Single Gene Disorders Flashcards
What are inborn errors of metabolism?
Group of genetic disorders caused due to a deficiency of an enzyme required for the formation of a protein
Explain how an inborn error of metabolism occurs
Block at some point in the normal metabolic pathway
Mutation
Specific Protein
Transport Vesicle, Receptor, Membrane Pump, Structural element, Enzyme
What is a genetic disorder?
A disease that is caused by a change, mutation in an individual’s DNA sequence
What can cause a mutation?
Radiation
Chemicals
Infectious agents (HPV, Helicobacter pylori)
What is the effect of mutations on the population?
Increases biodiversity
What are silent mutations?
Change in a nucleotide but no change in amino acid sequence of polypeptide
What is a missense mutation?
Change in nucleotide which causes a slight change, slight different amino acid sequence
What causes sickle cell?
Point mutation
What is a nonsense mutation?
Nucleotide substituted and polypeptide synthesis causes the formation of premature stop codon.
What causes thalassemia?
Frame shift mutation, addition
What are disorders of amino acid metabolism?
PKU, Maple syrup urine disease, albinism
What are disorders of carbohydrate metabolism?
Galactosemia, Glycogen storage disease, lactose intolerance
What are disorders of protein metabolism?
Immunoglobulin deficiencies
Absent clotting factor: haemophilia
Alpha - 1 antitrypsin deficiency
What could suggest an inborn error of metabolism? (History)
Consanguinity
Jaundice
Seizures
Abdominal distension
Developmental delay
What could suggest an inborn error of metabolism? (Clinically)
Critically ill newborn
Organomegaly
Cataract
Dysmorphic features
Mental retardation
What causes PKU?
Increase of phenylalanine in the blood
What foods is phenylalanine found in?
Chicken, fish, milk, cheese and artificial sweeteners
What does a person with PKU have?
A mutation in the PAH gene chromosome 12
Signs and symptoms of PKU?
Intellectual disability,
Seizures,
Delayed development,
Behavioural issues,
Musty door of urine,
Light skin, blue eyes
Why do PKU patients often have light skin and blue eyes?
Obstruction in phenylalanine transforming to melanin
What causes maternal PKU?
High phenylalanine levels due to lack of diet restrictions
What happens if PKU reaches the fetus?
Low birth weight
Microcephaly
Heart defects
Increased risk of pregnancy loss
What is the treatment for PKU?
Diet for life, extremely low levels of phenylalanine
What is galactosemia?
Inherited condition associated with diminished ability to metabolise galactose
What causes galactosemia?
Deficiency of enzyme, galactose-1-phosphate uridylyltransferase
What are the three types of galactosemia?
Mutation in GALT gene, classic galactosemia
Galactosemia type II, mutation in GALK gene
Mutation is GALE gene, galactosemia type III
What are the early symptoms of galactosemia?
Jaundice
Vomiting
Poor weight gain
Hypoglycaemia
Feeding difficulties
Lethargy
What are the later symptoms of galactosemia?
Cataract
Intellectual disability
Liver failure
Kidney problems
Swelling
What are long term complications of galactosemia?
Poor growth
Learning disabilities
Fine & gross motor delays
Ovarian failute
Decreased bone density
What is the treatment for galactosemia?
Dietary restrictions
What cause lactose intolerance?
Reduced production of lactase
What is GSDI or Von Gierke disease?
Buildup of a complex sugar glycogen in body cells
What causes GSDI?
Deficiency in glucose-6-phosphatase
What are some signs of GSDI?
Babies sleep through night
Do not eat as frequently
Hypoglycaemia
Seizures
Lactic acidosis
Hyperuricemia
Hyperlipidemia
What is the treatment for GSDI?
Foods high in glucose
What tests should be given to babies with suspected IBM?
Blood count
Blood gases and electrolytes
Blood glucose
Plasma ammonia
Arterial blood lactate
Liver function
Urine ketones
Urine reducing substances
Serum uric acid
Which test is the standard test for diagnosis of PKU?
Urine reducing substances
What is in vivo?
Direct delivery of genes into the cells of a particular tissue in the body
What is ex vivo?
Transfer of genes to cultured cells and reinsertion
What is usually engineered to deliver the gene?
A vector, usually virus
Why is the vector modified prior to delivery?
Will not be able to cause disease when used in people
What are some types of viruses used as vectors?
Retroviruses
Adenoviruses
