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Clinical history and new prognostic indicators in metachromatic leukodystrophy
Author(s) -
Del Carro U,
Biffi A,
Baldoli C,
Gerevini S,
Amadio S,
Fumagalli F,
Roncarolo MG,
Sessa M
Publication year - 2004
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/j.1085-9489.2004.009209ab.x
Subject(s) - metachromatic leukodystrophy , medicine , juvenile , natural history , age of onset , natural history study , white matter , polyneuropathy , leukodystrophy , pathology , arylsulfatase a , pediatrics , magnetic resonance imaging , biology , disease , radiology , genetics
Objective: To study clinical phenotypes and to increase knowledge of natural history of different variants of metachromatic leukodystrophy (MLD). Background: Little is known about factors influencing age of onset, progression rate and peripheral nerve involvement in MLD due to its rarity, heterogeneity and paucity of serial clinical and instrumental reports. Methods: 15 biochemically and molecularly characterized MLD patients were evaluated along a two‐year follow‐up period with clinical, electroneurographic (ENG) and brain MRI recordings. Results: Late infantile patients had a progressive and rapid course, whereas juvenile form showed marked variability. Different clinical presentations were associated with similar levels of ARSA activity; mutation screening indicated a high prevalence of rare or private mutations. In all late infantile and in the adult patient, ENG revealed a severe polyneuropathy. In juvenile patients a milder polyneuropathy or even normal tests were found. The earliest MRI change was periventricular white matter signal alterations, with initial involvement of posterior regions in a majority of late infantile patients, while in juvenile forms white matter lesions were mainly anterior. Conclusions: MLD course is highly variable and only partially influenced by age of onset, especially among juvenile patients. No clear‐cut correlations exist between clinical phenotype and biochemical or molecular characterization. The presence of peripheral neuropathy at onset seems a strong indicator of a poorer clinical outcome.