Metabolic Disorders key words

Question 1

Coarse facial features, macroglossia, short stature

Answer 1

storage disease

Question 2

Ernlemeyer Flap (looks like erlenmeyer flask)

Answer 2

Gaucher Disease Type I

Question 3

cherry red spot in eye

Answer 3

Tay Sachs Disease

Question 4

hepatosplenomegaly, ,wplenectomy, bone/joint pain with foamy macrophages

Answer 4

Gaucher Disease

Question 5

Mucopolysaccharidoses are inherited storage disease caused by

Answer 5

defects in degradation of proteoglycans (not insufficient proteolytic enzymes)

Question 6

infant died with progressive muscle weakness, cardiac involvement (cardiomyopathy)

Answer 6

Pompe disease

Question 7

proteinuria and acroparasthesias

Answer 7

Fabry disease

Question 8

deficient enzyme in Fabry disease

Answer 8

alpha-galactosidase A

Question 9

enzyme deficient in Gaucher disease

Answer 9

glucocerebrosidase (B-glucosidase)

Question 10

enzyme deficient in Niemann-Pick dz

Answer 10

sphingomyelinase

Question 11

enzyme deficient in Tay Sachs

Answer 11

Hexosaminidase A

Question 12

enzyme deficient in Krabbe disease

Answer 12

Galactocerebrosidase

Question 13

enzyme deficient in Metachromatic leukodystrophy

Answer 13

arylsulfatase A

Question 14

enzyme deficient in Hurler syndrome

Answer 14

alpha-L-iduronidase

Question 15

enzyme deficient in Hunter syndrome

Answer 15

Iduronate sulfatase

Question 16

how are most lysosomal storage disorders inherited

Answer 16

autosomal recessive, except Fabry and Hunter (X-linked);

also a new Danon Disease – super rare/new and unlikely on USMLE

Question 17

most common lysosomal storage disorder

Answer 17

Gaucher disease

Question 18

which population has increased incidence of Tay Sachs, Niemann-Pick, and some Gaucher disease forms

Answer 18

Ashkenazi Jews

Question 19

adult onset, big liver/spleen, anemia/low platelets

Answer 19

Gaucher Type I

Question 20

cherry red spot (classic), increased startle reflex, normal liver/spleen

Answer 20

Tay Sachs type I

Question 21

Angiokeratomas, Renal failure, acroparesthesias, normal IQ

Answer 21

Fabry

Question 22

Gaucher Type I treatment

Answer 22

enzyme replacement and substrate inhibition- beta glucosidase (glucocerebrosidase)

Question 23

Fabry Disease Treatment

Answer 23

FDA approved enzyme replacement and substrate inhibition

Question 24

adult male with angiokeratomas + acroparesthesias +fam hx renal failure in males

Answer 24

Fabry

Question 25

Supranuclear gaze palsy (vertical gaze palsy), cherry red spot, BIG hepatosplenomegaly

Answer 25

Niemann-Pick Type I

Question 26

Does Tay Sachs have enlarged liver/spleen

Answer 26

NO

Question 27

Which storage diseases have enlarged liver/spleen

Answer 27

Gaucher type I, Hunter, Hurler, Sandhoff, Niemann-Pick

Question 28

Infant with profound weakness and hypertrophic cardiomyopathy

Answer 28

Pompe Disease

Question 29

Pompe treatment

Answer 29

FDA approved enzyme replacement and substrate inhibition

Question 30

Adult with proximal muscle weakness and slep apnea

Answer 30

Pompe disease

Question 31

Coarse-appearing child who is short, hoarse voice, frequent URIs and some learning problems; NO corneal clouding

Answer 31

Hunter

Question 32

coarse facies, big liver/spleen, major skeletal problems, corneal clouding

Answer 32

Hurler disease

Question 33

Hunter treatment

Answer 33

enzyme replacement and substrate inhibition (Iduronate sulfatase)

Question 34

Hurler treatment

Answer 34

FDA approved enzyme replacement and substrate inhibition (alpha iduronidase)

Question 35

Muscle cramping after exercise, myoglobinuria (coffee colored urine after exercise); normal cognition, chronic condition

Answer 35

McArdle Disease

Question 36

enzyme defect in McArdle Disease

Answer 36

Glycogen phosphorylase

Question 37

Lysosomes

Answer 37

garbage (or recycling) centers in cells that are acidic, contain about 50 hydrolase enzymes, that break down macromolecules into smaller components

Question 38

Lysosomal Storage Diseases (LSDs)

Answer 38

defects in lysosomal function present and one or more molecules can't be properly degraded and/or processed. Usually absence of one or more lysosomal enzymes undigested glycolipids and extracellular components accumulate

Question 39

how do storage disorders manifest clinically

Answer 39

increase in mass of affected tissues and organs. When brain affected (often the case), you get neurodegeneration different presentations driven partly by defective enzyme and materials accumulating in which organs.

Question 40

are LSDs more acute or chronic

Answer 40

chronic with gradual accumulation slowly leading to storage and dysfunction; generally present less acutely than other metabolic conditions

Question 41

Which diseases have enzyme replacement available

Answer 41

Fabry, Gaucher, Hurler (MPSI), Hunter (MPSII), Maroteaux-Lamy (MPS IV), Pompe

Question 42

LSD therapy options

Answer 42

supportie, surgery, bone marrow transplant, enzyme replcaement, substrate inhibition, chaperone therapy (stabilize damaged enzyme)

Question 43

facial coarseness

Answer 43

facial thickening, looks a bit swollen

Question 44

brain sxs

Answer 44

cognitive function, behavior, loss of skills

Question 45

skin sxs

Answer 45

coarseness, thickness, hirsutism, angiokeratoma (Fabry)

Question 46

Skull/brain sxs

Answer 46

macrocephaly, hydrocephalus, cognitive regression, ataxia, seizures

Question 47

hearing sxs

Answer 47

hearing loss from otitis media/Eustachian tube dysfunction

Question 48

Ear/Nose/Throat sxs

Answer 48

macroglossia, thickened vocal cords, nasal congestion, sleep apnea (complication)

Question 49

heart sxs

Answer 49

cardiomyopathy, arrhythmia, thickened heart valves

Question 50

lungs sxs

Answer 50

airway narrowing, pulmonary fibrosis

Question 51

Liver sxs

Answer 51

hepatosplenomegaly with typically preserved hepatic function

Question 52

GI sxs

Answer 52

constipation/diarrhea

Question 53

Kidney sxs

Answer 53

progressive renal failure adn proteinuria (fabry)

Question 54

skeletal sxs

Answer 54

dysostosis multiplex, joint stiffness, short stature

Question 55

muscle

Answer 55

hypotonia, myoclonic jerks, spasticity, weak

Question 56

age of onset for Gaucher

Answer 56

adult

Question 57

age of onset for Tay Sachs type I

Answer 57

infantile/early, early childhood

Question 58

Fabry age of onset

Answer 58

pre-tenn/teen wiht neuro findings or adult with renal failure or older adult with left ventricular hypertrophy or stroke

Question 59

Tay Sachs treatment

Answer 59

supportive

Question 60

Pompe treatment

Answer 60

alglucosidase alpha

Question 61

Fabry treatment

Answer 61

agalsidase beta