Consensus position statement for the diagnosis and treatment of lysosomal storage diseases with neurological manifestations

2023

Abstract

Lysosomal storage diseases involve about 50 rare genetic metabolic diseases engaging  various mutations/pathological variants that cause enzyme deficiency and lysosomal  dysfunction due to accumulation of certain substrates in them: lipids, glycoproteins, and  mucopolysaccharides. These diseases induce multiple organ involvement and have a  progressive course. They are mainly inherited in an autosomal recessive (AR) manner, e.g.  Niemann-Pick disease type C, and, in rare cases, in an X-recessive (XR) (Fabry disease and  Hunter disease (MPS II)) or an autosomal dominant (AD) manner (neuronal ceroid  lipofuscinosis type 4 (NCL4)). Disease incidence is about 1/7,700 births. Disease prevalence  is about 1:100,000 but occasionally reaches 1:5,000–1:10,000. The onset is usually in  childhood and infantile, late infantile, pediatric, adolescent, and adult disease forms have been  characterized. Clinical syndromes in the presence of neurological manifestations depend on  the site of substrate accumulation and most often impair the central nervous system as well as,  less commonly, the peripheral nervous system, sometimes—the muscles, while multiple organ  involvement (heart, vessels, kidneys, liver, spleen, etc.) is also possible.