Language and cognition in children with metachromatic leukodystrophy: onset and natural course in a nationwide cohort

Orphanet Journal of Rare Diseases

Ingeborg Krägeloh-Mann¹  Volkmar Gieselmann⁶  Robert Steinfeld⁵  Annette Bley²  Alfried Kohlschütter²  Wolfgang Köhler⁴  Friederike Bürger³  Birgit Kustermann-Kuhn¹  Samuel Groeschel¹  Christiane Kehrer¹ 

[1] Department of Paediatric Neurology and Developmental Medicine, University Children’s Hospital, Hoppe-Seyler-Strasse 1, 72076 Tübingen, Germany;Department of Paediatrics, University Children’s Hospital Hamburg Eppendorf, Martinistr. 52, Hamburg 20246, Germany;University Children’s Hospital, Metabolic Centre Heidelberg, Metabolic Laboratory, Im Neuenheimer Feld 430, Heidelberg 69120, Germany;Fachkrankenhaus Hubertusburg, Hubertusburg, Wermsdorf 04779, Germany;Department of Child and Adolescent Health, Division of Neuropediatrics, University Medical Center Göttingen, Robert-Koch-Str. 40, Göttingen 37075, Germany;Department of Physiology, University of Bonn, Nussallee 11, Bonn 53115, Germany

关键词: Reference data;    Decline of language and cognition;    Onset and first symptoms;    Natural course;    Metachromatic leukodystrophy;   

Others  :  863259
DOI  :  10.1186/1750-1172-9-18

 received in 2013-11-05, accepted in 2014-01-10,  发布年份 2014

【 摘 要 】

Background

Metachromatic leukodystrophy (MLD) is a rare, genetic neurodegenerative disease. It leads to progressive demyelination resulting in regression of development and early death. With regard to experimental therapies, knowledge of the natural course of the disease is highly important. We aimed to analyse onset and character of first symptoms in MLD and to provide detailed natural course data concerning language and cognition.

Methods

Patients with MLD were recruited nationwide within the scope of the German research network LEUKONET. 59 patients’ questionnaires (23 late-infantile, 36 juvenile) were analysed.

Results

Time from first symptoms (at a median age of 1.5 years in late-infantile and 6 years in juvenile MLD) to diagnosis took one year in late-infantile and two years in juvenile patients on average. Gait disturbances and abnormal movement patterns were first signs in all patients with late-infantile and in most with juvenile MLD. Onset in the latter was additionally characterized by problems in concentration, behaviour and fine motor function (p = 0.0011, p < 0.0001, and p = 0.0012). Half of late-infantile patients did not learn to speak in complete sentences after an initially normal language acquisition. They showed a rapid language decline with first language difficulties at a median age of 2.5 years and complete loss of expressive language within several months (median age 32, range 22–47 months). This was followed by total loss of communication at a median age of around four years. In juvenile patients, language decline was more protracted, and problems in concentration and behaviour were followed by decline in skills for reading, writing and calculating around four years after disease onset.

Conclusions

Our data reflect the natural course of decline in language and cognition in late-infantile and juvenile MLD in a large cohort over a long observation period. This is especially relevant to juvenile patients where the disease course is protracted and prospective studies are hardly feasible. Knowledge of first symptoms may lead to earlier diagnosis and subsequently to a better outcome following therapeutic intervention. Our data may serve as a reference for individual treatment decisions and for evaluation of clinical outcome after treatment intervention.

【 授权许可】

   
2014 Kehrer et al.; licensee BioMed Central Ltd.

【 图 表 】

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