Common hereditary lysosomal storage diseases

A group of diverse inherited disorders that arise from deficiency of enzymes required for the breakdown of products of intermediary metabolism.

Diagnosis depends on a high index of suspicion, and is easily made by biochemical test or mutational analysis. Tissue biopsy is rarely required to make the diagnosis.

Many present in early childhood with hepatosplenomegaly, neurodevelopmental delay, cardiorespiratory disease, joint contractures, and failure to thrive. Others present later in childhood with pain, organ enlargement, skin rash, sensory organ damage, musculoskeletal abnormalities, muscle weakness, and neurodevelopmental delay.

Early referral to a specialist center is strongly advised so that patients and families may be assessed by a multidisciplinary team familiar with the disease.

Significant advances in treatment have occurred in recent years such that the outlook for patients has substantially changed. Specific treatments limited to certain subtypes include enzyme replacement therapy, substrate reduction therapy, and stem cell transplantation.

Lysosomal storage diseases (LSDs) are due to the inherited deficiency of one of over 40 lysosomal enzymes, and lead to accumulation of undegraded substrate in a range of organs and tissues.[1]Vellodi A. Lysosomal storage disorders. Br J Haematol. 2005 Feb;128(4):413-31. http://www.ncbi.nlm.nih.gov/pubmed/15686451?tool=bestpractice.com [2]Cox TM, Cachón-González MB. The cellular pathology of lysosomal diseases. J Pathol. 2012 Jan;226(2):241-54. http://www.ncbi.nlm.nih.gov/pubmed/21990005?tool=bestpractice.com They are multisystem and progressive disorders. Clinical manifestations are diverse; presentation may be in childhood or in adult life. New treatments, including replacement of the deficient enzyme, are changing the natural history of these diseases.[3]Brady R. Enzyme replacement therapy for lysosomal diseases. Annu Rev Med. 2006;57:283-96. http://www.ncbi.nlm.nih.gov/pubmed/16409150?tool=bestpractice.com [4]Mehta A, Winchester B, eds. Lysosomal storage disorders. A practical guide. Oxford: Wiley-Blackwell; 2012.