Genetics and Health Week 5

Question 1

Phenylketonuria

A) Definition 
B) Mutation in what gene? 
C) Type of Disorder
D) Symptoms 
E) Additional Phenotypes 
F) Treatment 
G) Management

Answer 1

A) A metabolic disorder that is phenylalanine hydroxylase-deficient, leading a build-up of phenylalanine in the tissues

B) A missense mutation (p.Arg408Trp) in the PAH gene which codes for phenylalanine hydroxylase (converts Phe to Tyr)

C) Autosomal Recessive

D) 
	Vomiting 
	Irritability 
	An eczema-like rash 
	A mousy odor to the urine (Musty type of cell) 
	Increased muscle tone 
	More active muscle tendon reflexes 
	Sudden changes in the nervous system 
	Cognitive impairment
	Seizures 

E) 
	Microcephaly (small head) 
	Prominent cheek and upper jaw bones with widely spaced teeth 
	Poor development of tooth enamel 
	Decreased body growth

F)
 Screening for newborns for levels of ph
enylalanine
 Few drops of blood are obtained by a small prick on the hell, placed on a Guthrie card and then sent for measurement
 Performed before or soon after discharge from the hospital (for various common abnormalities

G)
 The blood level of phenylalanine must be maintained (2-10 mg/dL), if you managed your intake, you will not see the symptoms
 Not eliminated, just reduced
 Avoid high protein foods such as meat, fish, poultry, eggs, cheese, milk, dried beans and peas
 Increased intake of starch and carbohydrates
 However, there are mothers who cannot follow a low-phenylalanine diet during pregnancy, their babies have a high risk of intellectual disability before birth
 Maternal effect: the mother’s genetic disorder affects the child regardless of inheritance, it is more of an environmental change

Question 2

Explain the Concept of Compound Heterozygotes

Answer 2

An Individual that has two different alleles which are both defective
These two mutations might have a different outcome

Question 3

Define Thalassemia

Answer 3

Blood disorder that is passed down through families (inherited) in which the body makes an abnormal form or inadequate amount of hemoglobin

Question 4

What are the two types of thalassemia?

What genes are affected in each?

Answer 4

Alpha-thalaessmia (affects HBA1 or HBA2 genes)

• Need to manage our iron levels
• 4 types: 3 phenotypic manifestations

o Beta-thalaessmia (affects HBB gene)
- Major: Two damaged genes, severe version of beta thalassemia
- Intermedia: Two damaged genes, causes mild to moderate anaemia
Cured using bone marrow transplantation
- Minor: one damaged gene, lifelong mild anaemia

Question 5

Define Sickle Cell Anaemia

Answer 5

Affects the HBB but leads to a different outcome
It has a single amino acid substitution causing fibre formation
alters the structure of our red blood cells

Question 6

Haemochromatosis

Definition
Mutation in which gene
Treatment
Symptoms

Answer 6

o Inherited disorder that causes the body Absorb too much iron from the person’s diet
o Extra iron build-up damages the organs, causing them to fail
o The iron can become part of the haemoglobin
o The extra iron is stored in the liver, heart and pancreas
o Caused by mutations in the HFE gene, doesn’t bind to the transferrin receptor
o Also mutations in the HAMP, HFE, HFE2, SLC40A1, or TFR2 genes
o Missense Mutations: Cys282Tyr (Cysteine to Tyrosine) (Most common) and His63Asp (Histidine to Aspartic Acid)
o Screened for iron content in the blood and in the liver

Symptoms
 Fatigue, lack of energy, joint pain, abdominal pain, loss of sex drive and heart problems
 They occur in men between the ages of 30 and 50
 They occur in women over the age of 50 due to Menstruation and that regular bleeding is the treatment for this disease
 Many people show few symptoms before irreversible organ damage commences

Question 7

Cystic Fibrosis

Defintion
Affects which organ systems
Mutation in which gene
Medications and Treatment

Answer 7

o Inherited disorder that causes severe damage to the lungs, digestive system and other organs in the body
o It is a recessive genetic condition that affects Australian children
o Caused by mutations in the CFTR (Cystic Fibrosis transmembrane regulator), disrupts the function of chloride channels systemically)
o Most common cystic fibrosis mutation consists of a deletion
o Chloride draws water in, causes the build-up of mucus, cilla cannot move
o Susceptible to infections of the lungs as the mucus builds up
o The pancreas is unable to secrete it’s digestive enzymes through the gland
o The intestine does not receive the digestive enzymes, resulting in lots of fats in the stool sample
o Can cause blockage in the vas deferens, leading to infertility
o In the sweat glands, the salt is not taken back by the body, affecting the process of cooling down
o P.Phe508del is the common mutation (3 base pair deletion)
o W1282X (Trp1282), G542X (Gly542) Nonsense Mutations
o G551D (Gly551Asp) and N1303K (Asn1303Lys) Missense Mutations
o Still discovering more mutations that lead to Cystic Fibrosis
o Patients with Cystic fibrosis have a difficult lifestyle, they have session with one or two nebulizers and bronchodilators every morning, every night with physio sessions in between, intake of 40 tablets per day that consist of pancreatic enzymes every time they eat, need to maintain their nutrition, exercise as much to keep their lungs moving throughout the day and even take psychological counselling as it can be very stressful
o Antibiotic resistance is a concern particularly for this disorder
o There can be a build-up of bacteria and if it reaches the peak level (danger zone), it can be hard for individual to return

Treatments
 Screening Tests (for the general population)
- Guthrie Card/ ultrasound

 Diagnostic tests (done at a individual level)

• Amniocentesis, buccal swab for sequencing
• Still need the genome sequence

 Screening newborns by obtaining blood sample to check if there is higher levels of immunoreactive trpsinogen that is released from the pancreas (this doesn’t detect all cases of cystic fibrosis)

 Medications

• Antibiotics
• Mucus-thinning drugs: patients can cough up the mucus which improves lung function
• Bronchodilators: open the airways by relaxing the muscles around the bronchial tubes
• Oral pancreatic enzymes: help the digestive tract to absorb nutrients

 Chest physical therapy: break up that mucus in the chest
 Pulmonary rehabilitation: Exercise education program to teach people with lung disease to manage their breathlessness
 Organ Transplant: considered as a last resort, to extend and improve the quality of life
 Gene therapies are being developed, reintroduce a copy of the CTFR gene