Ans.c (Sphingomyelinase) (Ref. Harper Biochemistry, 26th ed. 203; Table 24-1; OP Ghai 6th ed. 542, 616) SphingolipidosesInheritanceEnzyme DeficientCNS InvolvementVisceral Involvement1Fabry diseaseXLRAlpha-Galactosidase_+2Krabbe's diseaseARBeta-Galactosidase++3Farber diseaseARCeramidase+/--4Gaucher diseaseARBeta-Glucosidase+/-+5Metachromatic leukodystrophyARSulfatide sulfatase+-6Niemann-pick diseaseARSphigomyelinase++7Tay-sachs diseaseARHexosaminidase A+-8Sandhoff diseaseARHexosaminidase A,B++# NIEMANN-PICK DISEASE- Due to deficiency of sphingomyelinase- Stored material = sphingomyelin- C/f:* Enlarged liver and spleen,* Mental retardation,* Cherry-red spots,* Foam cells in blood,* Pulmonary infiltrates.# GAUCHER'S DISEASE- Due to deficiency of Acid b-Glucosidase- Stored material = Glucosylceramide- C/f:* Enlarged liver and spleen,* MR,* Erosion of long bones (Pathological of bones)* Foam cells in blood.# VON-GIERKE'S DISEASE (Type I - glycogenosis)- Due to deficiency of glu-6-phosphatase- C/f:* Growth retardation,* Liver and kidney enlarged due to increased glycogen content,* Hypoglycemia,* Hyperuricemia,* Hyper lipidemia, and* Lactate acidosis.Selected Lysosomal Storage DiseasesDisorderEnzyme Deficiency Stored MaterialInheritanceNeurologicLiver Spleen Enlarg- mentSkeletal DysplasiaOphthalmo- logicUnique featuresMucopolysaccharidoses (MPS)MPSIHHurleralpha-L-Iduro- nidase Dermatan sulfate Heparan sulfateARMental retardation Mental retardation None++++ + + +Corneal cloudingCoarse facies; cardiovascular involvement; joint stiffnessMPS II, HunterIduronate sulfataseDermatan sulfate Heparan sulfateX-linkedMental retardation, less in mild form++++ + + +Retinal degenera- tion, no corneal cloudingCoarse facies; cardiovascular involvement; joint stiffness; distinctive pebbly skin lesionsMPS III A, Sanfilippo AHeparan-N- sulfataseHeparan sulfateARSevere mental retardation++NoneMild coarse faciesMPS III B, Sanfilippo BN-Acetyl-a- glucosaminidaseHeparan sulfateARSevere mental retardation++NoneMild coarse faciesMPS III C, Sanfilippo CAcetyl-CoA: a- glucosaminide N-acetyltrans- feraseHeparan sulfateARSevere mental retardation++NoneMild coarse faciesMPS IIID, Sanfilippo DN-Acetylglucosa- mine-6-sulfate sulfataseHeparan sulfateARSevere mental retardation++NoneMild coarse faciesMPS IV A, MorquioN-Acetylgalacto- samine-6-sulfate sulfataseKeratan sulfate Chondroitin-6 sulfateARNone++ + + +Corneal cloudingDistinctive skeletal deformity; odontoid hypoplasia; aortic valve diseaseMPS VI B, Morquiob-Galactosidase ARNone+-+ + + + MPS VI,Maroteaux- LamyArylsulfatase BDermatan sulfateARNone+++ + + +Corneal cloudingCoarse facies; valvular heart diseaseMPS VIIb-GlucuronidaseDermatan sulfate Heparan sulfateARMental retardation, absent in some adults++++++Corneal cloudingCoarse facies; vascular involvement; hydrops fetalis in neonatal formGM2 GangliosidosesTay-Sachs diseaseb-Hexosamini- dase AGM2 gangliosidesARMental retardation; seizures; later juvenile formNoneNoneCherry red spot in infantile formMacro-cephaly; hyperacusis in infantile formSandhoff's- diseaseb-Hexosamini- dases A and BGM2 gangliosidesARMental retardation; seizures+++-Cherry red spotMacro-cephaly; hyperacusis Neutral GlycosphingolipidosesFabry'sDiseasea-Galactosi- dase AGlobotriaosyl- ceramideX-linkedPainfulAcropares- thesiasNoneNoneCorneal dystrophy, vascular lesionsCutaneous angiokeratomas; hypo- hydrosisGaucher's diseaseAcid b-glucosi- daseGlucosyl- ceramideARNone+ + + ++ + + +NoneAdult form highly variableGaucher's cells in bone marrow; cytopenias++++++++Eye movements+++ + + ++ + + + Niemann- Pick disease A and BSphingomye - linaseSphingo- myelinARMental retardation; seizures+ + + +None Osteopo- rosisMacular degenerationPulmonary infiltrates Lung failure Foam cells in bone marrowLeukodystrophiesKrabbe's diseaseGalactosyl- ceramidaseGalactosy-IceramideGalactosyls- phingosineARMental retardationNoneNoneNoneWhite matter globoid cellsMetachro- matic leukody - strophyArylsulfatase ACerebroside sulfateARMental retardation; dementia; and psychosis in adultNoneNoneOptic atrophyGait abnormalities in late infantile formMultiple sulfatase deficiencyActive site cysteine to C-a formylglycineconverting enzymeSulfatides; mucopoly - saccharidesARMental retardation+++Retinal degenerationAbsent activity of ail known cellular sulfatasesDisorders of Neutral LipidsWolman's diseaseAcid lysosomal lipaseCholesteryl esters; triglyceridesARMild mental retardation+++NoneNoneAdrenal calcificationCholesteryl ester storage diseaseAcid lysosomal lipaseCholesteryl estersARNoneHepato - megalyNoneNoneFatty liver disease; cirrhosisFarber's diseaseAcid ceramidaseCeramideAROccasional mental retardation+NoneMacular degenerationArthropathy, subcutaneous nodulesDisorders of GlycogenPompe's diseaseAcid a-glucosidaseGlycogenARNeuromuscular+-NoneNoneMyocar-diopathy