Glycogen/lysosomal storage diseases

Question 1

Glycogen storage diseases

Answer 1

type I - Von Gierke disease
type II - Pompe disease
type III - Cori disease
type IV - McArdle disease
12 types total, all result in abnormal glycogen metabolism and an accumulation of glycogen within cells

Question 2

type I - Von Gierke disease

Answer 2

FINDINGS - severe fasting hypoglycemia, ^^ glycogen in liver, ^ blood lactate, ^ TG, ^ uric acid and hepatomegaly
DEFICIENT ENZYME - glucose 6 phosphate
INHERITENCE - AR
OTHER - Tx: frequent oral glucose/cornstarch; avoidance of fructose and galactose

Question 3

type II - Pompe disease

Answer 3

FINDINGS - cardiomegaly, hypertrophic cardiomyopathy, exercise intolerance, systemic findings leading to early death
DEFICIENT ENZYME - lysosomal a-1,4-glucosidase (acid maltase)
INHERITENCE - AR
OTHER - pompe trashes the pump (heart liver and muscle)

Question 4

type III - Cori disease

Answer 4

FINDINGS - milder form of type I with normal blood lactate levels
DEFICIENT ENZYME - debranching enzyme (a-1,6-glucosidase)
INHERITENCE - AR
OTHER - gluconeogenesis intact

Question 5

type IV - McArdle disease

Answer 5

FINDINGS - ^ glycogen in muscle but muscle cannot break it down -> painful muscle cramps, myoglobinuria (red urine) with strenuous exercise and arrhythmia from electrolyte abnormalities
DEFICIENT ENZYME - skeletal muscle glycogen phosphorylase (myophosphorylase)
INHERITENCE - AR
OTHER - blood glucose levels typically unaffected, Tx - vitamin B6 (cofactor)

Question 6

lysosomal storage disease

Answer 6

each caused by a deficiency in one of the many lysosomal enzymes, results in an accumulation of abnormal metabolic products
SPHINGOLIPIDOSES: Fabry, Gaucher, Neimann Pick, Tay Sachs, Krabbe, metachromatic leukodystrophy
MUCOPOLYSACCHARIDOSES: hurler, hunter

Question 7

Fabry

Answer 7

FINDINGS - peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease, HTN
ENZYME DEFICIENT - a-galactosidase A
ACCUMULATED SUBSTRATE - ceramide trihexoside
INHERITANCE - XLR

Question 8

Gaucher

Answer 8

MOST COMMON
FINDINGS - HSM, pancytopenia, OP, aseptic necrosis of femur, bone crises, gaucher cells (lipid laden macrophages resembling crumpled tissue paper) Tx: recombinant glucocerebrosidase
ENZYME DEFICIENT - glucocerebrosidase (b-glucosidase)
ACCUMULATED SUBSTRATE - glucocerebroside
INHERITANCE - AR

Question 9

Neimann Pick

Answer 9

FINDINGS - progressive neurodegeneration (cerebellar dysfunction), HSM, foam cells (lipid laden macrophages), cherry red spot on macula
ENZYME DEFICIENT - sphingomyelinase
ACCUMULATED SUBSTRATE - sphingomyelin
INHERITANCE - AR

Question 10

Tay Sachs

Answer 10

FINDINGS - progressive neurodegeneration, developmental delay, cherry spot on macula, lysosomes with onion skin, NO HSM
ENZYME DEFICIENT - hexosaminidase A
ACCUMULATED SUBSTRATE - GM2 ganglioside
INHERITANCE - AR

Question 11

Krabbe

Answer 11

FINDINGS - peripheral neuropathy, developmental delay, optic atrophy, globoid cells
ENZYME DEFICIENT - galactocerebrosidase
ACCUMULATED SUBSTRATE - galactocerebroside, psychosine
INHERITANCE - AR

Question 12

Metachromatic leukodystrophy

Answer 12

FINDINGS - central and peripheral demyelination with ataxia, dementia
ENZYME DEFICIENT - arylsulfatase A
ACCUMULATED SUBSTRATE - cerebroside sulfate
INHERITANCE - AR

Question 13

Hurler

Answer 13

FINDINGS - developmental delay, gargoylism, airway obstruction, corneal clouding, HSM
ENZYME DEFICIENT - a-L-iduronidase
ACCUMULATED SUBSTRATE - heparan sulfate, dermatan sulfate
INHERITANCE - AR

Question 14

Hunter

Answer 14

FINDINGS - mild hurler + aggressive behavior, no corneal clouding, earlier onset
ENZYME DEFICIENT - iduronate sulfatase
ACCUMULATED SUBSTRATE - heparan sulfate, dermatan sulfate
INHERITANCE - XLR