Newborn screening for lysosomal storage disorders

Abstract

Lysosomes are intracellular organelles containing acid hydrolases that degrade biological macromolecules. Lysosomal storage disorders (LSDs) are caused by absent activity of one or more of these enzymes due to mutations of genes encoding lysosomal hydrolases or enzymes that process, target, and transport these enzymes. The specific signs and symptoms of each LSD derive from the type of material accumulated within the lysosome, the site (organ) of accumulation and the response of the body (sometimes in the form of an inflammatory or immune response) to the accumulated material. Interest for inclusion of these disorders in newborn screening programs derives from the availability of effective therapy in the form of enzyme replacement or substrate reduction therapy and bone marrow transplant that may improve long-term outcome especially if started prior to irreversible organ damage. Based on the availability of therapy and suitable screening methods, Gaucher disease, Fabry disease, Pompe disease, mucopolysaccharidosis I and II, Niemann-Pick disease, and Krabbe disease are candidates for newborn screening. Pilot newborn screening projects have been performed for some of these conditions that indicate the feasibility of this approach. This review will provide insight into these screening strategies and discuss their advantages and limitations. © 2011 Wiley-Liss, Inc.

Enzyme Replacement Therapy in Mucopolysaccharidosis II Patients Under 1 Year of Age

“…This is in part because identifying and diagnosing very young patients without a family history of the disease generally requires newborn screening, which has not yet been generally instituted for MPS II (Nakamura et al 2011). In the HOS study of patients under 6 years of age, ERT effectiveness as assayed by reductions in liver size and uGAG levels was found to be similar between both the younger and older groups of patients, but the clinical significance in altering the longterm disease course could not be evaluated using the available registry data (Muenzer et al 2011a).…”

“…Long-term follow-up of these and other MPS II patients who began therapy within the first months of life will provide valuable information on the ability of ERT to possibly prevent or delay the development of certain disease manifestations. Such efforts would be greatly helped by the implementation of newborn screening programs for this disorder (Nakamura et al 2011). …”

Emerging uses for pediatric hematopoietic stem cells

“…Another area in which HCT can be curative is certain inherited metabolic and genetic disorders, such as Hurler syndrome, osteopetrosis, Gaucher disease, and others (15)(16)(17)(18)(19). Many of these are lysosomal or peroxisomal storage disorders.…”

“…Although this can be very useful in the milder syndromes, enzyme replacement therapy is limited by the inability of the externally provided enzymes to cross the blood-brain barrier, and as such does not work for diseases with central nervous system involvement. As single gene disorders, these are obvious candidates for gene therapy (15,20). However, the only current treatment option that can treat disorders with central nervous system involvement is HCT in the form of bone marrow or cord blood transplantation (16)(17)(18).…”

“…Although the majority of trials have been aimed at cancer, other diseases such as primary immunodeficiencies have been studied as well (34). Additional diseases, like autoimmune diseases (35) and inherited metabolic disorders (15) are also in principle open to this treatment option, although with various limitations. One limitation for severe inherited metabolic diseases is the fact that the time to effective treatment needs to be as short as possible (17,18).…”