Human ARSA (Arylsulfatase A) ELISA Kit

Metachromatic leukodystrophy (MLD) is a lethal neurodegenerative disease caused by a deficiency in the lysosomal arylsulfatase A (ARSA) enzyme leading to the accumulation of sulfatides in glial and neuronal cells. We previously demonstrated in ARSA-deficient mice that intracerebral injection of a serotype 5 adeno-associated vector (AAV) encoding human ARSA corrects the biochemical, neuropathological and behavioral abnormalities. However, before considering a potential clinical application, scaling-up issues should be addressed in large animals. Therefore, we performed intracerebral injection of the same AAV vector (total dose of 3.8 x 10(11) or 1.9 x 10(12) vector genome, three sites of injection in the right hemisphere, two deposits per site of injection) into three selected areas of the centrum semiovale white matter, or in the deep gray matter nuclei (caudate nucleus, putamen, thalamus) of six non-human primates to evaluate vector distribution, as well as expression and activity of human ARSA. The procedure was perfectly tolerated, without any adverse effect or change in neurobehavioral examination. AAV vector was detected in a brain volume of 12-15 cm(3) that corresponded to 37-46% of the injected hemisphere. ARSA enzyme was expressed in multiple interconnected brain areas over a distance of 22-33 mm. ARSA activity was increased by 12-38% in a brain volume that corresponded to 50-65% of injected hemisphere. These data provide substantial evidence for potential benefits of brain gene therapy in patients with MLD.

A cryptic duplication 22q13.31 to qter leads to a distinct phenotype with mental retardation, microcephaly and mild facial dysmorphism: We present a girl with a terminal 22q duplication due to all unbalanced chromosomal translocation: 46, XX, der(22)(qter -> q13.31 :: p11 -> qter). She presented with mild to moderate mental retardation. autism spectrum disorder, microcephaly and mild dysmorphic facial features. Because of nasal speech and mental retardation. FISH analysis for the DiGeorge/VCFS region was performed. In this analysis, an extra signal for the control probe LSI ARSA (22q13) on the short arm of one of the chromosomes 22 revealed the terminal duplication 22qter. The duplication was confirmed by means of IMb array-CGH and Further delineated as a 5.5 Mb region: 46, XX, dup(22)(q13.31qter)(CTA-268H5 -> CTB-99K24)x3. Important phenotypic variability has been described among patients with terminal 22q duplications. However, by considering the present patient and a careful selection of literature reports describing pure trisomy 22qter and comparably small duplicated regions 22q13.3 to qter, we find evidence tor a consistent clinical presentation: mild to moderate mental retardation, microcephaly and similar mild dysmorphic Features. Furthermore we conclude that small terminal duplications of chromosome 22q may be more common than generally assumed but may remain undetected by high resolution karyotyping. The application of array-CGH in patients with mental retardation and only very mild dysmorphism may allow to detect small 22qter duplications more frequently.