genetic conditions

Question 1

HHC - haemochromatosis

Answer 1

iron overload, 20-60 g normal is usually 4
organ dysfunction:
- liver cirrhosis
- pancreas bronze diabetes
- skin bronze or grey
-heart restrictive CM
-pituitary - hypogonadism, impotence
-joints - arthralgia (especially hands), chondrocalcinosis

usually AR
** haemosiderosis is the secondary condition and haemochromatosis is the genetic condition
DX by checking serum ferritin level (indicator for iron overload) also the transferrin saturation.
tx: weekly venesection 500ml until serum ferritin is <100mcg/L and serum transferrin saturation <50% and iron levels normal
** desferrioxamine can be used but not as effective as venesection
keep normal diet, avoid or limit alcohol, life expectancy should be normal is treated before cirrhosis or diabetes develop.

Question 2

Dxt of thalassaemia

Answer 2

pallor + jaundice + hepatosplenomegaly

Question 3

Diagnosis of Thalassaemia

Answer 3

FBE: mean cropuscular Hg/ mean corpuscular volume is low but can be normal
Hg electrophoresed: measure adult Hg HbA and other variants
serum fereritin level: to distinguish b/w iron def
DNA analysis

Question 4

clx features of thalassaemia

Answer 4

carriers are clinically asx, pts, w/ major have severe anaemia, children can be lethargic and inactive, failure to thrive or to grow and delayed puberty, hepatosplenomegaly and jaundice
*signs usually appear after 6 months and death from cardiac failure used to be common but regular blood transfusions and iron chelating treatment are used

Question 5

tx of thalassaemia

Answer 5

regular blood transfusion for the anemia
avoid iron supplementation
folate supps and a low iron diet are recommended
excess iron can be removed w/ iron chelators : deferrioxamine
allogenic bone marrow transplantation has been used with success
splenectomy may be appropriate

Question 6

Dxt of cycstic fibrosis

Answer 6

failure to thrive + chronic cough + loose bowel actions

Question 7

CF

• defect
• genetic profile

Answer 7

• defect in ion channel protein, transmembrane receptor (in cells lining the exocrine ducts) affecting normal tp of cloride ions leading to dec sodium and water transfer causing viscid secretions affecting lungs, pancreas, and gut
• most common AR in peds, 1 in 2500 caucasian aff. 1 in 20-25 are carriers, mutation in delta-F508 of chromosome 7

Question 8

clx features of CF

Answer 8

• general: malaise, failure to thrive, exercise intolerance
• chronic resp probs: cough recurrent pneumonia, sinus tenderness, nasal polyps
• G.I: malabs, pale loose bulky stool, jaundice, meconium ileus (10% of newborns)
• infertility in males (Vas def)
• panc insuff
• early mortality but improving survival rates (mean age is 31 now)

Question 9

tx of CF

Answer 9

no current cure,

• early dx and multidisciplinary team care
• physiotherapy for drainage of airway secretions
• hypertonic saline solution by nebuliser preceded by a bronchodilator
• tx for infections: therapeutic and prophylactic AB
• oral panc EZ replacement
• dietary manipulation
• lung and liver TP are considerations

Question 10

dxt of NF1

Answer 10

light brown skin patches + skin tumors + axillary freckles

Question 11

clx features of NF1

and general rule

Answer 11

• 6 or more cafe-au-lait spots(increasing w/ age)
• freckling in axillary or inguinal regions
• flesh coloured cutaneous tumors (appears at puberty)
• Htn
• eye features (iris hamartomas)
• learning difficulties
• musculoskeletal problems
• optic nerve gliomas
• ** general rule 1/3 asx, 1/3 w/ minor probs mainly cosmetic, 1/3 w/ sig probs

Question 12

Dxt of DMD

Answer 12

male child + gait +bulky calves

Question 13

clx features of Duchenne muscular dystrophy (DMD)

Answer 13

• XR, mutation in the dystrophin gene (protein found inside the muscle cell membrane)
• usually dx from 2-5 years, weakness in hip and shoulder girdles
• walking probs, can be delayed onset starting in boys aged 3-7
• waddling gait, falls, difficulty standing and climbing stairs
• pseudohypertropy of muscles esp calves
• intellectual retardation
• most die of resp. probs by the age of 25
• *** Gower sign: uses hands to climb up his or her legs when rising an erect position

Question 14

dx of DMD and tx`

Answer 14

dx: elevated serum CK, electromyography, direct dystrophin gene testing, muscle biopsy
- tx: counseling, esp genetic counseling, education and screening esp mothers,
* **no specific treatment available, support, corticosteroid delay progression

Question 15

Dxt of huntingon disease

Answer 15

chorea + abnormal behaviour + dementia + family history