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Krabbe disease in adults: phenotypic and genotypic update from a series of 11 cases and a review

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Journal of Inherited Metabolic Disease

Abstract

Krabbe disease usually presents as a severe leukodystrophy in early infancy and childhood. From a series of 11 patients and 30 cases previously reported in the literature we describe the clinical, radiological, electrophysiological and genetic features of adult Krabbe disease. Patients diagnosed after the age of 16 years were included in this study. They were further divided into three groups depending on age at symptoms onset: (1) childhood onset cases (n = 7); (2) adolescence onset cases (n = 6) and adult onset cases (n = 28). Overall, 96 % of patients in the adult-onset group presented with signs of pyramidal tracts dysfunction. Spastic paraparesis or tetraparesis became prominent in all cases. A peripheral neuropathy was present in 59 % of cases and was most often demyelinating (80 %). Other clinical signs encompassed dysarthria (31 %), cerebellar ataxia (27 %), pes cavus (27 %), deep sensory signs (23 %), tongue atrophy (15 %), optic neuropathy (12 %), cognitive decline (12 %). Cerebrospinal fluid protein concentration was moderately increased in 54 % of patients. Patients in the adolescent- and childhood-onset groups had similar presentations but were more likely to display optic neuropathy (33 % and 57 %) and cerebellar ataxia (50 % and 57 %). In the adult-onset group, the disease progressed slowly over more than 10 years, but a rapid course was observed in two patients. Abnormalities of brain MRI was similar in the three groups and included high signals of cortico-spinal tracts (94 % of cases), hyper-intensities of optic radiations (89 %) and hyper-intensities or atrophy of the posterior part of the corpus callosum (60 %). No clear genotype-phenotype relationship could be demonstrated.

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Authors and Affiliations

  1. Department of Neurology, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris and University Pierre&Marie Curie, Paris, France

    Rabab Debs, Caroline Papeix, Bertrand Degos, Bertrand Fontaine, Gérard Said & Frédéric Sedel

  2. Laboratoire des Maladies Héréditaires du Métabolisme et Laboratoire Gillet-Mérieux, Groupe Hospitalier Est, Hospices Civils de Lyon, 69500, Bron, France

    Roseline Froissart & Marie T. Vanier

  3. Department of Pediatric Neurology, CHU Kremlin Bicêtre, Assistance Publique–Hôpitaux de Paris, France and INSERM UMR745, University Paris-Descartes, Paris, France

    Patrick Aubourg

  4. Service d’endocrinologie et maladies métaboliques, Clinique endocrinologique Marc Linquette, CHU de Lille, France

    Claire Douillard

  5. Centre de Recherche de l’Institut du Cerveau et de la Moelle épinière, INSERM, UMR 546, Paris, France

    Bertrand Fontaine

  6. Department of Neurology, CHU de la Timone, Marseille, France

    Bertrand Audoin

  7. Service de Neurologie D et Centre de réference des maladies rares neuromusculaires, C.H.R.U Lille, Lille, France

    Arnaud Lacour

  8. INSERM, Unité 820, Faculté de Médecine Lyon Est, Université Lyon-1, Lyon, France

    Marie T. Vanier

  9. Neurometabolic unit, reference center for lysosomal diseases, GRC13-UPMC, Paris, France

    Frédéric Sedel

  10. Department of Neurology, Hôpital de la Salpêtrière, 47 Boulevard de l’Hôpital, 75651, Paris cedex 13, France

    Frédéric Sedel

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  1. Rabab Debs
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  2. Roseline Froissart
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  3. Patrick Aubourg
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  4. Caroline Papeix
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  5. Claire Douillard
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  6. Bertrand Degos
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  7. Bertrand Fontaine
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  8. Bertrand Audoin
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  9. Arnaud Lacour
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  10. Gérard Said
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  11. Marie T. Vanier
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  12. Frédéric Sedel
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Correspondence to Frédéric Sedel.

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Communicated by: Nicole Wolf

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Debs, R., Froissart, R., Aubourg, P. et al. Krabbe disease in adults: phenotypic and genotypic update from a series of 11 cases and a review. J Inherit Metab Dis 36, 859–868 (2013). https://doi.org/10.1007/s10545-012-9560-4

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  • DOI: https://doi.org/10.1007/s10545-012-9560-4

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