Treatable lysosomal storage diseases in the advent of disease‐specific therapy

Abstract

Lysosomal storage diseases (LSD) comprise a rare and heterogeneous group of nearly 50 heritable metabolic disorders caused by mutations in proteins critical for cellular lysosomal function. Defects in the activity of these proteins in multiple organs leads to progressive intra‐lysosomal accumulation of specific substrates, resulting in disruption of cellular functions, extracellular inflammatory responses, tissue damage and organ dysfunction. The classification and clinical presentation of different LSD are dependent on the type of accumulated substrate. Some clinical signs and symptoms are common across multiple LSD, while others are more specific to a particular syndrome. Due to the rarity and wide clinical diversity of LSD, identification and diagnosis can be challenging, and in many cases diagnosis is delayed for months or years. Treatments, such as enzyme replacement therapy, haemopoietic stem cell transplantation and substrate reduction therapy, are now available for some of the LSD. For maximum effect, therapy must be initiated prior to the occurrence of irreversible tissue damage, highlighting the importance of prompt diagnosis. Herein, we discuss the clinical presentation, diagnosis and treatment of four of the treatable LSD: Gaucher disease, Fabry disease, Pompe disease, and two of the mucopolysaccharidoses (I and II). For each disease, we present illustrative case studies to help increase awareness of their clinical presentation and possible treatment outcomes.

The Journal in 2020

“…I recognise that many among you still would prefer a print copy (the April 2020 issue was the last print issue) to hold and read in all sorts of locations, so if this change has caused you disquiet, please make your views known to us here or directly to the College office. There was a Supplement print issue in December 2020 that you would have received if you are a subscriber on Treatable Lysosomal Storage Diseases 2 . A final (online) supplement was on HIV Infection in Australia 3 …”

Ferroptosis and Its Modulation by Autophagy in Light of the Pathogenesis of Lysosomal Storage Diseases

“…However, this therapy is inefficient in treatment of the central nervous system, since intravenously administered enzyme cannot efficiently cross the blood–brain barrier. Finally, gene therapy is a promising option, and there are many studies ongoing which are focused on the use of this procedure in LSD; however, to date, no gene therapy for this group of diseases has been registered [ 8 , 9 , 10 ].…”

Gene Therapy for Mucopolysaccharidosis Type II—A Review of the Current Possibilities

“…Mucopolysaccharidosis type II (MPS II, OMIM #309900), also called Hunter syndrome, is a rare monogenic disease belonging to the group of lysosomal storage disorders (LSDs). The estimated incidence of MPS II is 0.3–0.7/100,000 births [ 1 ]. The condition occurs more often in the countries of East Asia than in Europe [ 2 ].…”

“…The discovery of this phenomenon contributed to the acceleration of studies on therapeutic agents. Currently, the mainstay of treatment is enzyme replacement therapy (ERT) using human recombinant iduronate 2-sulphatase administered intravenously [ 1 ]. Thanks to ERT, it is possible to reduce the concentration of GAGs in the urine, reduce the size of the liver and spleen, and improve physical tolerance and stabilize the bone and cardiac abnormalities.…”