Lecture 6 - Inborn Errors of Metabolism Flashcards
What is an inborn error of metabolism (IEM)?
An inherited, genetic disorder involving disorders in metabolism, usually where the gene for an enzyme which is required for the conversion of something is defected
What were the three events that lead to newborn screening before Guthrie showed up?
- The concept of IEM (by Archibald Garrod)
- Discovery of PKU
- Discovery of a diet for PKU
What are some considerations for screening for diseases?
- The disease is at a high enough frequency in population
- It can be missed clinically at birth
- A delay in diagnosis = permanent damage
- A simple, reliable test exists
- A treatment or intervention exists if the disease is caught early
What are some potential problems for getting genetically tested?
Emotional, social, and financial consequences of the results. People may feel angry, guilty, etc. at their results
What is a validated test/assay?
Validation = correct result
The test can be depended on for the result that is obtained.
In regards to reliability of tests, what does “sensitivity” and “specificity” refer to?
Sensitivity is a characteristic where a positive test result is correct.
Specificity is when a negative result is truly negative
What is alkaptonuria?
A disorder of phenylalanine and tyrosine metabolism
What kinds of functions are disturbed in a metabolic disease?
At the small molecule level (eg. proteins, lipids, etc.) and at the organelle level (mitochondria, etc.)
What is a neonate?
An infant in the first 28 days of life
How do you recognize a metabolic disorder and what do you do about it?
Create an index of suspicion (IOS)
Simple laboratory tests (glucose, ketones, etc. in blood)
Essentially look for loss of homeostasis
What does an index of suspicion tell you?
A high IOS = high likeliness of having a disease
How do you generate an IOS?
Generate a family history Most IEMs are recessive Neonatal deaths, fetal losses Consanguinity, ethnicity MtDNA
How common are metabolic diseases?
As a group, not uncommon. However, specifically looking for one would be very rare
How are metabolic diseases treated?
Dietary restriction/supplementation, organ transplant, enzyme replacement therapy, gene therapy, and stimulate alternate pathway
What is an ACT sheet?
The ACT sheet describes the short-term actions a health professional should follow in communicating with the family and determining the appropriate steps in the followup of the infant who has screened positive.
