Metachromatic leukodystrophy or MLD is an autosomal recessive hereditary disease, characterized by degeneration of myelin in the central and peripheral nervous system. The genetic defect causes the deficiency of the lysosomal enzyme Arisulfatasi A (ASA). Features of the MLD are the accumulation of sulphatide in the form of metachromatic granules and demyelination, which is more present in the segments of the nervous system characterized by a late myelination. The areas involved are distinguished by demyelination and accumulation of sulphatide in glial cells, Schwann cells, and other tissues (kidney , biliary tract, spleen, pancreas, adrenal gland …).
This disease has a frequency of 1 in 40,000 live births.
There are more clinical forms:
Congenital: onset at birth with crisis of apnea, cyanosis, seizures, hypotonia;
Late – Infantile: begins at1-2 years of age and has four-stage progressive course; first it arises with walking difficulties, ataxia, hypotonia, neuropathy, hyporeflexia, loss of acquired motor skills; then, after a few months evolvs with mental and speech regression, nystagmus, optic atrophy, muscle hypertonicity, in addition appears dystonia and spastic quadriplegia and decerebration; finally there is a complete inability to feed and death on average at 5 years from the onset;
Early-onset juvenile: starts at 4-6 years of age and is characterized by mental confusion, ataxia, sphincter incontinence, tremor, extrapyramidal signs, mental decline, polyneuropathy and optic atrophy; within a year the patient is no longer able to walk and finally, the disease progresses rapidly toward pseudobulbar palsy and spastic quadriplegia;
Juvenile late-onset: 6-12 years of age, it starts with behavioral, learning and walking disorders; the progression is slow, but in both juvenile forms life expectancy is at about 20 years of age;
Adult form: begins after the age of 16 with dementia, behavioral and personality disorders, memory loss, depression, neuropathy, pyramidal and extrapyramidal signs, ataxia, then appear nystagmus, optic atrophy, spastic quadriplegia, decortication; the progression of this form can be fast or slow;
Multiple sulfatase deficiency: it starts in the first year of age, is similar to the late – infantile form and shows typical signs of mucopolysaccharidosis (facial dysmorphisms, growth retardation, hepatosplenomegaly, skeletal abnormalities, ichthyosis);
Deficiency of SAP -1 (non-lysosomal activator protein): the protein is the heat-stable component of the cerebrosoide sulfate sulfatase enzyme and probably presents the substrate of the enzyme, the symptoms are similar to the juvenile form.
Services offered by the Institute for MLD
- SPECIALISTS ADVICES
- INFORMATION AND SUPPORT FOR PATIENTS AND THEIR RELATIVES
- GENETIC DIAGNOSIS
- BIOMOLECULAR AND CELLULAR RESEARCH
- NEUROPSYCHOMOTOR REHABILITATION
Galla Daniela, de Gemmis Paola, Anesi Laura, Berto Silvia, Dolcetta Diego, Hladnik Uros. An Italian Cohort Study Identifies Four New Pathologic Mutations in the ARSA Gene. J Mol Neurosci. 2013 Apr 5. [Epub ahead of print].
Bertelli M, Gallo S, Buda A,Cecchin S, Fabbri A, Lapucci C, Andrighetto G, Sidoti V, Lorusso L, Pandolfo M. Novel mutations in Arylsulfatase A gene in eight Italian families with metachromatic leukodystrophy. Journal of Clinical Neuroscience 2006 May; 13(4):443-8. IF 0,665 (2005)
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