12 June 2023

 

12 June 2023.

 

31	Jenny Myers. Diabetes in pregnancy
32	EMQ. Phenylketonuria
33	EMQ. Hepatitis D
34	EMQ. Cervical cancer staging

 

Try to answer all the questions without preparation before the tutorial –  this helps facts stick in long-term memory. Use ‘intelligent guessing’ for those you have no clue about.

 

31.   Jenny Myers. Diabetes in pregnancy.

Jenny is Professor of Obstetrics & Maternal Medicine at the University of Manchester and a Consultant Obstetrician at St Mary’s Hospital, the main teaching hospital in Manchester. She is Lead for the Manchester Maternal Medicine Service and has special interest in diabetes and hypertension. She brings clarity to the latest, best practice. It is best if you join live as she is happy to deal with questions, but her talk will be available to download from Dropbox.

 

32.   EMQ. Phenylketonuria.

Abbreviations.

IUGR:       intrauterine growth retardation.

PA:           phenylalanine.

PAH:        phenylalanine hydroxylase.

PAHD:     phenylalanine hydroxylase deficiency.

PARD:      phenylalanine-restricted diet.

PKU:         phenylketonuria  .

PPP:         pregnancy prevention programme.

Option list.

A	autosomal dominant
B	autosomal recessive
C	X-linked dominant
D	X-linked recessive
E	1 in 100,000
F	1 in 50,000
G	1 in 10,000
H	1 in 5,000
I	deficiency in phenylalanine hydroxylase
J	deficiency in phenylalanine oxidase
K	deficiency in phenylalanine transferase
L	deficiency in phenylketone hydroxylase
M	deficiency in phenylketone oxidase
N	raised PA levels
O	reduced PA levels
P	raised tyrosine levels
Q	reduced tyrosine levels
R	normal tyrosine levels
S	No
T	Yes
U	unknown

Question 1.        What is PKU? Write your answer – there is no option list.

Question 2.        What is PKU due to? Use the option list.

Question 3.        What levels of PA and Tyr are typical in PKU? Use the option list. This is not a real EMQ

as there are two answers.

Question 4.        Is PKU subdivided into different categories? If “yes”, what are the categories? Write

your answer – there is no option list.

Question 5.        Which, if any, of the following statements are true about hyperphenylalaninaemia?

This is not a true EMQ as more than one answer may be correct.

Option List

A	it blocks growth hormone
B	it destroys astrocyte miosis
C	it disrupts folic acid activity
D	it enhances vitamin A activity
E	it interferes with myelin synthesis
F	it negates the effects of vitamin C
G	nobody knows, nobody cares; especially me

Question 6.        How is PKU inherited? Use the option list.

Question 7.        Which chromosome houses the gene related to PKU transmission?

Question 8.        How many mutations of the gene related to PKU have so far been identified?

Question 9.        Is a person with PKU likely to have one or two mutations of the PKU gene?

Question 10.    What is BH4?

Question 11.    What is pegvaliase?

Question 12.    What is the approximate prevalence of PKU in Caucasians?

Question 13.    What is the approximate prevalence of PKU carrier status in Caucasians?

Question 14.          The prevalence of PKU varies between ethnic groups. Match each of the following ethnic groups to the closest prevalence given in the option list.

Question 15.    Which, if any, of the following are characteristic of PKU?

Option list.

A	alopecia
B	angst
C	facial dysmorphism
D	facial hair in females and pre-pubertal males
E	kyphosis
F	macroorchidism in post-pubertal males

Question 16.    Are fetal PA levels higher or lower than maternal?

Question 17.    Which, if any, of the following  are true in relation to the maternal PKU syndrome?

This is not a true EMQ as there may be more than correct answer.

Option list.

A	asymptomatic bacteruria is more common
B	cholestasis of pregnancy is more common
C	early onset gestational hypertension is more common
D	eczema is more common
E	gallstones are more common
F	miscarriage is more common
G	MPKUS is usually due to non-adherence to a low phenylalanine diet
H	porphyria is more common
I	reversible posterior cerebral syndrome is more common
J	urinary tract urea stones are more common
K	none of the above

Question 18.    What are the main consequences for the offspring of untreated maternal PKU?

Question 19.    Is neonatal screening for PKU routine in the UK?

Question 20.    The test for PKU used to be known by the name of its inventor. Who was he and why

did he have a particular interest? There is no option list and no one is going to ask you except me!

