Genetic Disorders: Autosomal recessive and X-linked (includes Lysosomal storage dz)

Question 1

Fabry’s disease –> enzyme def and what builds up; inheritance pattern
(sphingolipidosis, along w/ Gauchers, Niemann pick, Tay-sach, krabes and metachromic leukodystrophy)

Answer 1

1. α-galactosidase A
2. ceramide trihexoside
3. X-linked recessive

Question 2

Symptoms of Fabry’s disease (5)

Answer 2

1. peripheral neuropathy hands/feet
2. g.i. pain (fat build up in vessels–> ischemia)
3. renal failure
4. HTN
5. cardiomyopathy

Question 3

Gaucher’s disease; enzyme def. and waht builds up

Answer 3

1. Glucocerebrosidase
2. Glucocerebroside
3. AR (most common of lysosomal storage dz)

Question 4

Symptoms of Gaucher’s (2)

Answer 4

1. Hepatosplenomegaly–> lead to anemia and thrombocytopenia

2. bone crises (including aseptic necrosis of bone)

Question 5

microscopic fining in Gaucher’s

Answer 5

Macrophages swollen with blue cytoplasmic debris (fibrils)–> look like “tissue paper”, light blue staining

Question 6

Niemann-Pick disease–> enzyme def. and accumulation

Answer 6

1. sphingomyelinase
2. sphingomyelin

*is AR

Question 7

symptoms/ finding of Niemann-Pick (4)

Answer 7

1. neurodegen (ataxia, dysarthri, dysphagia; affects cerebellum)
2. hepatosplenomegaly
3. cherry-red spot on macula
4. foam cells

Question 8

Tay-Sach’s disease–> enzyme def. and accumulation

Answer 8

1. hexosaminidase A
2. GM2 ganglioside

*AR

Question 9

symptoms/ findings of Tay-Sach’s

Answer 9

1. progressive neurodegeneration and developmental delay
2. cherry-red spot on macula
3. NO HEPATOSPLENOMEGALY (dist. from Niemann-pick)
4. lysosomes w/ onion skin

Question 10

Krabbe’s dz–> enzyme def. and accumulation

Answer 10

1. Galactocerebrosidase
2. Galactocerebroside

*AR

Question 11

symptoms/ finding of Krabbe’s dz

Answer 11

1. Peripheral neuropathy
2. developmental delay
3. optic atrophy
4. globoid cells
   (muscle wasting, progressive weakness, vision loss, dementia); is a demyelinating dz
   *pt. usually dead by age 2

Question 12

Metachromic leukodystrophy enzyme def. and accumulation

Answer 12

1. Arylsulfatase A
2. Cerebroside sulfate

*AR

Question 13

symptoms of Metachromic leukodystrophy

Answer 13

similar to Krabbe’s–> muscle wasting, weakness, vision loss, dementia; but prob more central involvment (demyelination) like ataxia

Question 14

Huler’s syndrome–> enyme def. and acuumulation

Answer 14

1. α-L- iduronidase
2. heparan sulfate, dermatan sulfate

*AR; is a mucopolysaccharidosis

Question 15

symptoms of Hurler’s dz (5)

Answer 15

1. developmental delay
2. gargoylism (short stature, coarse facies)
3. Corneal clouding
4. hepatosplenomegaly
5. airway obstruction

Question 16

Hunter’s syndrome–> enzyme def. and acumulation; inheritance

Answer 16

1. Iduronate sulfatase
2. Heparan sulfate, dermatan sulfate

*x-linked recessive

Question 17

Main way to tell Hunter’s from hurlers, since presentation is otherwise same

Answer 17

Hunter’s has NO corneal clouding and is X-linked recessive

“Hunters see clearly and aim for the X”

Question 18

mutated gene in cystic fibrosis, what chromosome

Answer 18

CFTR 1 gene, chromosome 7

Question 19

6 symptoms of CF

Answer 19

1. recurrent pulmonary infections
2. chronic bronchitis
3. bronchiectasis
4. pancreatic insufficiency (failure to thrive)
5. Meconium ileus in newborn
6. nasal polyps

Question 20

what two agents are responsible for recurrent bacterial infection in CF pts

Answer 20

1. Pseudomonas

2. S. aureus

Question 21

what causes some CF infants to present with failure to thrive

Answer 21

fat soluble vitamin deficiencies due to malabsorption form pancreatic insufficiency

Question 22

issue males with CF have

Answer 22

infertility–> bilateral absence of vas deferens

Question 23

Tx for CF?`

Answer 23

N-acetylcysteine (breaks up mucous by cleaving disulfide bonds

Question 24

what Abx given for CF bacterial infections

Answer 24

fluoroquinolones

Question 25

10 X-linked recessive disorders

“Oblivious Female Will Give Her Boys x-Linked Disorders”
- one has two dz

Answer 25

1. Ocular albinism/ Ornithine Transcarbmoylase
2. Fabry’s dz.
3. Wiskott-Aldrich syndrome
4. G6PD deficiency
5. Hemophilia A and B
6. Bruton’s agammaglobulinemia
7. Hunter;s syndrome
8. Lesch-Nyhan syndrome
9. Duchenne (and Beckers) Muscular dystrophy