Cystic Fibrosis, other AR diseases, mascular dystrophies and other X link disorder Flashcards Preview

Biochemistry FA > Cystic Fibrosis, other AR diseases, mascular dystrophies and other X link disorder > Flashcards

Flashcards in Cystic Fibrosis, other AR diseases, mascular dystrophies and other X link disorder Deck (68):
1

Most common lethal disease in Caucasian population

Cystic fibrosis

2

Cystic fibrosis inheritance mode

AR

2

CFTR function

Encodes an ATP gated CL- channel that secretes CL- in lungs and GI tracts and reabsorbs CL- in sweat glands

3

Cystic fibrosis defect and mutation

CFTR gene on ch 7
Deletion of phe508 / AR

4

Cystic fibrosis pathophysiology

Misfolded protein accumulates in RER-->decreased CL- and (water) secretions--> increased sodium and water reabsorption via epithelial sodium channels--> THICK MUCUS SECRETIONS INTO LUNGS AND GI. Also more negative transepithelial potential negative

5

CL- concentration in sweat in cystic fibrosis

>60meq/L

7

Diagnosis of cystic fibrosis

1. CL> 60 meq/L in sweat
2. Contraction alkalosis and hypokalemia (Na/water losses and concomitant renal K+/H+ wasting) --> just like LOOP DIURETICS
3. increased immunoreactive trypsinogen (newborn screening)

8

Cystic fibrosis treatment

1. N-acetylcysteine
2. Dornase alfa (aerolized)
3. pancreatic enzymes for insuficiency
4. Azithromycn (as anti-inflammatory agent)
5. chest physiotherapy
6. albuterol

8

N-acetylcysteine mechanism of action

Loosens mucus plugs (cleaves disulfide bonds within mucus glycoprotein)

9

Cystic fibrosis complications

1. Recurrent pulmonary infections (Pseudomonas in adolescence, S. aureus in early infancy )
2. Chronic bronchitis and bronchiectasias (reticulonobular pattern on CXR)
3. Pancreatic insufficiency, malabsorption and steatorrhea
4. NASAL POLYPS
5. Meconium ileus in newborn
6. Infertility in males (absence of vas deferens, absent sperm spermatogenesis may be unaffected)
7. Clubbing nails
8. Subinfertility in females (amenorrhea, abnormally thick cervical mucus
9. biliary cirrhosis
10 liver disease

10

Dormase alfa

DNAase to clear leukocyte debris

11

CFTR ch

7

12

Albinism mode of inheritance

AR

13

Infantile polycystic kidney disease (ARPKD) mode of inheritance

AR

14

Cystic fibrosis mode of inheritance

AR

15

Glycogen storage disease modes of inheritance

AR

16

Hemochromatosis mode of inheritance

AR

17

Kartagener mode of inheritance

AR

18

All mucolysaccharides are AR EXCEPT

Hunter syndrome

19

Phenylketonuria mode of inheritance

AR

20

Sickle cell anemia mode of inheritance

AR

21

Thalassemias mode of inheritance

AR

22

Wilson disease mode of inheritance

AR

23

All shingolipidoses are AR except

Fabry disease

24

Briton agammaglobulinemia mode of inheritance

XR

25

Wiskott-Aldrich syndrome mode of inheritance

XR

26

Fabry disease mode of inheritance

XR

27

Ocular albinism mode of inheritance

XR

28

Lesch-Nyhan mode of inheritance

XR

29

Duchenne and becker mascular dystrophy mode of inheritance

XR

30

Hunter syndrome mode of inheritance

HR

31

Hemophilia A and B mode of inheritance

XR

32

Ornithine transcarbamylase deficiency mode of inheritance

XR

33

Which gene has the largest coding region of any human gene
Clinical correlation

Dystrophin gene (DMD)
Increased chance of spontaneous mutation

34

DMD

Dystrophin gene

35

Which gene has the largest coding region of any human gene
Clinical correlation / mode of inheritance

Dystrophin gene (DMD)
Increased chance of spontaneous mutation
XR

36

Dystrophin/primary tissue of action

It helps anchor muscle fibers, primary in skeletal and caridac muscle

37

Dystrophin function

Anchor muscle fibers
Connects intracellular cytoskeleton (actin) to the transmembrane proteins α and β dystroglycan , which are connected to extracellular matrix

38

Duchenne type of mutation

X-linked frameshift mutation

40

Duchenne pathophysiology

X-linked frameshift mutation--> truncated dystrophin protein -->accelerated muscle breakdown and inhibited muscle regeneration

40

Gower maneuver

Patients use upper extremity to help them stand up

41

Duchenne clinical manifestations

1. Weakness begins in pelvic gridle muscles and progress superiorly
2. Pseudohypertrophy of calf muscle (fibrofatty replacement of muscle
3. Gower maneuver
4. Dilated cardiomyopathy
5. Waddling gait

42

Duchenne age of onset

Before 5

43

Most common cause of death in Duchene

Dilated cardiomyopathy

44

Becker dystrophy mutation

X-linked point mutation in dystrophyn gene (no frameshift)

45

Becker age of onset

Adolescence or early adulthood

46

Duchenne vs becker dystrophy

Becker is less severe
Becker has point mutation
Becker onset in adolescence or early adulthood (duchenne before 5)

47

Loss of dystrophin results in......
It can cause ...

Myonecrosis
Both duchenne and Becker

49

Duchenne diagnosis

1. high CK and aldolase
2. Western blot
3. biopsy to confirm

49

Myotonic type 1 muscular dystrophy gene

DMPK

50

Myotonic type 1 muscular dystrophies pathophysiology

AD --> CTG repeat expansion in the DMPK gene---> abnormal expression of myotonin protein kinase

51

Myotonic type 1 muscular dystrophy symtoms

1. Myotonia 2. Muscle wasting 3. Frontal balding 4. Cataracts 5. Testicular atrophy 6. Arrythmia

52

G6PD mode of inheritance

XR

53

Fragile X syndrome major gene

FMR1 gene

54

Fragile X pathophysiology

X-linked defect affecting methylation and expression of FMR1 gene
Trinucleotide repeat disorder CGG

55

Most common cause of genetic intellectual disability

Down syndrome

56

Second most common cause of genetic intellectual disability

Fragile syndrome

57

Trinucleotide repeat disorder of fragile x syndrome

CGG

58

Fragile X syndrome findings

1. Post pubertal macroorchidism (enlarged testes)
2. Long face with large jaw
3. Large everted ears
4. Autism
5. Mitral valve prolapse

59

Trinucleotide repeat expansion diseases feature

Anticipation: increased severity and decreased age of onset in successive generation

60

Trinucleotide repeat expansion diseases

1. Fragile x syndrome - CGG
2. Friedreich ataxia - GAA
3. Huntington - CAG
4. Myotonic Dystrophy - CTG

61

Trinucleotide repeat expansion diseases

1. Fragile x syndrome - CGG
2. Friedreich ataxia - GAA
3. Huntington - CAG
4. Myotonic Dystrophy - CTG

62

Friedreich ataxia trinucleotide

GAA

63

Huntington disease trinucleotide

CAG

65

Myotonic dystrophy trinucleotide

CTG

66

Recurrent pulmonary infections in CF - bugs(Pseudomonas in adolescence, S. aureus in early infancy )

Pseudomonas in adolescence
S. aureus in early infancy

67

Duchenne gait

Waddling gait

68

Trinucleotide repeat expansion diseases

1. Fragile x syndrome - CGG
2. Friedreich ataxia - GAA
3. Huntington - CAG
4. Myotonic Dystrophy - CTG