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<p>Neuronal ceroid lipofuscinoses (NCLs) are rare, inherited lysosomal storage disorders (LSDs) of the brain and retina. Gastrointestinal (GI) manifestations are reported in clinical practice but remain largely underexplored. Lysosomal dysfunction affects both the central and the peripheral nervous systems, including the enteric nervous system (ENS) where accumulation of storage material and neuronal loss may directly contribute to GI dysmotility. These insights, combined with emerging gene therapies targeting both brain and ENS pathology, underscore the need for validated GI endpoints in NCL research. We present a cross-sectional study assessing prevalence, progression, and clinical impact of GI symptoms in an Italian NCL cohort. Using caregiver-reported data and standardized tools — including the PedsQL™ GI Symptoms Scales and the Hamburg rating Scale — we evaluated GI burden and its correlation with neurological severity. Over 60% of caregivers reported GI disturbances, with constipation as the most prevalent and earliest onset symptom. Nutritional issues, such as dysphagia, were common but tended to appear later. GI symptoms correlated well with decline in quality of life, especially for Trouble Swallowing (<i>p</i><sub><i>adj</i></sub> <i>&lt;0.000001</i>), Food and Drink Limits (<i>p</i><sub><i>adj</i></sub> <i>&lt;0.000001</i>), and Constipation (<i>p</i><sub><i>adj</i></sub> <i>= 0.026006</i>). Problems with food and drink and swallowing problems correlated with the Hamburg rating Scale, while constipation did not, suggesting distinct underline mechanisms. Our findings support the importance of routine screening of GI symptoms in NCLs and their potential inclusion as extra-CNS endpoints in future therapeutic trials.</p>

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Gastrointestinal symptoms in neuronal ceroid lipofuscinoses (NCLs): an observational study on prevalence, timing of progression, and impact on quality of life

  • 期刊论文

  • 发表日期：

    2025年12月11日

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  • Stefania Della Vecchia,
  • Alessandro Simonati,
  • Maria Laura Manca,
  • Nicola Pietrafusa,
  • Marina Trivisano,
  • Costanza Calabrese,
  • Nicola Specchio,
  • Filippo Maria Santorelli

摘要

Neuronal ceroid lipofuscinoses (NCLs) are rare, inherited lysosomal storage disorders (LSDs) of the brain and retina. Gastrointestinal (GI) manifestations are reported in clinical practice but remain largely underexplored. Lysosomal dysfunction affects both the central and the peripheral nervous systems, including the enteric nervous system (ENS) where accumulation of storage material and neuronal loss may directly contribute to GI dysmotility. These insights, combined with emerging gene therapies targeting both brain and ENS pathology, underscore the need for validated GI endpoints in NCL research. We present a cross-sectional study assessing prevalence, progression, and clinical impact of GI symptoms in an Italian NCL cohort. Using caregiver-reported data and standardized tools — including the PedsQL™ GI Symptoms Scales and the Hamburg rating Scale — we evaluated GI burden and its correlation with neurological severity. Over 60% of caregivers reported GI disturbances, with constipation as the most prevalent and earliest onset symptom. Nutritional issues, such as dysphagia, were common but tended to appear later. GI symptoms correlated well with decline in quality of life, especially for Trouble Swallowing (padj <0.000001), Food and Drink Limits (padj <0.000001), and Constipation (padj = 0.026006). Problems with food and drink and swallowing problems correlated with the Hamburg rating Scale, while constipation did not, suggesting distinct underline mechanisms. Our findings support the importance of routine screening of GI symptoms in NCLs and their potential inclusion as extra-CNS endpoints in future therapeutic trials.