Quand penser à une maladie de surcharge lysosomale (Morquio inclus) ?

Abstract

Lysosomal storage diseases (LSDs) are a group of over 70 diseases that are characterized by lysosomal dysfunction, caused by progressive accumulation of metabolites due to defects in lysosomal enzymes and degradation pathways, most of which are inherited as autosomal recessive traits. These disorders are individually rare but collectively affect more than 1 in 4000 live births. LSDs typically present in infancy and childhood, although adult- onset forms also occur. Lysosomal storage diseases (LSDs) are rare systemic and progressive genetic metabolic diseases, which present a wide heterogeneity (from severe to attenuated form) and a wide phenotypic spectrum of nonspecific manifestations, which may lead to considerable diagnostic delay. The precise diagnosis can be difficult or impossible, taking into account clinical variability and overlapping symptoms among LSD. The most of these disorders manifest with neurological, musculoskeletal and visceral signs. If severe subtypes are often readily diagnosed, the more attenuated subtypes are frequently missed or diagnosis is significantly delayed. Early diagnosis has become essential since effective disease-specific treatments, including enzyme replacement therapy and stem cell transplantation, have become available for certain LSDs, necessary to prevent the development of disabling and irreversible manifestations. Diagnosis of LSD is driven by clinical suspicion and several clinical approaches are possible: what presentations should prompt consideration of a LSD? Is it a neurological or a visceral phenotype? How thinking about a mucopolysaccharidoses, an oligosaccharidoses, a sphingolipidoses? How to discuss for each clinical sign or symptom the differential diagnosis of all LSD?