Question 21.     What conditions are covered in the routine neonatal ‘heelprick’ screening test?

Question 22.    Is neonatal screening for PKU still done using the bacterial inhibition method? If not,

what method is used? There is no option list.

Question 23.    What is the main treatment of PKU and what are its problems?

Question 24.    How long should the main treatment of PKU be continued and why?

Question 25.    A woman with PKU is planning her first pregnancy at the age of 22. She has been off

the PKU-restricted diet since the age of 10 and can barely remember being on it. Should she be advised to re-start the diet? If ‘yes’, when should she start and what explanation would you give for the advice?

Question 26.    Which if any of the following statements are true about screening for PKU and its

effects in the neonate born to a woman with PKU ?

Option list.

A	routine bloodspot screening alone is required
B	the neonate should be examined by a paediatrician for signs of PKU
C	the baby should have developmental assessment, even if it does not have PKU
D	an ultrasound scan should be done because of the increased risk of developmental dysplasia of the hip
E	the baby should be started on a low PA diet until all assessments are complete
F	none of the above.

Question 27.    Is breast-feeding advisable for women with PKU?

Question 28.    Are any other therapeutic approaches available? If ‘yes’, what are they and how do

they work? If ‘yes’ use the option list for the mode of action.

Option List

A	it binds PA to circulating plasma proteins, reducing its free levels
B	it increases hepatic metabolism of PAH.
C	it increases renal excretion of PA
D	it is a co-factor for PAH, increasing its efficacy in reducing PA levels
E	it is phenylalanine ammonia lyase, capable of breaking down PA
F	it is a synthetic PAH enzyme
G	it reduces absorption of PA from the small bowel

Question 29.    Is PIGD for PKU available on the NHS? Yes / No?

Question 30.    Which organisation regulates PIGD in the UK?

 

TOG CPD questions. These are open-access, so reproduced here.

Regarding phenylketonuria (PKU):

1.        it is a deficiency of the amino acid phenylalanine (Phe).                       True  False

2.        it is an X-linked recessive inherited metabolic disease.                         True  False

3.        it results in a deficiency in the amino acid tyrosine.                              True  False

4.        it is treated with a low-phenylalanine restricted diet.                           True  False

5.        the incidence is approximately 1:1000.                                                    True  False

6.        the Newborn Screening Programme has been a great success in the diagnosis and management of children with PKU.                                               True  False

7.        neonates with fetal alcohol syndrome and PKU are clinically difficult to distinguish at birth.                                                                                                                             True  False

8.        in utero exposure to very high levels of phenylalanine results in reversible neurological damage to the fetus.                                                                                     True  False

9.        pregnancy outcome is improved substantially when treatment results in low maternal phenylalanine concentrations ideally before conception.                                       True  False

10.      oral methods of contraception should be switched to barrier methods at least 12 months before conception.                                                                               True  False

11.      the risk of congenital heart defects is estimated to be 7–10%.           True  False

12.      it is an indication for early delivery by caesarean section.                    True  False

13.      neonates born to mothers with PKU should be offered screening for PKU as per the routine national screening programme.                                                                  True  False

14.      breastfeeding is contraindicated in women with PKU.                          True  False

With regard to the biochemistry of PKU:

15.      Phe is passively transported across the placenta.                                  True  False

16.      fetal Phe levels are approximately 1.25-2.5 times > than maternal levels.      True  False

Children born to women with PKU:

17.      tend to have blue eyes.                                                                               True  False

18.      are fair skinned.                                                                                            True  False

With regard to the effect of high Phe levels on loss of IQ or behavioural changes:

19.      these changes are reversible in utero.                                                      True  False

20.      they are reversible with resumption of diet deficient of Phe.              True  False

 

33.   Hepatitis D. Hepatitis Delta.

Abbreviations:

HBsAg:      hepatitis B surface antigen

HBsAb:      antibody to hepatitis B surface antigen

HBV:          hepatitis B virus

HCsAg:      hepatitis C surface antigen

HDV:          hepatitis D virus; hepatitis delta virus

HEsAg:      hepatitis E surface antigen

Question 1.             Which, if any, of the following statements are true in relation to HDV? This is not a true EMQ as there may be >1 correct answer.

Option list.

