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01.12.2014 | Research | Ausgabe 1/2014 Open Access

Orphanet Journal of Rare Diseases 1/2014

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

Zeitschrift:
Orphanet Journal of Rare Diseases > Ausgabe 1/2014
Autoren:
Christiane Kehrer, Samuel Groeschel, Birgit Kustermann-Kuhn, Friederike Bürger, Wolfgang Köhler, Alfried Kohlschütter, Annette Bley, Robert Steinfeld, Volkmar Gieselmann, Ingeborg Krägeloh-Mann
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1750-1172-9-18) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

CK made substantial contributions to conception and design of the study as well as to acquisition and interpretation of data and was involved in recruitment of patients. She studied the medical records, was responsible for standardised interviews by phone and drafted the paper. SG helped with the statistical analysis and interpretation of data and revised the manuscript critically for important intellectual content. BK and FB carried out biochemical analysis of measurement of Arylsulfatase A in leucocytes and sulfatides in urine and were substantially involved in recruitment of patients. WK was responsible for recruitment of patients with a juvenile form of MLD and acquisition and interpretation of data of natural course in juvenile MLD. AK was involved in the design of a standardised patients’ questionnaire. AB and RS were involved in recruitment of patients and acquisition of data. VG participated in the design of the study and the manuscript. IK-M was involved in conception and design of the study as well as in drafting the manuscript and gave final approval of the version to be published. All authors read and approved the final manuscript.

Abstract

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.
Zusatzmaterial
Authors’ original file for figure 1
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Authors’ original file for figure 5
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Literatur
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