MGD Clinical Conditions

Question 1

Amyloidosis

Answer 1

Misfolding of proteins leading to insoluble form of usually soluble protein
Effects depend on location (brain = Alzheimer’s/dementia)

Question 2

Sickle cell anaemia

Answer 2

Autosomal recessive
A -> T / Glu -> Val / hydrophilic -> hydrophobic
Creates hydrophobic knob which joins with hydrophobic pocket in beta chains when Hb is in T state
Polymerised Hb causes cell to adopt sickled shape
Blocks microvasculae and cause sickle crisis (lots of pain, downstream ischaemia)
Crisis precipitated by - smoking, obesity, cold, infection (reduce O2 availability and promote T state)
Haemolytic anaemia - result of spleen removing sickled RBCs
Jaundice - result of excess bilirubin from excess breakdown
Can have trait - mainly no symptoms but protection against malaria

Question 3

Cystic fibrosis

Answer 3

Autosomal recessive
Defective CFTR gene (most common one codon deletion)
Leads to impaired transport of Na+/Cl-
Osmosis causes thick mucus across body
Ciliary escalator no longer works, bacteria aren’t cleared and infections occur
Mucus blocks pancreatic duct causing pancreatitis and stopping fat digestion
Causes vas deferens not to form/become blocked in males - infertility
No cure, treatment - prophylaxis for lung infections, lipase to digest fats, bypassing of vas deferens

Question 4

Alpha thalassaemia

Answer 4

Decreased or absent alpha chains in Hb
Appears before birth
Can’t form stable tetramers
Reduced Hb -> reduced O2 capacity -> usual symptoms of anaemia

Question 5

Beta thalassaemia

Answer 5

Decreased or absent beta chains in Hb
Appears after birth (foetal Hb = alpha and gamma chains)
Can’t form stable tetramers
Reduced Hb -> reduced O2 capacity -> usual symptoms of anaemia

Question 6

Haemophilia A

Answer 6

Recessive X linked
Reduced/no factor VIII production -> blood can’t clot as well (factor Xa production down 50%)
Treatment - recombinant factor VIII, avoid thrombolytics/blood thinners

Question 7

Scurvy

Answer 7

Vitamin C deficiency
Prolyl hydroxylase can’t convert proline -> hydroxyproline -> reduced H bonds, less cross links, weakened structure, wobbly collagen

Question 8

Down’s syndrome (trisomy 21)

Answer 8

Extra 21st chromosome due to meiotic division error or Robertsonian translocation
Characteristic facial features, impaired intelligence, heart defects, increase leukaemia prevalence, increased early onset Alzheimer’s
Can be screened during pregnancy

Question 9

Edward’s syndrome (trisomy 18)

Answer 9

Extra 18th chromosome due to meiotic division error or Robersonian translocation
‘Rocker bottom’ feet, overlapping fingers, small lower jaw
Live 1-2 weeks

Question 10

Patau’s syndrome (trisomy 13)

Answer 10

Can be due to meiotic division error or Robersonian translocation
Congenital heart defects, cleft lip
Median survival = 2.5 days

Question 11

Turner’s syndrome (monosomy X)

Answer 11

Occurs only in women
Single sex chromosome
Missing one copy of small autosomal region at start of sex chromosomes
Short stature, heart defects, mild learning difficulties, neck webbing, infertility

Question 12

Klinefelter’s syndrome (XXY)

Answer 12

Occurs in men
Extra X chromosome -> smaller testes -> reduced testosterone production -> lack of male sex characteristics at puberty
Hypogonadism, infertility, no coarse body hair, gynaecomastia (enlargement of male breasts)
Treat with testosterone (will not reverse infertility)