A	HDV is a large DNA virus
B	HDV is a defective virus
C	HDV gains entry to human cells via the HDV receptor
D	HDV gains entry to human cells by donning a disguise and using the HBV receptor
E	HDV only flourishes when HBsAb is present
F	HDV only flourishes when HBsAg is present
G	Coi   coinfection is when HDV and another viral infection are present at the same time
H	Susu superinfection is when HDV is present in abnormally high numbers
I	HDV infection is the least serious of the viral hepatitides in relation to pregnancy
J	HDV treatment was revolutionised by analysis of the benefits of drinking bleach as suggested by Donald Trump
K	the   WHO has recommended that those who follow medical advice from Donald trump should be categorised as ‘having the DTs’.
L	HDV needs the presence of HBsAg to be a significant pathogen
M	HDV needs the presence of HCsAg to be a significant pathogen
N	HDV needs the presence of HEsAg to be a significant pathogen
O	ppe  pegylated interferon alpha is highly effective as treatment
P	m     mother-to-child transmission is mainly via the placenta
Q	WHO recommends tenofovir prophylaxis from 28 weeks in pregnancy in HDV infected women
R	the   infected neonate should be given HDV vaccine

 

 

 

34.   Cervical cancer staging.

Cervical cancer staging.

Option list.

A	Micro-invasive cervical cancer.
B	Stage IA1
C	Stage IA2
D	Stage IA3
E	Stage IB1
F	Stage IB2
G	Stage IB3
H	Stage IIA
I	Stage IIB
J	Stage IIC
K	Stage IIIa
L	Stage IIIB
M	Stage IIIC
N	Stage IVA
O	Stage IVB
P	Stage IVC
Q	Stage VA
R	Stage VB
S	Stage VC
T	None of the above.

Scenario 1. A woman of 25 has a cone biopsy. The histology report shows squamous cell carcinoma penetrating to a depth of 2 mm and 6 mm in width. The resection margins are tumour-free. There is no evidence of spread outside the uterus. She is nulliparous and wishes to retain her fertility.

Scenario 2. A woman of 25 has a cone biopsy. The histology report shows squamous cell carcinoma penetrating to a depth of 4 mm and 6 mm in width. The resection margins are tumour-free. There is no evidence of spread outside the uterus. She is nulliparous and wishes to retain her fertility.

Scenario 3. A woman of 25 has a cone biopsy. The histology report shows squamous cell carcinoma penetrating to a depth of 5 mm and 6 mm in width. The resection margins are not tumour-free. There is no evidence of spread outside the uterus. She is nulliparous and wishes to retain her fertility.

Scenario 4. A woman of 25 has a cone biopsy. The histology report shows squamous cell carcinoma penetrating to a depth of 6 mm and 3 cm in width. The resection margins are tumour-free. There is no evidence of extension outside the cervix. She is nulliparous and wishes to retain her fertility.

Scenario 5. A woman of 25 has a cone biopsy. The histology report shows squamous cell carcinoma penetrating to a depth of 6 mm and 5 cm in width. The resection margins are tumour-free. She is nulliparous and wishes to retain her fertility.

Scenario 6. A woman of 38 has a cone biopsy. The histology report shows squamous cell carcinoma penetrating to a depth of 4 mm and 6mm in width. The resection margins are tumour-free. An MR scan shows involvement of the lymphatic nodes in the left of the pelvis.

Scenario 7. A woman of 45 has carcinoma of the cervix. It extends into the parametrium, but not to the pelvic sidewall. It involves the upper 1/3 of the vagina. There is MRI evidence of para-aortic node involvement.

Scenario 8. A woman of 55 has carcinoma of the cervix. It extends to the pelvic sidewall. It involves the upper 1/3 of the vagina. She has a secondary on the end of her nose.

Scenario 9. A woman of 55 has carcinoma of the cervix. It involves the bladder mucosa.

Scenario 10. A woman of 35 has a proven cancer of the cervix with extension into the right parametrium, but not to the pelvic sidewall. Left hydroureter and left non-functioning kidney are noted on IVP and there is no other explanation for the findings. Cystoscopy shows bullous oedema of the bladder mucosa.

Scenario 11. A woman of 25 has a cone biopsy. It shows malignant melanoma. The lesion, which was not visible to the naked eye, invades to a depth of 3 mm and is 5 mm in width. The margins of the biopsy are clear. There is evidence of lymphatic vessel involvement. There is no evidence of spread outside the uterus.