Diagnosis of glycogenosis type II

Abstract

The diagnosis of glycogenosis type II is often complicated by the rarity of the condition and the heterogeneity of the clinical manifestations of the disease. It is a progressive, debilitating, and often fatal neuromuscular disorder that manifests as a continuum of clinical phenotypes, which vary with respect to organ involvement, age at onset, and severity. Early diagnosis requires both increased awareness among physicians regarding the clinical characteristics of the disease and fast and reliable acid alpha-glucosidase (GAA) enzyme activity assays to confirm the GAA deficiency. The clinical diagnosis of glycogenosis type II is confirmed by virtual absence (found in infants) and marked reduced activity (found in juveniles and adults) of GAA enzyme in blood samples, cultured fibroblasts, and muscle biopsies. This article specifically highlights the need for early recognition of the clinical manifestation of the disease in infants, juveniles, and adults. Descriptions of the main clinical features of the condition, as well as differential diagnosis are included. In addition, the tests required for a confirmed diagnosis are described, and use of muscle imaging to evaluate muscle pathology is reviewed.

Hypertrophic Cardiomyopathy in Pompe Disease Is Not Limited to the Classic Infantile-Onset Phenotype

“…Slonim et al defined "nontypical" infantile-onset Pompe disease as those with less severe cardiomyopathy and longer survival of 1-2 years (Slonim et al 2000). Others have used "atypical infantile-onset Pompe disease" to characterize patients who have symptom onset before 1 year of age but with no cardiomyopathy (Bembi et al 2008;Kishnani et al 2012). Gungor and Reuser suggested using the term "childhood" Pompe disease to cover the gap between "classic infantile" and "adult" Pompe disease (Gungor and Reuser 2013).…”

Muscle biopsy in Pompe disease

“…Muscle biopsy may be requested in cases of suspected PD, but it is not routine. Typically, the histological diagnosis of childhood or adult PD is made during the investigation of Duchenne muscular dystrophy with a normal DNA analysis for dystrophin, limb girdle muscular dystrophy or adult-onset myopathies, as in our cases and previously reported by several authors 1,5,6 . In the past, most infantile cases already had a suspicion of PD because of the young age (months), hypotonia, heart disorder or respiratory insufficiency, but muscle biopsy was important to confirm the diagnosis.…”

“…Compared with other diseases, it is rarely observed in centers for neuromuscular disorders 2,3 . The clinical manifestation varies with age and the degree of enzyme deficiency, and three clinical forms are recognized: infantile or "classic", clinical manifestation present in the first months of life; childhood or "non-classic", clinical manifestation present after the first or second year of life; and adult or late onset, no clear cutoff between these forms 1 .…”

“…A molecular analysis can also be used to identify GAA mutations in highly suspected cases 5 . However, for the childhood and adult forms, the clinical symptoms, physical findings and laboratory features may indicate another muscle disorder, such as muscular dystrophy, or a metabolic muscle disorder 1,5,6 . In cases with no family history of PD, muscle biopsy is performed routinely in the diagnostic work-up.…”

Common recessive limb girdle muscular dystrophies differential diagnosis: why and how?

“…publication of this article, 27 LGMD subtypes have been classified, and at least five additional entities are candidates for classification (Table 1). From these 27 LGMD subtypes, 19 are autosomal recessive (more than 90% of the patients) and eight are autosomal dominant (less than 10% of the patients) ( Table 1). "-" not reported.…”