USMLE Lysosomal/Glycogen

• Very Poor Carbohydrate Metabolism!
• Von Gierke's (G-6-Phosphatase Deficiency)
• Pompe's Disease (Lysosomal alpha-1,-4 glucosidase deficiency)
• Cori's Disease (Debranching alpha-1-6-glucosidase deficiency)
• McArdle's (Skeletal muscle glycogen phosphorylase deficiency)

• Very Poor Carbohydrate Metabolism
• Glycogen Storage Disease
• Glucose-6-Phosphatase Deficiency.
• Severe fasting hypoglycemia.
• Hepatomegaly because you can't get glucose out of liver.

• Very Poor Carbohydrate Metabolism
• Lysosomal alpha-1-4-glucosidase deficiency

Cardiomegaly and systemic finding leads to early death.

Pompe's trashes the pump!

• Very Poor Carbohydrate Metabolism
• Glycogen Storage Disease

alpha-1-6-glucosidase debranching enzyme. Basically a milder form of Von Gierke's disease, with fasting hypoglycemia. But gluconeogenesis is intact.

• Type V Glycogen Storage Disease
• Skeletam Muscle Glycogen Phosphorylase.
• Cannot break down Glycogen in Skeletal muscle.
• Leads to painful muscle cramps and myoglobinuria with strenous exercise. No lactic acid in muscle (because don't have any glucose to break down!).

• Deficiency: Hexosaminidase A
• Sachs but a Hex on Polio
• Accumulated Substance: GM2 gangliosides
• Findings: Progressive neurodegeneration, developmental delay, cherry-red spot on macula, lysosomes with onion skin (whorled membranes). Unlike Niemann-Pick, no hepatospleomegaly.
• Autosomal Recessive

• Deficient Enzyme: Sphingomyelinase
• Accumulated Substance: Sphingomyelins
• Findings: Niemann-Pick hings on hepatosplenomegaly.
• other findings include: cherry-red spot on macula, foam cells (macrophages) progressive neurodegeneration, mental retardation, microcephaly.
• Autosomal Recessive

• Deficient Enzyme: Beta-glucocerebrosidase
• Accumulation: Glucerobrosides
• Autosomal Recessive
• Findings: Hepatosplenomegaly, Bone Involvement (Gaucher makes you grouchy), pain and fracture (asceptic necrosis of femor.
• Gaucher cells are enlarged macrophages with fibrillary cytoplasm (macrophages that look like crumpled tissue paper).

• Deficient enzyme: alpha-galactosidase A
• Accumualted Substance: Ceramide trihexoside
• X-linked Recessive
• X-linked think milk (alpha-galactosidase deficiency)
• Findings: Peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease

• Deficient Enzyme: Galactocerebrosidase
• Accumulated Substance: Galactocerebroside
• Autosomal Recessive
• Peripheral Neuropathy, developmental delay, optic atrophy, globoid cells.

Unlike Fabry, it has optic involvement and developmental delay. Not having eyes and being slow development makes you Krabbe!

• Deficient Enzyme: Arylsulfatase A
• Accumulated Substance: Cerebroside sulfate
• Autusomal Recessive

Central and peripheral demyelination with ataxia and dementia.

• Don't have lysosomal enzymes to break down glycosaminoglycan's!
• Hurler's syndrome,
• Hunter's Disease

• Deficient: alpha-L-iduronidase
• Accumulated: Glycosaminoglycans, Heparan and dermatan sulfate
• Autosomal recessive.

Developmental delay, gargoylism (coarse facial features, Hurler), airway obstruction, corneal clouding, hepatosplenomegaly.

• Deficient enzyme: iduronate sulfatase.
• Accumulating: Heparan and dermatan sulfate (glycosaminoglycans)
• X-linked recessive.

Hunter's see clearly (no corneal clouding) and aim for the X (x-linked recessive).

They have mild Hurler's with agressive behavior!

Tay-Sachs, Niemann-Pick, and some forms of Gaucher's.