Copyright © 2010 Frederick Furness Publishing 16 A focus on enzyme replacement therapies (ERT) for lysosomal storage diseases has led Shire Human Genetic Therapies, Inc (Shire HGT) to develop products for treating Fabry disease, Hunter syndrome, and type 1 Gaucher disease. These products are administered intravenously (IV) and are effective in treating the somatic symptoms of the disease. Devel...

Leukodystrophies are rare diseases caused by defects in the genes coding for lysosomal enzymes that degrade several glycosphingolipids. Gene therapy for leukodystrophies requires efficient distribution of the missing enzymes in CNS tissues to prevent demyelination and neurodegeneration. In this work, we targeted the external capsule (EC), a white matter region enriched in neuronal projections, ...

The following Table is meant to help neurologists and neuroradiologists in the diagnosis of a leukodystrophy or leukoencephalopathy suspected to be of genetic origin. We have tried to classify the large number of possible causes according to different criteria:-Basic pathogenetic mechanism (lysosomal, peroxisomal, or other molecular defects)-Recognizable neuroradiological criteria (hypomyelinat...

Metachromatic leukodystrophy and multiple sulfatase deficiency disorder are severe neurodegenerative diseases inherited as separate autosomal recessive traits. Arylsulfatase A (aryl-sulfate sulfohydrolase, EC 3.1.6.1) activity is deficient in both diseases but in multiple sulfatase deficiency disorder, activities of arylsulfatases B and C and other sulfatases are also reported to be reduced. So...

Pediatric Neurology Unit, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre RS, Brazil; Genetic Department, HCPA; Medical Genetic Service, HCPA; Professor of the Genetic Department, HCPA; Neuroradiology Department of Hospital Moinhos de Vento, Porto Alegre RS, Brazil; Pediatric Neurologist, Head of the Pediatric Neurology Unit, HCPA. Adjunct Professor, Universidade Federal do Rio Grande...

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal disorder caused by the deficiency of arylsulfatase A (ASA), resulting in impaired degradation of sulfatide, an essential sphingolipid of myelin. The clinical manifestations of MLD are characterized by progressive demyelination and subsequent neurological symptoms resulting in severe debilitation. The availability of therapeu...

Astrocytes are the predominant glial cell population in the central nervous system (CNS). Once considered only passive scaffolding elements, astrocytes are now recognised as cells playing essential roles in CNS development and function. They control extracellular water and ion homeostasis, provide substrates for energy metabolism, and regulate neurogenesis, myelination and synaptic transmission...

Oligodendrocytes are coupled by gap junctions (GJs) formed mainly by connexin47 (Cx47) and Cx32. Recessive GJC2/Cx47 mutations cause Pelizaeus-Merzbacher-like disease, a hypomyelinating leukodystrophy, while GJB1/Cx32 mutations cause neuropathy and chronic or acute-transient encephalopathy syndromes. Cx32/Cx47 double knockout (Cx32/Cx47dKO) mice develop severe CNS demyelination beginning at 1 m...

Metachromatic leukodystrophy (MLD) is a rare group of genetically-transmitted, autosomal-recessive, lipid-storage disorders characterised by accumulation of glycosphingolipids caused by deficiency of Arylsulfatase-A enzyme in lysosomes of cells necessary for formation of normal myelin sheath. The disease can present anytime from infancy to adulthood and is characterised by progressive deteriora...

BACKGROUND/AIMS Leukodystrophies due to abnormal production of myelin cause extensive morbidity in early life; their genetic background is still largely unknown. We aimed at reaching a molecular diagnosis in Ashkenazi-Jewish patients who suffered from developmental regression at 6-13 months, leukodystrophy and peripheral neuropathy. METHODS Exome analysis, determination of alkaline ceramidase...