Aims of this session
- Introduce clinical genetics as a medical discipline
- discuss the processes used to identify a genetic disorder
- present the roles of the people involved: family, GP, Clinical geneticist, laboratories
- To demonstrate facets of clinical Genetics practice - diagnostic, psyuchological, ethical
- De deliver an apprecation of how moleculat and clinical genetics are integrated
Challenges in genetic medicine today
For single gene disorders
- There are vast variety the aetiology of a single genetic disorder. this leads to Chromosomal disorder
- as molecular techniques are now being used massive heterogeneity are being found Diseases with complex aetiology
- we are struggling to find the complete genetic base and aetiolgy of these illnesses Cancer
- we are finding it difficult to use genetic sequencing to deploy precision medicine Drug design and response
- we do not completely yet have personalised genetic screening and specific treatments
Newborn screening
Old regime
we used to screen for a number of diseases but this number has grown this was done through heel prick test
The screened diseases were
- biotinidase deficiency
- congenital adrenal hyperplasia
- Cystic fibrosis
- galactosaemia
- hypothyroidism
- maple syrup urine disease
- phenylketonuria
New regime
complete mass spectroscopy of blood metabolites. It is a catchall test.
Case: Sudden Unexplained Death In Infants (SUDII)
no abnormalities other than fatty infiltration of the liver. (stoatosis of the liver) This leads to think of metabolic abnormalities
our mass spec screen shoed abnormal Acyl carnitine profile. Diagnosis: Medium Chain Acyl Dehydrogenase deficiency.
MCADD
This is a common enzymatic defect, where you cannot convert FFAs to Ketone bodies. This leads to an energy deficit and death.
1/20000 babies 25% present as sudden death under 2 yrs Episodes of vomiting and nonketotic hypoglycemia Many are non penetrant Minimal pathology post mortem. Unmetabolised FFas excreted as acyl carnitine conjugates in urine
NOTE
GENETIC counselling
The family will of course have questions like
- What killed my healthy child
- What causes it?
- Will it happen again to other family members
- Can we prevent it from happening
And we should rightfully strive to Answer these questions
Genetics of MCAD
Recurrence risk
Mutations detection
and so the families options are
Genetic counselling
The results
DNA diagnositcs
Whats next?