Newborn screening for Krabbe disease is performed by direct measurement of GALC
enzymatic activity in dried blood spots either by tandem mass spectrometry (MS/MS) or by fluorometry (5).
L-a-Phosphatidylcholine (egg yolk) (PC), L-aPhosphatidylethanolamine (PE) and Galactocerebrosides (GalC
) (from bovine brain) were purchased from Sigma Chemicals Co.
Lysosomal enzyme testing showed galactocerebroside beta galactosidase or galactocerebrosidase (GALC
) level which was almost undetectable and definitely much below the 99th percentile for age and sex confirming the diagnosis of Krabbe disease.
The two cerebrosides most highly enriched on the surface of the oligodendrocyte cell body and throughout the myelin membrane, compared to other parts of the body, are the galactosylceramides, GalC
and sulphatide, which together make up 25-30% of human CNS lipids.
In our model, remyelination begins 10 to 14 days following intraspinal injection of antibodies to GalC
and remyelination of all axons is evident by 4 weeks .
Galactosylsphingosine (psychosine) is a neurotoxic sphingolipid degraded by GALC
. Predictably, affected individuals show progressive accumulation of psychosine in central and peripheral nerve tissue.
2012 will highlight how environmental sustainability has become a critical strategic planning issue as international trade and supply chains become more global.
The first disc was treated with 30 [micro]L of ASM cocktail, the second one with 30 [micro]L 5-plex cocktail containing S and IS for ABG, GAA, GLA, GALC
, and IDUA.
The New York State NBS laboratory has sequenced the coding regions of the galactosylceramidase (GALC
) gene in several hundred screen-positive samples out of about 2 million DBS tested for Krabbe disease.
Primers flanking exonic and promoter regions of the genes galactosylceramidase (GALC
),  medium and very long chain acyl-CoA dehydrogenases [acyl-CoA dehydrogenase, C-4 to C-12 straight chain (ACADM) and acyl-CoA dehydrogenase, very long chain ACADVL)], galactose-1-phosphate uridyl transferase (GALT), and phenylalanine hydroxylase (PAH) were designed in the NYS NBS program using the Primer3[TM] free software available at http://frodo.wi.mit.edu/primer3/.
Assays are described for acid sphingomyelinase (ASM) (Niemann-Pick-A/B disease), a-acid-glucosidase (GAA) (Pompe disease), [alpha]-galactosidase A (GLA) (Fabry disease), acid [beta]-glucocerebrosidase (ABG) (Gaucher disease), galactocerebrosidase (GALC
) (Krabbe disease), [alpha]-iduronidase (IDUA) (mucopolysaccharidosis I), iduronate-2-sulfatase (ID2S) (mucopolysaccharidosis II), N-acetyl-galactosamine-6-sulfatase (GAL6S) (mucopolysaccharidosis IVA), and N-acetyl-galactosamine-4-sulfatase (GAL4S) (mucopolysaccharidosis VI).
The expanded screening for LSDs included the analysis of acid [beta]-glucocerebrosidase (ABG), [alpha]-galactosidase (GLA), [alpha]-glucosidase (GAA), acid sphingomyelinase (ASM), galactocerebrosidase (GALC
), and iduronidase (IDUA) enzyme activities in the anonymized DBS samples.