Lysosomal and Glycogen Storage Diseases

Question 0

Gaucher Disease - Findings/Enzyme/Substrate/Genetics

Answer 0

Lysosomal - Sphingolipidoses - AR - Most Common
Findings - Hepatosplenomegaly + Pancytopenia + Bone Crisis + Gaucher Cells (Lipid-Laden Macrophages)
Enzyme/Substrate - Glucocerebrosidase (B-Glucosidase) - Glucocerebroside
Treatment - Recombinant Glucocerebrosidase
Tre

Question 1

Farby Disease - Findings/Enzyme/Substrate/Genetics

Answer 1

Lysosomal - Sphingolipidoses - XR
Findings - Peripheral Neuropathy + CVD + Renal Disease
Enzyme/Substrate - A-Galactosidase A - Ceramide/Trihexoside

Question 2

Niemann Pick - Findings/Enzyme/Substrate/Genetics

Answer 2

Lysosomal - Sphingolipidoses - AR
Findings - Progressive neurodegeneration - hepatosplenomegaly - cherry red spot on macula + foam cells
Enzyme/Substrate - Sphingomyelinase - Sphingomyelin

Question 3

Tay-Sachs Disease Findings/Enzyme/Substrate/Genetics

Answer 3

Lysosomal - Sphingolipidoses - AR
Progressive - Neurodegeneration + Cherry red spot on macula - BUT NO hepatosplenomegaly ***
Enzyme/Substrate - Hexosaminidase A - GM2 Ganglioside

Question 4

Krabbe Disease - Findings/Enzyme/Substrate/Genetics

Answer 4

Lysosomal Sphingolipidosis - AR
Findings - Peripheral Neuropathy - Developmental Delay + Optic Atrophy + Globoid cells
Enzyme/Substrate - Galactocerebrosidase + Galactocerebroside

Question 5

Hurler Syndrome - Findings/Enzyme/Substrate/Genetics

Answer 5

Lysosomal - Mucopolysaccharidoses - AR
Findings - Developmental Delay + Gargoylism + Airway Obstruction + Hepatosplenomegaly + CORNEAL CLOUDING****
Enzyme/Substrate - Alpha-1 Iduronidase - Heperan/Dermatan Sulfate

Question 6

Hunter Syndrome - Findings/Enzyme/Substrate/Genetics

Answer 6

Lysosomal Mucopolysaccharidoses - XR
Findings - Milder Hurler + Aggression + NO CORNEAL CLOUDING**
Enzyme/Substrate - Iduronante Sulfatase + Heperan/Dermatan Sulfate
Hunters see clearly (no corneal clouding) to hit the X

Question 7

Von Gierke Disease - Findings/Enzyme/Substrate/Genetics

Answer 7

Glycogen Storage - Type 1 - AR
Findings - Sever fasting glucose + high glycogen in the liver + blood lactate + hepatosplenomegaly
Enzyme/Substrate - Glucose-6-Phosphatase Deficiency (Opposite Hexokinase)

Question 8

Pompe Disease - Findings/Enzyme/Substrate/Genetics

Answer 8

Glycogen Storage Type II - AR - Lysosomal
Findings - Cardiomyopathy + Systemic findings (early death)
Enzyme - Lysosomal Alpha 1-4 Glucosidase
Pompe trashes the pump (heart + liver + muscle)

Question 9

Cori Disease - Findings/Enzyme/Substrate/Genetics

Answer 9

Glycogen Storage Type 3 - AR
Findings - Milder form of Type 1 (Von Gierke) with normal lactate levels
Enzyme - Debranching Enzyme (A 1-6 Glucosidase)

Question 10

McArdle Disease - Findings/Enzyme/Substrate/Genetics

Answer 10

Glycogen Storage Disease - Type 5 - AR
Findings - High muscle glycogen + muscle pain + exercise intolerance cramps
Enzyme - Skeletal Muscle Glycogen Phosphorylase
McArdle - Muscle

Question 11

Her’s Disease - Findings/Enzyme/Substrate/Genetics

Answer 11

Glycogen Storage Disease - Type 6
Findings - High liver glycogen + hypoglycemia (milder type 1)
Enzyme - Hepatic Glycogen Phosphorylase

Question 12

Treatment Therapies for LSDs (5)

Answer 12

1) Allogenic Bone Marrow Transplant - Hurlers (Augmentation)
2) Enzyme Replacement Therapy (ERT) - Gaucher (Augmentation)
3) Substrate Reduction Therapy (SRT) - Uses Muglustate to inhibit glycosphingolipid production - Gaucher + Farby
4) Enzyme Enhancement Therapy - Trial Stages
5) Chaperone Therapy - Used in Farby