Glycogen and Lysosomal Storage Diseases

Question 1

Von Gierke disease (Type I)

Answer 1

Deficient enzyme: Glucose-6-phosphatase

Findings: Severe fasting hypoglycemia, increased glycogen in the liver, increased blood lactate levels, increased triglycerides, increased uric acid, and hepatomegaly.

AR

Treatment: frequent oral glucose, avoidance of fructose and galactose.

Question 2

Pompe disease (Type II)

Answer 2

Deficient enzyme: Lysosomal alpha-1,4-glucosidase

Findings: Cardiomegaly, hypertrophic cardiomyopathy, exercise intolerance, systemic findings lead to early death

AR

Muscle biopsy will show accumulation of glycogen in lysosomes.

“Pompe trashes the Pump” (heart, liver, and muscle)

Question 3

Cori disease (Type III)

Answer 3

Deficient enzyme: Debranching enzyme (alpha-1,6-glucosidase)

Findings: Milder form of type I with normal blood lactate levels.

AR

Gluconeogenesis is intact

Question 4

McArdle disease (Type V)

Answer 4

Deficient enzyme: skeletal muscle glycogen phosphorylase (myophosphorylase)

Findings: increased glycogen in muscle, but muscle cannot break it down. Leads to muscle cramps, myoglobinuria with strenuous activity, and arrhythmias from electrolyte abnormalities.

AR

Treatment: vitamin B6

Blood glucose levels usually unaffected

Question 5

Fabry Disease

Answer 5

Deficient enzyme: alpha-galactosidase A

Accumulated substrate: ceramide trihexoside

Findings: peripheral neuropathy of hands and feet, angiokeratomas, cardiovascular/renal disease

Question 6

Gaucher Disease

Answer 6

Deficient enzyme: Glucocerebrosidase (beta-glucosidase)

Accumulated substrate: glucocerebroside

Findings: most common. HSM, pancytopenia, osteoporosis, aseptic necrosis of femur, bone crises, gaucher cells (lipid laden macrophages resembling crushed tissue paper).

Treatment: recombinant glucocerebrosidase

Question 7

Niemann-Pick Disease

Answer 7

Deficient enzyme: Sphingomyelinase

Accumulated substrate: sphingomyelin

Findings: Progressive neurodegeneration, HSM, foam cells, cherry red spot on macula

Question 8

Tay-Sachs Disease

Answer 8

Deficient enzyme: Hexosaminidase A

Accumulated substrate: GM2 ganglioside

Findings: Progressive neurodegeneration, developmental delay, cherry red spot on macula, lysosomes with onion skin, no HSM.

Question 9

Krabbe Disease

Answer 9

Deficient enzyme: Galactocerebrosidase

Accumulated substrate: galactocerebroside, psychosine

Findings: Peripheral neuropathy, developmental delay, optic atrophy, globoid cells

Question 10

Metachromatic leukodystrophy

Answer 10

Deficient enzyme: Arylsulfatase A

Accumulated substrate: cerebroside sulfate

Findings: Central and peripheral demyelinatio n with ataxia, dementia

Question 11

Hurler Syndrome

Answer 11

Deficient enzyme: alpha-L-iduronidase

Accumulated substrate: heparan sulfate, dermatan sulfate

Findings: Developmental delay, gargoylism, airway obstruction, corneal clouding, HSM

Question 12

Hunter Syndrome

Answer 12

Deficient enzyme: Iduronate sulfatase

Accumulated substrate: heparan sulfate, dermatan sulfate

Findings: Milder Hurler + aggressive behavior, no corneal clouding