gases. Umpleby and coworkers reported that a low-carbohydrate, high-protein diet may be beneficial. A few of our patients died unexpectedly during sleep. Respiratory support (rocking bed, nasal positive pressure, cough-assist devices, and negative-pressure cuirass) may prolong life.
Enzyme replacement therapy is available to treat Pompe disease. Recombinant acid alpha-glucosidase has been shown to prolong survival in the typical infantile Pompe case, but the benefits are modest in later-onset cases, although walking was improved and pulmonary function stabilized in one series (van der Ploeg et al). The agent is injected intravenously every 2 weeks. The same approach has been used in cases of infantile onset (Kishani et al).
Myophosphorylase Deficiency (Type V Glycogenosis; McArdle Disease, PYGM Mutation) and Phosphofructokinase Deficiency (Type VII Glycogenosis; Tarui Disease, PFKM Mutation)