glycolipid disorders

Question 1

What are lysosomes

Answer 1

Garbage centers in cells that are acidic, contain about 50 hydrolase enzymes that break down macromolecules into smaller components

Question 2

How are hydrolases targeted to the lysosome

Answer 2

Mannose-6-phosphate on surface of hydrolases bind to M6P receptors

Question 3

what is a lysosomal storage disease

Answer 3

Occurs when lysosomal enzyme is missing/deficient resulting in substrate accumulation in various organs

Question 4

Signs of LSD in brain vs other organs

Answer 4

brain: neurodegeneration. Other organs: increase in mass

Question 5

Inheritance pattern of MOST lysosomal storage diseases

Answer 5

autosomal recessive

Question 6

List the X-linked lysosomal storage diseases

Answer 6

1. Fabry disease (alpha-galactosidase). 2. Hunter syndrome (iduronate-2-sulfatase). 3. Danon disease (lysosomal associated membrane protein 2)

Question 7

What is the main problem in lysosomal storage diseases

Answer 7

Gradual accumulation that slowly leads to storage and dysfunction. The accumulating substrate is usually not toxic

Question 8

time course of lysosomal storage diseases

Answer 8

Progressive disease that present less acutely than many other metabolic conditions

Question 9

Symptoms of LSD in brain

Answer 9

macrocephaly, cognitive regression, seizures, ataxia

Question 10

Symptoms of LSD in eyes

Answer 10

corneal clouding, cherry red spot in retina (Tay Sachs)

Question 11

Symptoms of LSD in ear/nose/throat

Answer 11

macroglossia, sleep apnea

Question 12

Symptoms of LSD in liver

Answer 12

hepatosplenomegaly- can be massive, with protuberant belly. Typically does not lead to LFT abnormalities

Question 13

Symptoms of LSD in kidneys

Answer 13

Progressive renal failure and proteinuria (Fabry disease)

Question 14

Symptoms of LSD in skeletal system

Answer 14

dysostosis multiplex (vertebral breaking, abnormal bony structure on x ray), joint stiffness, short stature

Question 15

Symptoms of LSD in skin

Answer 15

coarseness/thickening

Question 16

Gaucher type 1 presentation

Answer 16

Adult onset and increased incidence in Ashkenazi jews- fatigue, bone pain, hepatosplenomegaly

Question 17

Gaucher type 1 labs/ histology

Answer 17

anmia, thrombocytopenia, gaucher cells (macrophages) in bone marrow

Question 18

gaucher type 1 imaging

Answer 18

avascular necrosis in bones, erlenmeye flask deformity (x ray of distal femur)

Question 19

Gaucher type 1 enzyme deficiency and treatment

Answer 19

Beta glucosidase (aka glucocerebrosidase) deficiency results in build up of glucosylceramides. Treated with imiglucerase, but pts will not die from this dz usually even if untreated

Question 20

Tay Sachs type 1 presentation

Answer 20

infantile or early childhood. Increased in Ashkenzi jews. Blindness, seizures, increased startle reflex, mental/motor deterioration.

Question 21

Tay Sachs type 1 exam/ histology

Answer 21

Cherry red spot in eye Lipid loaded cells

Question 22

Tay Sachs enzyme deficiency and treatment

Answer 22

Beta-hexosaminidase A deficiency. Treatment is supprtive and pts will likely die

Question 23

Fabry disease presentation

Answer 23

Pre-teen/teen w/ acroparathesias or in adult with renal failure/ angiokeratomas or older adult with left ventricular hypertrophy or stroke.

Question 24

Fabry disease clinical sx

Answer 24

acroparesthesia (pain in palms/soles, especially with fevers), dark red angiokeratomas in bathing suit distribution, LVH/stroke, proteinuria and renal failure

Question 25

family history in Fabry disease

Answer 25

renal failure in males

Question 26

Fabry disease enzyme deficiency and treatment

Answer 26

Alpha-galactosidase. Treated with agalsidase beta

Question 27

Pompe disease presentation

Answer 27

Infantile: present at 3-6 months; dead at 1 year (w/o Rx). Childhood: not likely tested on. Adult: slowly progressive muscle weakness

Question 28

Pompe disease clinical sx

Answer 28

Infant with progressive muscle weakness (floppy) and LVH. Adult with proximal muscle weakness and respiratory weakness (sleep apnea)

Question 29

Pompe disease labs/imaging

Answer 29

Elevated CK; glycogen on muscle biopsy

Question 30

Pompe disease enzyme deficiency and treatment

Answer 30

alpha-glucosidase deficiency resulting in elevated glycogen. Treated with alglucosidase alfa

Question 31

Hunter disease presentation

Answer 31

childhood- coarse facies, airway dz, ear infection, NO corneal clouding, hearing loss

Question 32

Hunter disease enzyme deficiency and treatment

Answer 32

iduronate sulfatase. Treatment: idursulfase

Question 33

Hurler syndrome presentation

Answer 33

childhood- coarse facies, airway dz, ear infections, corneal clouding, hearing loss

Question 34

Hurler syndrome enzyme deficiency and treatment

Answer 34

alpha iduronidase. Treatment: iaronidase

Question 35

mucopolysaccharidoses are caused by

Answer 35

defects in degradation of proteoglycans

Question 36

McArdle disease presentation

Answer 36

adults- muscle weakness and cramping, often exercise related cramping and myogolbuinuria (coffee colred urine after exercise)

Question 37

McArdle disease labs

Answer 37

high CK

Question 38

McArdle disease enzyme deficiency and treatment

Answer 38

glycogen phosphorylase- treated with support