Antenatal Screening for Metabolic and Genetic Disorders: Postnatal Diagnostic and Treatment Options

1. Antenatal – move the cards to complete the table

2. Antenatal Screening

3. Learning Outcomes • Explain how post natal screening for metabolic disorders and genetic disorders occurs • Identify potential treatment options including PGD

4. Postnatal Screening; Diagnostic for metabolic disorders Metabolic disorders, such as phenylketonuria (PKU – substitution missense on chromosme 12), are screened for shortly after birth. PKU tested by excess phenylalanine in first days of life. Other disorders include galactosaemia, congenital hypothrodism and amino acid disorders.

5. Postnatal Screening; Diagnostic for metabolic disorders Phenylketonuria (PKU) patients have a build up in phenylalanine in the blood and some of it is converted into phenylpyruvic acid. The excess of both these compounds disrupts the normal development of organs, including the brain. Children suffering from PKU are given a low phenylalanine diet.

6. PKU Metabolism ANSWER THESE; • Which enzyme is missing in a person with PKU? • What are the consequences of a build up of phenylpyruvic acid? • Why can people with PKU eat phenylalanine when they are grown up? • Why are people with PKU still able to produce melanin?

7. PKU Metabolism • Which enzyme is missing in a person with PKU? A • What are the consequences of a build up of phenylpyruvic acid? Brain/organ disruption • Why can people with PKU eat phenylalanine when they are grown up? Brain fully developed – so minimal adverse effects • Why are people with PKU still able to produce melanin? Alternative pathway, tyrosine another amino acid.

8. Genetic Screening and counselling Post natal genetic disorders can be either categorized as sex-linked or autosomal Sex Chromosomes - pair 23 , X or Y Autosomes – all other chromosomes A pattern of inheritance can be revealed through construction of a family tree (pedigree chart). Phenotypes are known and then genotypes calculated. Symbols;

9. Genetic Screening and counselling For each type of disease – use the information to work out each of the pedigree trees Symbols;

10. Autosomal recessive inheritance eg. Cystic Fibrosis • When recessive – usually; • Trait relatively rare • Trait may skip generations • Trait in some offspring (esp. If consanguineous (cousins) marriage • Males and females affected in equal number • When recessive can add in genotype (as must be homozygous recessive double cc) • Then can work out backwards – as one from each parent etc.

11. Autosomal recessive inheritance 2 1 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

12. Autosomal recessive inheritance 1 Cc Cc 2 3 4 5 6 7 8 cc 4 5 cc Cc Cc 9 10 11 12 13 14 Cc or CC cc cc 15 16 17 18 Cc Cc Cc Cc

13. Autosomal dominant inheritance eg Huntington’s Disease/Chorea • When recessive – usually; • Trait in every generation • Each suffer has affected parent • Branches of tree not express trait, trait fails to reappear in future • Males and females affected in equal number • All non-suffers must be homozygous recessive double hh • Then can work out backwards – as one from each parent etc.

14. Autosomal dominant inheritance 2 1 1 2 3 4 3 4 5 6 7 8 5 6 7 8 9 10 11 9 10 11 12 13 14 12 13 14 15 15 16 17 18

15. Autosomal dominant inheritance 2 1 1hh 2 Hh 3hh 4hh 3 4 5 6 7 8 5 Hh 6 hh 7 hh 8 hh 9 Hh 10 hh 11 hh 9 10 11 12 13 14 12 hh 13hh 14 Hh 15hh 15 16 17 18

16. Autosomal incomplete dominant inheritance eg Sickle cell anaemia • Usually; • Full expression rare • Partial expression more frequent • Full suffer has parents with partial • Males and females affected in equal number • All non-suffers must be homozygous for one incompletely dominant allele • Suffers are homozygous of other dominant allele • Partial must have one each • Then can work out backwards – as one from each parent etc.

17. Autosomal incomplete dominant inheritance 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

18. Autosomal incomplete dominant inheritance 1 HS 2 HS 3 4 5 6 7 8 9 HS HS HH HH HS SS HH 10 11 12 13 14 15 16 17 18 HH HH HS HH HH HS HS HH HH

19. Se inheritance eg Huntington’s Disease/Chorea • When recessive – usually; • Trait in every generation • Each suffer has affected parent • Branches of tree not express trait, trait fails to reappear in future • Males and females affected in equal number • All non-suffers must be homozygous recessive double hh • Then can work out backwards – as one from each parent etc.

20. Sex-linked recessive inheritance eg. Haemophilia • When sex-linked recessive – usually; • Many more males affected than females • None of sons of an affected male shows the trait • Some grandsons may have trait • shown as XhXh or XhYh • When recessive can add in genotype • Then can work out backwards – as one from each parent etc. All sex-linked genes

21. Sex-linked recessive inheritance 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

22. Sex-linked recessive inheritance 1 XHY 2 XHXh 3XHXh 4 XhY 5 XHY 6 7 8 9 10 11 12 13 XHXh XhY XHXh XHXh XHY XHY XHY XHY 14 15 16 17 18 XHXh XhY XhY XHXh XHXh

23. Sex-linked recessive inheritance 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

24. Screening; what are the benefits? If pedigree charts show a high chance – then could use IVF and PGD to select an unaffected embryo. Some ethical considerations??

25. This is just plain wrong! I can see how someone else would object Ethical Square Can’t Won’t Nothing wrong with that I can see how others will see the good in this

26. Is it the same to screen for Huntington’s diseases and for a predisposition for asthma?

27. Is it right to select embryos to ensure tissue matches for other members of the family?

28. Is it worse to discard embryo’s or have an abortion?

29. Demonstrate your understanding • By what means is postnatal screening for phenylketonia (PKU) carried out? • What is PKU described as an inborn error of metabolism? 3. What treatment is given to sufferers of PKU? 4. Name two characteristics of a family’s pedigree chart what would enable a geneticist to recognise that it showed a pattern of autosomal recessive inheritance. 5. Give one rule that the geneticist would apply when adding genotypes to a family tree showing a pattern of autosomal recessive inheritance?

30. Demonstrate your understanding • Name TWO characteristics of a family’s pedigree chart that would enable a geneticist to recognise that it showed a pattern of sec-linked recessive inheritance. • Give ONE rule that the geneticist would apply when adding genotypes to a family tree showing a pattern of sex-linked recessive inheritance.

31. Review – Go fix Glossary • Read the definition on your glossary sheet • Then choose a word from the list .....

32. Revise Complete what should you know – p156