Storage Disorders

Glycogen storage diseases

4 Diseases are Autosomal recessive Very Poor Carbohydrate Metabolism

Disease Deficient Enzyme Description Treatment
- Symptoms:
1- Severe fasting hypoglycemia 1- Frequent oral glucose/cornstarch
Von Gierke disease Glucose-6-phosphatase 2- Hepatomegaly 2- Avoidance of fructose & galactose.
(type I) 3-  glycogen in liver
4-  blood lactate
Pompe disease - Symptoms:
(type II) Lysosomal a-1,4-glucosidase
1- Cardiomyopathy
Pompe trashes the Pump (acid maltase)
2- Systemic findings leading to early death
(heart, liver, and muscle).
- Symptoms:
Cori disease Debranching enzyme 1- Milder form of type I with normal blood lactate levels
(type III) (a-1,6-glucosidase) 2- Gluconeogenesis is intact
- Symptoms:
McArdle disease  glycogen in muscle, but cannot break it down, leading to :
(type V) Skeletal muscle glycogen 1- Painful muscle cramps,
Phosphorylase (myophosphorylase) 2- Myoglobinuria(red urine) with strenuous exercise
McArdle = Muscle.
3- Arrhythmia from electrolyte abnormalities.
Lysosomal storage diseases
Each is caused by a deficiency in one of the many lysosomal enzymes. Results in an accumulation of abnormal metabolic products.

Sphingolipidoses
Diseases Inheritance Deficient Enzyme Accumulated substance Findings
1- Cardiovascular/renal disease
Fabry disease X-linked recessive a-galactosidase A Ceramide trihexoside 2- Angiokeratomas
3- Peripheral neuropathy of hands/feet
Gaucher disease (Most Glucocerebrosidase 1- Hepatosplenomegaly
common) Glucocerebroside 2- aseptic necrosis of Femur
(B-glucosidase)
3- Bone Crises
Ttreatment : 4- Pancytopenia
recombinant 5- Gaucher cellsA(lipidladen macrophages resembling
glucocerebrosidase. crumpled tissue paper)

Niemann-Pick disease 1- Hepatosplenomegaly

2- Progressive Neurodegeneration
Autosomal Recessive Sphingomyelinase Sphingomyelin 3- “Cherry-red” spot on macula
4- Foam cells (lipidladen macrophages) B
Tay-Sachs disease 1- NO hepatosplenomegaly (vs. Niemann-Pick)
2- Progressive Neurodegeneration
Hexosaminidase A GM2 ganglioside 3- Cherry-red” spot on macula C
4- Developmental delay
5- Lysosomes with onion skin
1- Optic atrophy
- Galactocerebroside 2- Peripheral neuropathy
Krabbe disease Galactocerebrosidase
- Psychosine 3- Developmental delay
4- globoid cells
Metachromatic 1- Central and peripheral Demyelination with ataxia
Arylsulfatase A Cerebroside sulfate
leukodystrophy 2- Dementia
Mucopolysaccharidoses
1- Hepatosplenomegaly
Hurler syndrome Autosomal Recessive 2- Airway obstruction
a-L-iduronidase - Heparan sulfate 3- Corneal clouding
- Dermatan sulfate 4- Developmental delay
5- Gargoylism
Hunter syndrome Iduronate sulfatase Mild Hurler + aggressive behavior, NO corneal clouding
X-linked recessive