The diagnostic value of vacuolar characterization in muscular biopsy in Pompe's Disease

Introduction. Through muscle biopsy we can observe the formation of vacuoles that alter the structure of cells and tissues in Pompe's disease. The presence of these vacuoles varies as the disease progresses, relating to the broad clinical spectrum presented by the disease. Objectives. After confirming the disease, examine the possibility of diagnosing or excluding the diagnosis of Pompe's disease through the vacuolar characteristics presented. Method. Analysis of the muscle biopsy material of selected patients at the Neuromuscular Diseases Investigation Clinic at the Federal University of São Paulo. Through staining and histochemical techniques, a comparative study of the histological characteristics found was performed. Results. Thirty-three biopsies had the diagnosis of Pompe's disease confirmed, being 13 women and 20 men. Of this group, 23 received the diagnosis when they were 18 years old or more, and 10 received the diagnosis under the age of 18 years. Delimiting membrane and subsarcolemal location were the main vacuolar characteristic found, manifesting in 86.6% of the studied cases. Integration between the vacuole membranes was observed in 62.5% of the cases. We also found necrosis, replacement of muscle tissue by connective or adipose tissue, increased mitochondrial activity and absence of predominance in one type of fiber. Conclusion. Muscle biopsy allows to analyze a series of peculiarities presented by vacuoles in Pompe's Disease and, thus, it proves to be a sure technique, allowing to reach a quick conclusion and to identify determining factors for the clinical conduct and maintenance of quality of life of the patient with Pompe's disease.

Variable Genotype–Phenotype Correlation of Pompe's Disease Caused by a c.2015 G > A (p.Arg672Gln) Mutation in the GAA Gene

Pompe's disease occurs due to an autosomal recessive trait resulting from numerous distinctive mutations in the GAA gene. It manifests as a broad spectrum of clinical phenotypes with progressive weakness that impairs motor and respiratory functions being common for all its forms. Cardiac hypertrophy is a prominent feature of its classic infantile form. To date, the pathogenic variant c.2015G > A (p.Arg672Gln) in exon 14 of the GAA gene has been described in 10 children of different ethnic groups, with variable phenotypic presentations. This work describes three children from two unrelated families of Arab ethnicity who presented with infantile-onset Pompe's disease as a result of a c.2015G > A (p.Arg672Gln) mutation. The clinical course of the children we report was more severe than previous reports. This further emphasizes the lack of a strict genotype–phenotype correlation in regard to the unique c.2015G > A (p.R672Q) mutation that causes Pompe's disease. This information contributes to the knowledge of the phenotypic expression of the specific mutation c.2015G > A (p.Arg672Gln) that causes Pompe's disease.

Progressive thoracolumbar scoliosis culminating in the diagnosis of young pompe disease: case report

Introduction: Pompe’s disease is a neuromuscular condition caused by a metabolic disorder of autosomal recessive inheritance. The deficit of acid alpha-glucosidase causes accumulation of glycogen in the lysosomes of the striated and cardiac muscle. It presents in childhood: hypotonia and cardiorespiratory impairment; but at late-onset: axial and waist muscle weakness. Case report: Patient, female, 20 years old, non-consanguineous parents, with good intra-uterus fetal mobility, was born by cesarean delivery weighing 3.7 kilograms and 51 centimeters. She first walked without support and spoke her first words at 13 months of age. By the age of 12, she started progressive thoracolumbar scoliosis and underwent posterior spinal arthrodesis two years later. During the follow-up, muscle weakness was found. Furthermore, she presented macrocephaly, high myopia, fusion of cervical vertebrae, progressive scoliosis, dolichostenomelia and joint hypermobility. Extensive investigation was carried out with laboratory tests that showed CPK elevation, imaging tests and mutation research for facio-scapular-humeral muscular dystrophy and type 2A waistband muscular dystrophy. The incisional biopsy found mixed muscle changes with deposit of amorphous material. Pompe’s disease was confirmed by a significant reduction in alpha-glucosidase activity. The patient evolved with weakness in the legs and fatigue on moderate efforts, but also weakness in the lower limbs, detachable on the right and hyporeflexia, on physical examination. Conclusions: Progressive thoracolumbar scoliosis, refractory to postural and surgical corrections, should be an alert for differential diagnoses. Changes in axial musculature can be suggested and Pompe’s disease, a potentially treatable condition, must become relevant.

Rare Diseases in Neurology — Caring for a Patient with Pompe’s Disease

Introduction. Pompe disease, a severe metabolic myopathy, is caused by mutations in the gene coding for acid alphaglucosidase (GAA), what lead to intralysosomal accumulation of glycogen in all tissues, most notably in skeletal muscles. Pompe disease was the first documented lysosomal storage disease, nowadays we know around 60 similar disorders. Aim. Presentation of the clinical picture of a man with Pompe’s disease. Case Report. A man at the age of 40, diagnosis of the Pompe’s disease was made only at the age of 31. The first symptoms, indicating the patient’s development of the disease, were already present in the early school age. At first, the clinical picture presented by the patient led to the diagnosis of muscular dystrophy. Discussion. Pompe disease presents as a continuum of clinical phenotypes that differ by age of onset, severity, and organ involvement. Pompe disease affects people of all ages with varying degrees of severity. Two main broad types are recognized based on the onset of symptoms and the presence or absence of cardiomyopathy. Infantile onset Pompe disease (IOPD) as one, and the most severe for mod the disease. Other and less destructive is late-onset Pompe disease (LOPD) manifests any time after 12 months of age. The disease can be successfully treated by enzyme replacement therapy with alglucosidase alfa that was approved for human use in 2006. Conclusions. In big importance is nurses role as educators and support for the patients during their hospitalizations for medicine infusions twice a month. It time when the knowledge and significance of proper life style can be discussed and implemented to empower the patients. (JNNN 2019;8(4):170–176) Key Words: Pompe’s disease, treatment, diagnosis, care