Excessive accumulation of lipids in tissues not designed for long term storage may underlie the clinical manifestations of weakened skeletal and cardiac muscle, fatty liver, pancreatitis, hypothyroidism, and type 2 diabetes. Diagnosis
Main physical signs include a fatty liver, a weakened and enlarged heart (cardiomyopathy), inflammation of the pancreas (pancreatitis), reduced thyroid activity (hypothyroidism), type 2 diabetes, abnormal levels of creatine kinase in blood, and increased weakness of proximal muscles due to fatty replacement of skeletal muscle fibers. Accurate diagnosis is complicated by symptomatic overlap with other disorders. One of the earliest symptoms to manifest clinically is peripheral limb weakness, which becomes progressively more severe over time. Specifically, asymmetric right shoulder weakness is an idiosyncratic hallmark of NLSD enabling it to be distinguished from myopathies arising from alternative muscular disorders. NLSD is often diagnosed by the presence of lipid inclusions within leukocytes (Jordan’ Anomaly), which can be detected using histochemical and electron microscopy. Image B shows the characteristic lipid accumulation in red blood cells, in a NLSD patient, as compared to a normal individual (Image A). Classically, NLSD is associated with myopathy and can, in some cases, be linked with icthyosis. Therefore, with these symptoms or diagnosis, it is likely that the patient could and would be diagnosed with NLSD. Although lipid accumulation is most prominent in  myocytes, hepatocytes, and granulocytes, other tissues displayed elevated deposits as well. For the purpose of diagnosis, MRIs have been used to identify large fat deposits within muscle tissue.
We select product candidates for diseases and conditions that represent a significant unmet medical need, have well-understood biology and provide an opportunity to be first-to-market or offer a significant benefit over existing products. Based on this business model, it is easy to understand why BioMarin would have targeted a disease like MPS I for treatment. It is, as described, an orphan condition with a well-defined mechanism. Furthermore, before the development of Aldurazyme, there were no drugs to treat MPS I, allowing BioMarin to be first-to-market with its new pharmaceutical. Since the release of Aldurazyme, one more drug has been released to treat MPS; Elaprase is a treatment for MPS II. In 2016, Aldurazyme had an average cost-per-patient of $355,816. Collaboration between BioMarin and Genzyme
BioMarin/Genzyme is a 50/50 Limited Liability Company which co-owns the intellectual rights to Aldurazyme and works collaboratively on research and development. BioMarin is responsible for the production of Aldurazyme. It sells the finished product to Genzyme, which is a fully owned subsidiary of Sanofi. Genzyme pays a 39.5% - 50% royalty quarterly on worldwide net product sales to BioMarin. A portion of this royalty is considered to be product transfer royalties, meaning that if any Aldurazyme goes unsold, BioMarin merely retains the product transfer royalty, while not receiving any further royalties. Only in the case of defective product  is Genzyme reimbursed for Aldurazyme product. References
Further reading
External links
"Mucopolysaccharidosis type I". MedlinePlus. NBK1162. "Laronidase". Drug Information Portal. U.S. National Library of Medicine. Iduronidase at the US National Library of Medicine Medical Subject Headings (MeSH)