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

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.

Keywords

• lysosomal storage diseases
• consensus