The deficiency of this enzyme results in the accumulation of structurally normal glycogen in lysosomes and cytoplasm in affected individuals. Excessive glycogen storage within lysosomes may interrupt normal functioning of other organelles and lead to cellular injury. A putative homologue—acid alpha-glucosidase-related gene 1—has been identified in the nematode Caenorhabditis elegans. Diagnosis
In the early-onset form, an infant will present with poor feeding causing failure to thrive, or with difficulty breathing. The usual initial investigations include chest X ray, electrocardiogram and echocardiography. Typical findings are those of an enlarged heart with non specific conduction defects. Biochemical investigations include serum creatine kinase (typically increased 10 fold) with lesser elevations of the serum aldolase, aspartate transaminase, alanine transaminase and lactic dehydrogenase. Diagnosis is made by estimating the acid alpha glucosidase activity in either skin biopsy (fibroblasts), muscle biopsy (muscle cells) or in white blood cells. The choice of sample depends on the facilities available at the diagnostic laboratory.In the late-onset form, an adult will present with gradually progressive arm and leg weakness, with worsening respiratory function. Electromyography may be used initially to distinguish Pompe from other causes of limb weakness. The findings on biochemical tests are similar to those of the infantile form, with the caveat that the creatine kinase may be normal in some cases.
Several generic companies challenged the validity of the patents and filed Abbreviated New Drug Applications (ANDA) seeking market entry. Allergan responded by filing a lawsuit against the ANDA filers. In Allergan, Inc. v. Sandoz, Inc., the US Court of Appeals for the Federal Circuit ruled that Allergans composition-related patent claims were invalid based on obviousness, because brimonidine and timolol had already been marketed in the claimed concentrations. However, Allergans method claim (US Patent No. 7,030,149), which states "reducing the number of daily topical ophthalmic doses of brimonidine administered topically to an eye of a person in need thereof for the treatment of glaucoma or ocular hypertension from 3 to 2 times a day without loss of efficacy", was held to be non-obvious. As a result, generic companies are prevented from marketing generic versions of Combigan until its patent expiration in 2022.Combigan is supplied in 5 mL, 10 mL, and 15 mL bottles. In the United States, the cash price of one 5-mL eye dropper of Combigan ranges from $160 to $190. == References ==