Glycolipid disorders

Question 1

Lysosomal storage diseases

Answer 1

when a lysosomal enzyme is deficient/missing –> substrate accumulation (storage) in various organs (you can’t get rid of the substrate)

not acutely toxic

Question 2

LSD inheritance

Answer 2

majority = autosomal recessive

3 X-linked diseases: Fabry (alpha-galactosidase), Hunter syndrome (iduronate-2-sulfatase), Danon disease

Question 3

LSD presentation

Answer 3

usually progressive diseases, with less acute presentation than other metabolic diseases

Question 4

Brain LSD manifestations

Answer 4

macrocephaly, cog regression

Question 5

Eye LSD manifestations

Answer 5

corneal clouding, cherry red spot (Tay Sachs or Niemann-Pick)

Question 6

ENT LSD manifestations

Answer 6

macroglossia, sleep apnea

Question 7

Liver LSD manifestations

Answer 7

hepatosplenomegaly c preserved hepatic function

Question 8

Kidney LSD manifestations

Answer 8

progressive renal failure + proteinuria (Fabry disease)

Question 9

Skeletal LSD manifestations

Answer 9

dysostosis multiplex, joint stiffness, short stature

Question 10

What is dysostosis multiplex?

Answer 10

abnormal bony structure on X-rays; vertebral “beaking”, broad bases of metacarpals and phalanges, scoliosis

Question 11

Adult-onset, hepatosplenomegaly, anemia, thrombocytopenia

“foamy macrophages” on microscopy

normal life span, no CNS involvement

Answer 11

Gaucher Type I: deficiency of beta glucosidase (enzyme replacement therapy)

Question 12

Difference in Gaucher 1 and 2

Answer 12

type 2 = infantile, acute, deadly; CNS involvement

Question 13

Infant with increased startle reflex, NO hepatosplenomegaly, cherry red spot

Answer 13

Tay Sachs 1: deficiency of beta-hexosaminidase A. Fatal

Question 14

X-linked disease

children –> acroparasthesias
young adults: proteinuria, angiokeratomas (bathing trunk distribution)

normal IQ

Answer 14

Fabry disease: deficiency of alpha galactosidase (enzyme replacement therapy)

Question 15

presents with supranuclear gaze palsy, cherry red spot, BIG hepatosplenomegaly

Answer 15

Niemann-Pick = deficiency of sphingomyelinase

Question 16

Infant with profound weakness and HOCM or Adult with proximal muscle weakness and sleep apnea

Answer 16

Pompe disease = deficiency of alpha glucosidase (enzyme replacement therapy)

Question 17

child with hoarse voice, frequent URIs, hepatosplenomegaly, some learning problems; NO corneal clouding

Answer 17

Hunter disease = iduronate sulfatase deficiency. (enzyme replacement therapy) X-linked recessive

Question 18

child with coarse facies, hepatosplenomegaly, CORNEAL CLOUDING

Answer 18

Hurler disease = alpha iduronidase deficiency (enzyme replacement therapy)

Question 19

Muscle cramping after exercise, myoglobinuria (coffee colored urine after exercise)

Answer 19

McArdle disease = glycogen phosphorylase deficiency

Question 20

Skin LSD manifestations

Answer 20

coarseness

Question 21

Classic Gaucher cell appearance on histology

Answer 21

“crumpled tissue paper” appearance of cytoplasm (due to elongated lysosomes filled with glucocerebroside)