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

Question 1

Most common lethal disease in Caucasian population

Answer 1

Cystic fibrosis

Question 2

Cystic fibrosis inheritance mode

Answer 2

AR

Question 2

CFTR function

Answer 2

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

Question 3

Cystic fibrosis defect and mutation

Answer 3

CFTR gene on ch 7

Deletion of phe508 / AR

Question 4

Cystic fibrosis pathophysiology

Answer 4

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

Question 5

CL- concentration in sweat in cystic fibrosis

Answer 5

> 60meq/L

Question 7

Diagnosis of cystic fibrosis

Answer 7

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)

Question 8

Cystic fibrosis treatment

Answer 8

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

Question 8

N-acetylcysteine mechanism of action

Answer 8

Loosens mucus plugs (cleaves disulfide bonds within mucus glycoprotein)

Question 9

Cystic fibrosis complications

Answer 9

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

Question 10

Dormase alfa

Answer 10

DNAase to clear leukocyte debris

Question 11

CFTR ch

Answer 11

7

Question 12

Albinism mode of inheritance

Answer 12

AR

Question 13

Infantile polycystic kidney disease (ARPKD) mode of inheritance

Answer 13

AR

Question 14

Cystic fibrosis mode of inheritance

Answer 14

AR

Question 15

Glycogen storage disease modes of inheritance

Answer 15

AR

Question 16

Hemochromatosis mode of inheritance

Answer 16

AR

Question 17

Kartagener mode of inheritance

Answer 17

AR

Question 18

All mucolysaccharides are AR EXCEPT

Answer 18

Hunter syndrome

Question 19

Phenylketonuria mode of inheritance

Answer 19

AR

Question 20

Sickle cell anemia mode of inheritance

Answer 20

AR

Question 21

Thalassemias mode of inheritance

Answer 21

AR

Question 22

Wilson disease mode of inheritance

Answer 22

AR

Question 23

All shingolipidoses are AR except

Answer 23

Fabry disease

Question 24

Briton agammaglobulinemia mode of inheritance

Answer 24

XR

Question 25

Wiskott-Aldrich syndrome mode of inheritance

Answer 25

XR

Question 26

Fabry disease mode of inheritance

Answer 26

XR

Question 27

Ocular albinism mode of inheritance

Answer 27

XR

Question 28

Lesch-Nyhan mode of inheritance

Answer 28

XR

Question 29

Duchenne and becker mascular dystrophy mode of inheritance

Answer 29

XR

Question 30

Hunter syndrome mode of inheritance

Answer 30

HR

Question 31

Hemophilia A and B mode of inheritance

Answer 31

XR

Question 32

Ornithine transcarbamylase deficiency mode of inheritance

Answer 32

XR

Question 33

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

Answer 33

``` Dystrophin gene (DMD) Increased chance of spontaneous mutation ```

Question 34

DMD

Answer 34

Dystrophin gene

Question 35

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

Answer 35

``` Dystrophin gene (DMD) Increased chance of spontaneous mutation XR ```

Question 36

Dystrophin/primary tissue of action

Answer 36

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

Question 37

Dystrophin function

Answer 37

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

Question 38

Duchenne type of mutation

Answer 38

X-linked frameshift mutation

Question 40

Duchenne pathophysiology

Answer 40

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

Question 40

Gower maneuver

Answer 40

Patients use upper extremity to help them stand up

Question 41

Duchenne clinical manifestations

Answer 41

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

Question 42

Duchenne age of onset

Answer 42

Before 5

Question 43

Most common cause of death in Duchene

Answer 43

Dilated cardiomyopathy

Question 44

Becker dystrophy mutation

Answer 44

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

Question 45

Becker age of onset

Answer 45

Adolescence or early adulthood

Question 46

Duchenne vs becker dystrophy

Answer 46

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

Question 47

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

Answer 47

Myonecrosis | Both duchenne and Becker

Question 49

Duchenne diagnosis

Answer 49

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

Question 49

Myotonic type 1 muscular dystrophy gene

Answer 49

DMPK

Question 50

Myotonic type 1 muscular dystrophies pathophysiology

Answer 50

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

Question 51

Myotonic type 1 muscular dystrophy symtoms

Answer 51

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

Question 52

G6PD mode of inheritance

Answer 52

XR

Question 53

Fragile X syndrome major gene

Answer 53

FMR1 gene

Question 54

Fragile X pathophysiology

Answer 54

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

Question 55

Most common cause of genetic intellectual disability

Answer 55

Down syndrome

Question 56

Second most common cause of genetic intellectual disability

Answer 56

Fragile syndrome

Question 57

Trinucleotide repeat disorder of fragile x syndrome

Answer 57

CGG

Question 58

Fragile X syndrome findings

Answer 58

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

Question 59

Trinucleotide repeat expansion diseases feature

Answer 59

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

Question 60

Trinucleotide repeat expansion diseases

Answer 60

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

Question 61

Trinucleotide repeat expansion diseases

Answer 61

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

Question 62

Friedreich ataxia trinucleotide

Answer 62

GAA

Question 63

Huntington disease trinucleotide

Answer 63

CAG

Question 65

Myotonic dystrophy trinucleotide

Answer 65

CTG

Question 66

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

Answer 66

Pseudomonas in adolescence | S. aureus in early infancy

Question 67

Duchenne gait

Answer 67

Waddling gait

Question 68

Trinucleotide repeat expansion diseases

Answer 68

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