Disruptions in speech, language and social communication in lysosomal storage diseases

Communication enables social connection, autonomy and identity, making it a fundamental domain of human functioning. In lysosomal storage diseases (LSDs), progressive neurological dysfunction can severely disrupt speech, language and social communication, resulting in profound isolation and reduced quality of life. LSDs are a heterogeneous group of more than 70 inherited metabolic disorders caused by lysosomal dysfunction and substrate accumulation, leading to severe neurological consequences and multisystem pathology. LSDs are classified according to the biochemical nature of the accumulating substrate, reflecting both the underlying enzymatic defect and clinical phenotype. Disease groups include sphingolipidoses (e.g., Gaucher disease), mucopolysaccharidoses (e.g., Hurler syndrome [MPS I]), glycoproteinoses (e.g., aspartylglycosaminuria), gangliosidoses (e.g., Tay-Sachs disease), neuronal ceroid lipofuscinoses (e.g., Batten Disease [CLN3]) and other lipid storage disorders such as Pompe disease or Niemann Pick Type C. Clinical presentations are highly variable, with neurodevelopmental symptoms presenting in infancy or early childhood for many. In this review, we synthesize evidence on speech, language, and social communication phenotypes across lysosomal storage diseases, examining how they can mirror underlying neurodegenerative processes and provide insight into disease progression and neurological vulnerability. We discuss the potential of communication phenotyping to improve diagnosis and prognostic stratification, inform therapeutic monitoring, and guide timely, targeted interventions to preserve social connection and quality of life.