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Clinical aspects of neuropathic lysosomal storage disorders

  • LSDs with Neurologic Involvement
  • Published:
Journal of Inherited Metabolic Disease

Abstract

The purpose of this review is to describe neurological phenotypes associated with lysosomal storage diseases (LSDs), focusing on features arising from primary neuronal involvement. Clinical presentation, progression and genetic data, are discussed in detail in Part 2, the electronic material. Main features are summarized in Part 1. Insights gained from several observational studies are discussed. Prospective studies of the natural history of most neuronopathic LSDs have been hampered by the rarity of these conditions and the short survival of affected patients. Increasingly, longitudinal observations relating to neurological manifestations are being reported. Better clinical studies are necessary, including repeated measurements of disease progression to facilitate the development of sensitive scoring systems and appropriate counseling of affected individuals and their families. Ideally, clinical studies should involve a large cohort. As treatment becomes available, knowledge of disease expression and factors that influence the phenotype may enable critical assessment of therapeutic outcomes. It is hoped that increased familiarity with the clinical expression of individual LSDs will allow early diagnosis, so families at risk are given options to consider during future pregnancies. Early diagnosis also permits the introduction of timely intervention, to favoring improved outcome in cases that are potentially treatable.

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Acknowledgements

We are indebted to the patients and their families who made this study possible. We also thank Dr. Roberto Giugliani and Dr. Leonardo Vedolin for MRI and patient pictures, and Dr. Gregory Pastores for critical reading of the manuscript. This work was supported by Brazilian funding agencies (CAPES, FAPERGS, FIPE-HCPA, CNPq). Prof. Jardim is supported by CNPq.

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None declared. As this is a review article, ethics approval was not required.

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Correspondence to Laura Bannach Jardim.

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Communicated by: Gregory Pastores

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Fig. E-1

A cherry-red spot in the macula (GM2 gangliosidosis, Tay-Sachs disease) (JPEG 1005 kb)

Fig. E-2

GM1 gangliosidosis patient showing a macroglossia, hypertelorism, epicanthus and coarse facial features; and b lumbar kyphosis due to dysplastic vertebrae (JPEG 48 kb)

Fig. E-3

Some magnetic resonance imaging (MRI) patterns found in patients with lysosomal storage disorders. a Hypointense thalami and diffuse white-matter (WM) abnormality in a patient with GM1 gangliosidosis. b WM abnormalities affecting the occipital, periventricular, and central WM and sparing U fibers in a patient with the juvenile form of metachromatic leukodystrophy (MLD). c Global atrophy and high signal intensity on occipital periventricular WM in an infantile patient with Krabbe disease. d Cerebral atrophy in a patient with infantile neuronal ceroid-lipofuscinosis (INCL) (JPEG 42 kb)

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Jardim, L.B., Villanueva, M.M., Souza, C.F.M. et al. Clinical aspects of neuropathic lysosomal storage disorders. J Inherit Metab Dis 33, 315–329 (2010). https://doi.org/10.1007/s10545-010-9079-5

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