Pompe s disease

Type II Pompe s disease Deficiency of lysosomal a-1 4- and 1 ->6-glucosldase (acid maltase) Fatal, accumulation of glycogen in lyso-somes, heart failure. 

Nadler, H. L. and Messina, A. M. "In-Utero Detection of Type-II Glycogenosis (Pompe s Disease). Lancet, (1969),... 

During product development, many of the initial non-clinical studies were undertaken in GAA knockout mice (i.e. mice devoid of a functional GAA gene), which serves as an animal model for Pompe s disease. The mice proved useful in assessing the pharmacodynamic effect of Myozyme on glycogen depletion and helped establish appropriate dosage regimens. The mice were also used to evaluate pharmacokinetics and biodistribution of GAA following its administration at clinically relevant doses. 

Gaucher s disease type I Fabry s disease Hurler s disease Pompe s disease Hurler s syndrome... 

Winkel, L. P., Van den Hout, J. M., Kamphoven, J. H. et al. Enzyme replacement therapy in late-onset Pompe s disease a three-year follow-up. Ann Neurol 55 495-502, 2004. 

Infantile, generalized cardiomegalic AMD, or Pompe s disease, usually becomes manifest in the first weeks or months of life, with failure to thrive, poor suck, generalized hypotonia and weakness, also termed floppy infant syndrome. Macroglossia is common, as is hepatomegaly, which, however, is rarely severe. There is massive cardio-megaly, with congestive heart failure. Weak respiratory muscles make these infants susceptible to pulmonary infection death usually occurs before the age of 1 year and invariably before the age of 2 years [6]. 

Serum CK is consistently increased in all forms of AMD. Forearm ischemic exercise causes a normal rise of venous lactate concentration in patients with childhood or adult AMD. The electrocardiogram (ECG) is altered in Pompe s disease, with a short P-R interval, giant QRS complexes and left ventricular or biventricular hypertrophy, but is usually normal in the later-onset forms. The EMG shows myopathic features and fibrillation potentials, bizarre high-frequency discharges and myotonic discharges. 

Muscle biopsy shows vacuolar myopathy of very severe degree affecting all fibers in Pompe s disease but of varying degree and distribution in childhood and adult AMD. In adult AMD, biopsy specimens from unaffected muscles may appear normal by light microscopy. The vacuoles contain PAS-positive material, a marker for glycogen. Electron microscopy shows abundant glycogen, both within membranous sacs, presumably lysosomes, and free in the cytoplasm. 

Lysosomal storage abnormalities, such as glycogenosis (Pompe s disease). Tay-Sachs, Krabbe s. Gaucher s, and Fabry s diseases, as well as melachromatic leukodystrophy, aspariylgiycosaminuria, and Niemann-Pick disease. Also included in this category are mucopolysaccharidoses. Hunter s, Scheie s, and Hurler s syndromes. 

II Acid maltase Pompe s disease Muscle weakness death by age 2 years (infantile variant)... 

Hers HG. Alpha-glucosidase deficiency in generalized glycogen-storage disease (Pompe s Disease). Biochem. J. 1963 86 11. 

Generalized glycogenosis typie II, also called Pompe s disease (J.C. PoMPE, 1932), is caused by a deficiency of lysosomal acidic al,4 glucosidase. This enzyme is responsible for the degradation of glycogen and maltose within the lysosomes. Glycogen is accumulated in all organs, particularly in the heart, but also in the liver. The disease may occur in the newborn (death due to heart failure, often within the first 12 months of life), but may also become manifest in infants and adults. Clinical symptoms include weakened skeletal... 

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