Though storage disorders are rare, collectively the incidence is 1:6000 in Western countries while in India this may be higher due to ethnical variation.
Our study of nearly 600 children with developmental regression, hepatosplenomegaly, neuroregression and skeletal dysplasia shows that 33% of such children may have storage disorder. It is likely that every year almost 6000 to 8000 children are born with storage disorders in India, most of which remain undiagnosed due to lack of awareness, limited option for treatment and facility of diagnosis. Although with recent availability of enzyme replacement therapy for disorders like MPS, Fabry, Gaucher, NPD and Pompe there is a growing interest among clinicians to diagnose these cases at an early age.
At FRIGE – IHG, we have the facility to test large number of lysosomal enzymes which are specific for various lysosomal storage disorders.
Children with dysmorphic features, failure to thrive, regression of learned skills, corneal clouding, hepatosplenomegaly, cherry red spot, hearing loss, neuroregression, skeletal dysplasia, respiratory distress with muscular myopathy, and cardiomegaly are at the high risk of storage disorder and need further study of enzymes.
There is no common screening test except plasma chitotriosidase which is markedly elevated in children with Gaucher disease and Niemann Pick A/B type diseases, qualitative and quantitative analysis for GAG from urine for MPS and I cell screen from plasma for I-cell disease. However final confirmation is needed by lysosomal enzyme study either from leucocytes, plasma or fibroblasts.
| SCREENIG FOR VARIOUS LSD’s |
| I-Cell Screening |
Mucolipidosis II |
| Plasma Chitotriosidase |
Gaucher & NPD A/B Screening |
| MPS Screening |
|
| Azure A Spot test |
MPS I – VII |
| GAG Quantitative analysis |
MPS I – VII |
| GAG Qualitative analysis |
MPS I – VII |
(MPS electrophoresis) |
|
| |
| ENZYMES |
DISORDER |
Mucopolysaccharidosis |
| Alpha- Iduronidase |
Hurler Syndrome, MPS I |
| Alpha- Iduronate Sulphate |
Hunter Syndrome- MPS II |
| Heparan N-sulfatase |
Sanfilippo Syndrome, MPS IIIA |
| Plasma N- Acetyl- A- D- Glucosaminidase |
Sanfilippo Syndrome, MPS IIIB |
| Beta-Galactosidase-6-Sulphate-Sulphatase |
Morquio Syndrome, MPS IVA |
| Beta - Galactosidase |
Morquio Syndrome, MPS IVB |
| Arylsulfatase B |
Maroteaux-Lamy Syndrome, MPS VI |
| Beta- Glucuronidase |
Sly Syndrome, MPS VII |
| |
Glycoproteins degradation |
| Alpha- Fucosidase |
Fucosidosis |
| Alpha- Mannosidase |
Mannosidosis |
| |
Glycolipids and lipids |
| Beta - Galactosidase |
GM1 Gangliosidosis |
| Hexosaminidase (Total) |
GM2 Gangliosidosis |
| Hexosaminidase (A) |
GM2 Gangliosidosis |
| Sphingomyelinase |
Niemann Pick Disease A & B |
| Beta - Glucosidase |
Gaucher's Disease |
| |
Sulphatides |
| Arylsulfatase A |
Metachromatic Leucodystrophy, MLD |
| Beta-Galactocerebrosidase |
Krabbe Disease |
| |
| Glycogen Storage |
| Alpha - 1,4 Glucosidase |
Pompe Disease, GSD II |
| (With/without acarbose) |
|
| |
| Globotriaosylceramide |
| Alpha - Galactosidase |
Fabry's Disease |
| |
Defects in protein degradation |
| Tripeptidyl Peptidase |
Late infantile Ceroid lipofuscinosis II |
| Palmitoyl-protein thioesterase |
Infantile Ceroid lipofuscinosis I |
| |
Defects in degradation of triglycerides and cholesteryls ester |
| Acid lipase |
Wolman disease |
| |
Defects in lysosomal transporters |
| Sialic Acid |
Sialic Acid Storage Disorder |
| |
Defects in lysosomal trafficking proteins |
| NPC1 |
Niemann Pick type C |
FRIGE also offers different panel study for LSD’s. |
| |
Enzymes in the NEURODEGENERATIVE (and other) screens which can be assayed initially on plasma: |
| |
| Enzyme:Disorder: |
| Arylsulphatase A |
I-cell |
| alpha-fucosidase |
Fucosidosis |
| beta-glucuronidase |
MPS VII |
| Total beta-hexosaminidase |
Sandhoff |
| beta-hexosaminidase A |
Tay Sachs/ B1 variant |
| alpha-mannosidase |
alpha-mannosidosis |
| Chitotriosidase |
Gaucher disease |
| |
also helpful indicator of other LSD |
Enzymes in the NEURODEGENERATIVE (and other) screens which can be assayed initially on leucocytes |
| |
| Enzyme |
Disorder |
| Arylsulphatase A |
Metachromatic leucodystrophy |
| Galactocerebrosidase |
Krabbe leucodystrophy |
| Beta-galactosidase |
GM1 Gangliosidosis |
| Palmitoyl protein thioesterase |
Infantile (INCL) |
| Tripeptdyl peptidase I |
Late infantile (cLINCL) |
| |
neuronal ceroid lipofuscinosis |
| |
DYSMORPHOLOGY SCREEN
|
(send an urine sample as well) |
| Enzyme |
Disorder |
| beta-galactosidase |
GM1 gangliosidosis |
| Arylsulphatase A |
Multiple sulphatidosis |
| alpha-fucosidase |
Fucosidosis |
| alpha-mannosidase |
alpha-mannosidosis |
| alpha-neuraminidase |
Sialidosis |
| beta-galactosidase |
Galactosialidosis |
| I-cell screen |
I-cell (Mucolipidosis II) |
| beta-glucuronidase |
MPS VII – Sly |
+Chitotriosidase |
|
| |
LIVER & SPLEEN SCREEN |
| Enzyme |
Disorder |
| beta-glucosidase |
Gaucher disease |
| Sphingomyelinase |
Niemann Pick A and B |
| beta-galactosidase |
GM1 gangliosidosis |
| alpha-fucosidase |
Fucosidosis |
| alpha-mannosidase |
alpha-mannosidosis |
| alpha-neuraminidase |
Sialidosis |
| I-cell screening |
I-cell (Mucolipidosis II) |
| beta-glucuronidase |
MPS VII – Sly |
| beta-mannosidase |
beta-mannosidosis |
+ Chitotriosidase |
|
| |
CHERRY RED SPOT & NEUROREGRESSION SCREEN |
| Enzyme |
Disorder |
| b-hexosaminidase Total/A |
GM2 gangliosidosis |
| Sialic acid (Total & Free): Urine |
Sialic acid storage disorder |
| beta-glucosidase |
Gaucher’s disease |
| Sphingomyelinase |
Niemann Pick disease (A/B) |
| beta-galactosidase |
GM1 gangliosidosis |
Which samples are needed?
Most of the enzyme study is done from leucocytes, fibroblasts or plasma samples. It require about 5 – 8 cc blood in EDTA vial. We also request to send us 10-15 cc of urine and clear plasma as well for additional study. |
