Single Gene Disorders Flashcards
When does Huntington’s usually appear?
30s or 40s
Symptoms of Huntington’s
Involuntary movements (worsen) called chorea, trouble walking, speaking, swallowing, thinking
Live about 20 years after symptoms begin
What is mechanism of Huntington’s?
Altered HTT gene is passed from one generation to next, causing CAG trinucleotide repeat to increase in size
Larger number of repeats = earlier onset of signs (anticipation)
What is familial hypercholesterolaemia (FH)?
Disorder of cholesterol metabolism, resulting in cholesterol deposited within macrophages in specific sites
Most common inherited metabolic disease
What does FH lead to?
Premature atherosclerosis, CVD, death
Cause of FH?
Autosomal dominant mutations in LDLR (low density lipoprotein receotor) causing it to be absent or defective
Symptoms of FH?
- Xanthelasma - Cholesterol deposits in eyelid
- Arcus corneas - Cholesterol infiltration around corneal rim due to deposition of lipids. No consequences to vision.
- Tendinous Xanthomas - Deposits within tendons (hands, feet, elbows, knees)
- Xanthomas - Bumps due to high levels of lipids in blood
Treatment of FH?
High levels of cholesterol-lowering drugs
What type of disease is cystic fibrosis?
Autosomal recessive inheritance - must be homozygous recessive to be affected (2 copies of mutated gene)
What type of disease is Duchenne Muscular Dystrophy?
X-linked recessive
What is Duchenne Muscular Dystrophy?
Difficult to stand up - weak proximal muscles due to absence of dystrophin
What is Phenylketonuria (PKU)?
An inherited inability to metabolise phenylalanine, which, if untreated, causes brain and nerve damage
Most prevalent inherited defect in amino acid metabolism
1 in 10,000 live births
How is PKU inherited?
Autosomal recessive pattern - person has 2 copies of altered gene
What is phenylalanine?
An essential amino acid that isn’t synthesised in the body
What is concentration of phenylalanine in the blood determined by?
Dietary intake
Balance between protein synthesis and catabolism
What enzyme is deficient in PKU?
Phenylalanine hydroxylase
What is treatment for PKU?
Dietary restriction of natural phenylalanine intake from protein
Enzyme replacement - treatment with ‘PEGylated’ enzyme to substitute for deficient phenylalanine hydroxylase –> PAL which reduces blood phenylalanine levels
What is alkaptonuria (AKU)?
A rare disorder of autosomal recessive inheritance caused by a mutation in a gene that results in the accumulation of homogentisic acid (HGA)
What does excess HGA result in?
Dark urine which turns black upon standing (present from birth)
