Metachromatic leukodystrophy
Metachromatic leukodystrophy is a demyelinating neurodegenerative disease characterized by an accumulation of characteristic lipids that form part of the myelin coating of nerve fibers called sulfatides. The pathology is due to a deficiency in the activity of the enzyme arylsulfatase A, which is responsible for degrading sulfatides.
The worldwide prevalence of metachromatic leukodystrophy is approximately 1 case per 40,000-160,000.
Symptoms
There are three forms of the disease: late infantile, juvenile and adult. The late infantile form is the most frequent and severe, usually beginning at the same age as learning to walk, with hypotonia, walking difficulties, optic atrophy and motor regression preceding mental deterioration.
The juvenile form begins around 4 or 5 years of age, with arrest of intellectual development, followed by motor regression, epileptic seizures and ataxia. The disease does not progress as rapidly as the infantile form, however, the prognosis remains very grave.
In the adult form, onset is around 15 years of age, although there is often no diagnosis until adulthood. Clinical signs are milder and include both motor and psychiatric disorders, with a slow progression.
Disease management
There is no specific treatment available for this disorder. Bone marrow transplantation or hematopoietic stem cell transplantation may be helpful in patients with the late infantile or juvenile form if applied before the onset of symptoms, in order to stabilize their neurocognitive functions. However, the therapeutic potential of this procedure remains debatable. Currently, the use of viral vectors and cellular gene therapy are being investigated, although these methods still require further research on their safety and efficacy.
Drug treatments such as warfarin, baclofen, simvastatin and prednisolone can be used to alleviate symptoms. Immunotherapy may also be used to prevent neuroinflammation. However, the efficacy of some drugs is still contradictory.
Genes analyzed
Bibliography
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Cesani, M., Lorioli, L., Grossi, S., et al . Mutation Update of ARSA and PSAP Genes Causing Metachromatic Leukodystrophy. Human mutation. 2016 Jan;37(1):16-27.
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Kurosawa, K., Ida, H., Eto, Y. Prevalence of arylsulphatase A mutations in 11 Japanese patients with metachromatic leukodystrophy: identification of two novel mutations. Journal of inherited metabolic disease. 1998 Oct;21(7):781-2.
Liaw, H. R., Lee, H. F., Chi, C. S., et al . Late infantile metachromatic leukodystrophy: Clinical manifestations of five Taiwanese patients and Genetic features in Asia. Orphanet journal of rare diseases. 2015 Nov 9;10:144.
Lissens, W., Vervoort, R., Van Regemorter, et al . A D255H substitution in the arylsulphatase A gene of two unrelated Belgian patients with late-infantile metachromatic leukodystrophy. Journal of inherited metabolic disease. 1996;19(6):782-6
Lugowska, A., Berger, J., Tylki-Szymañska, A., et al . High prevalence of I179S mutation in patients with late-onset metachromatic leukodystrophy. Clinical genetics. 2002 May;61(5):389-90.
Luzi, P., Rafi, M. A., Rao, H. Z., et al. Sixteen novel mutations in the arylsulfatase A gene causing metachromatic leukodystrophy. Gene. 2013 Nov 10;530(2):323-8.
