Lysosomal Storage Disorders: Marking Milestones and Moving Forward

Richard Moscicki, MD

The 12th International Congress of Human Genetics attracted approximately 7500 people this year, including scientists, clinicians, and industry representatives, a turnout that organizers said constituted the largest-ever gathering in the field. The American Society of Human Genetics hosted the congress in partnership with the International Federation of Human Genetics Societies. ICHG/ASHG 2011 was held at the Palais des Congrès de Montréal, Canada, October 11-15.

The mood of the congress often seemed buoyant as researchers discussed the doors that technology is helping to open in the study of inherited disorders.

“This is an extremely exciting time for human genetics,” said Evan Eichler, PhD, a professor of Genome Sciences at the University of Washington in Seattle, during a press briefing. “It is arguably one of the most transformative moments that we’re facing right now, with the ability to actually sequence the complete spectrum of genetic variation from common to rare, irrespective of class, type, and frequency, systematically across different genomes.”

Such enthusiasm was shared during discussions of lysosomal storage disorders (LSDs), a category of more than 40 rare metabolic conditions. Most LSDs are inherited conditions, such as Tay-Sachs disease, Gaucher disease, and Fabry disease.

LSDs occur when a particular enzyme or component in the lysosome organelle is deficient or malfunctions, causing the accumulation of undigested or partially digested macromolecules.^1-2 Nearly every bodily system can be affected, including a variety of hematologic functions.³

As a result, hematologists often treat patients with LSDs, particularly those with Gaucher disease, whose symptoms can include bone disease, chronic thrombocytopenia, and coagulation deficiencies.⁴ Initially, clinicians may suspect the patient has an oncologic condition such as leukemia or lymphoma.

Major changes have occurred in the past 20 years for patients with Gaucher disease, however, according to Richard Moscicki, MD, head of Clinical Development, Genzyme Corporation.

“It has been a real journey, not just for myself personally, but for the entire field. When we entered this area with the first enzyme replacement therapy, we didn’t know what to expect long term, and over this 20 years, since the first one was approved in 1991, we have seen that it has made a huge difference in patients’ lives.” Moscicki said that when he goes to a patient meeting today, as opposed to when he started 19 years ago with Genzyme, he no longer sees patients in wheelchairs.

Therapies for other conditions that are similar to Gaucher disease have since been developed, and despite the challenges of treating such complex conditions, researchers at the congress reported making strides in the understanding of LSDs, as well as in screening and treatment of patients.

References

1. Fong C. Lysosomal storage disorders. In The Merck Manual Online. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; 2010. Updated February 2010. Accessed November 18, 2011.
2. Kruer MC, Steiner RD. Lysosomal storage disease. In Kao A, ed. Medscape Reference. New York, NY: WebMD LLC; 2011. http://emedicine.medscape.com/article/1182830-overview. Updated June 28, 2011. Accessed November 18, 2011.
3. About lysosomal storage disorders: presentation and progression. Lysosomal Learning Website. http://www.lysosomallearning.com/healthcare/about/lsd_hc_abt_presentation.asp. Accessed November 18, 2011.
4. Making a diagnosis. Gaucher Care Website. http://www.gauchercare.com/en/healthcare/diagnosing/MakingADiagnosis.aspx#P56_2114. Accessed November 18, 2011.