88 SEC TION II Biochemistry   

B IOCHEMISTRY—Metabolism

Lysosomal storage Each is caused by a deficiency in one of the many lysosomal enzymes. Results in an accumulation
diseases of abnormal metabolic products.
DISEASE FINDINGS DEFICIENT ENZYME ACCUMULATED SUBSTRATE INHERITANCE
Sphingolipidoses
Tay-Sachs disease Progressive neurodegeneration, HeXosaminidase A GM2 ganglioside AR
A developmental delay, hyperreflexia, (“TAy-SaX”) Tay is a baby who has been Hexed to deliver Onions in a GM jeep.
The hex has caused him Confusion and his eyes are Red
hyperacusis, “cherry-red” spot on
macula A , lysosomes with onion
skin,NO
no hepatosplenomegaly
Hepatosplenomegaly (vs ( vs Niemann Picks)
Niemann-Pick). Death <2 years
Fabry disease Early: triad of episodic peripheral α-galactosidase A Ceramide XR
B neuropathy, angiokeratomas B , trihexoside
hypohidrosis. ALSO ACUTE HEARING LOSS (globotriaosylce­
Late: progressive renal failure, ramide)
The Galactic Alpha Male can break heart kidney and skin . He has No feelins for his targets.
Dark Red non blanchin maculopapules cardiovascular disease. He gifted all of these 3 Ceramic statues to hex em so that they can suffer worse later
at body folds , umbilical regions.
Metachromatic Central and peripheral demyelination Arylsulfatase A Cerebroside sulfate AR
leukodystrophy with ataxia, dementia. . His cerebrum suffers
ARYL is a Slow man with terrible posture and memory
Krabbe disease Peripheral neuropathy, destruction Galactocerebrosi- Galactocerebroside, AR
of oligodendrocytes, developmental dase (galactosylce- psychosine
IMAGINE MR KRAB FROM
SPONGBOB CARTOON delay, optic atrophy, globoid cells. ramidase)
Psychosine
Gaucher disease Most common.  lucocerebrosidase Glucocerebroside
G AR
C Hepatosplenomegaly, pancytopenia, (β-glucosidase); treat
osteoporosis, Avascular
avascular necrosis
Necrosisof Femur with recombinant
femur, bone crises, Gaucher cells C glucocerebrosidase
(lipid-laden
Lipid macrophages resembling
laden macrophages resemblin
crumpled tissue
Crumpled paper).
Tissue Paper

Niemann-Pick disease Progressive neurodegenera­tion, Sphingomyelinase Sphingomyelin AR

D hepatosplenomegaly, foam cells
(lipid-laden
Lipid macrophages) D ,
laden macrophages
“cherry-red” spot on macula A .

Hurler is a boy with Big Glassesand Asthma . He is often called a Gargoyle becoz
of Coarse Facial Features and Rigid Body
. Movements They tease him with an L for being a loser.
Mucopolysaccharidoses
Hurler syndrome Developmental delay, gargoylism, α-l-iduronidase Heparan sulfate, AR
I cell dz also has COARSE FACIAL airway obstruction, corneal clouding, dermatan sulfate
FEATURES, kyphoscoliosis and more.
hepatosplenomegaly. Gargoylism = Large skull, abnl shaped ribs and vertebrae.
Hunter syndrome Mild Hurler + aggressive behavior, no Iduronate-2-sulfatase Heparan sulfate, XR
no CLOUDING corneal clouding. dermatan sulfate

Tay Sachs Fabry X linked

GM2 Ceramide trihexoside 1 Triad No man picks (Niemann-Pick) his nose with
1 progressive
neurodegeneration hexoseaminidase A
2 X linked recessive
his sphinger (sphingomyelinase).
2 Cherry red macula
GM3 alpha galactosidase Hunters see clearly (no corneal clouding) and
Sulfatides Gauchers crumpled tissue aggressively aim for the X (X-linked recessive).
Glucocerebroside 1 Adult hepatosplenomegaly
Aryl Sulfatase glucocerebrosidase 2 Avascular necrosed femur  incidence of Tay-Sachs, Niemann-Pick, some
Metachrom Galactocerebroside Ceramide Sphingomyelin forms of Gaucher disease in Ashkenazi Jews.
1 Demylination
galactocerebrosidase Sphingomyelinase
2 Dementia Krabbe's Bloom syndrome also in ASHkenazis but No cherry red macula.
Niemann Picks
1 progressive
neurodegeneration
1 Cherry Red Macula Hepatosplenomegaly Ashkenazi Jews /cherry red mac
2 Hepatospleenomegaly 1 GAUCHER
2 optic atrophy 1 GAUCHER - Adult hepatosplenomegaly
2 NIEMANN PICK
3 NIEMANN PICK - Hepatosplenomegaly
3 HURLER
3 Tay Sachs - No megaly

FAS1_2019_01-Biochem.indd 88 11/7/19 3:16 PM