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80

Tutorial. Julie Morris. Medical statistics

81

EMQ. Phenylketonuria

82

EMQ. Headache

 81. Julie Morris. Medical statistics tutorial.

 82. EMQ. Phenylketonuria.

Abbreviations.

PA:             phenylalanine.

PAH:          phenylalanine hydroxylase.

PAHD:       phenylalanine hydroxylase deficiency.

PKU:          phenylketonuria.

Tyr:            tyrosine.

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 is 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 relevant 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.

Option List

H.      

1 in 1,000

I.        

1 in 2,500

J.        

1 in 5,000

K.      

1 in 10,000

L.       

1 in 100,000

M.    

1 in 150,000

N.      

1 in 200,000

O.     

1 in 1,000,000

 

Ethnic group

Prevalence

Turkish

1 in 2,600

Irish

1 in 4,500

Caucasian

1 in 10,000

East Asian

1 in 10,000

Japanese

1 in 143,000

Finnish

1 in 200,000

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 PKU levels higher or lower than maternal? There is no option list.

Question 17.      

Which, if any, of the following  are true in relation to the maternal phenylketonuria 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 PKU in the mother?

Question 19.      

Is screening for PKU a routine part of the neonatal screen 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 included in the routine neonatal ‘heelprick’ screening test? There is no option list.

Question 22.      

Is neonatal screening for PKU still done using Guthrie’s 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 problems are associated with it? There is no option list.

Question 24.      

How long should the main treatment of PKU be continued and why? There is no option list.

Question 25.      

Lead-in

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.      

Lead-in

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.      

Lead-in

Is breast-feeding advisable for women with PKU?

Question 28.      

Lead-in

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

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

 

83. EMQ. Headache.

Option list.

1.      abdominal migraine

2.      analgesia overuse, aka medication overuse

3.      bacterial meningitis

4.      benign intracranial hypertension

5.      BP check

6.      cerebral venous sinus thrombosis

7.      chest X-ray

8.      cluster

9.      severe PET / impending eclampsia

10.  malaria

11.  meningococcal meningitis

12.  methyldopa

13.  methysergide

14.  migraine

15.  MRI brain scan

16.  nifedipine

17.  nitrofurantoin

18.  pancreatitis

19.  sinusitis

20.  subdural haematoma

21.  subarachnoid haemorrhage

22.  tension

23.  ultrasound scan of the abdomen

Scenario 1.

A 40-year-old para 3 is admitted at 38 weeks by ambulance with severe headache of sudden onset. She describes it as “the worst I’ve ever had”. Which diagnosis needs to be excluded urgently?

Scenario 2.

A 32-year-old para 1 has recently experienced headaches. They are worse on exercise, even mild exercise such as walking up stairs. She experiences photophobia with the headaches. Which is the most likely diagnosis?

Scenario 3.

A woman returns from a sub-Saharan area of Africa. She develops severe headache, fever and rigors. What diagnosis should particularly be in the minds of the attending doctors?

Scenario 4.

A woman at 37 weeks has s. They particularly occur at night without obvious triggers. They occur every few days.

Scenario 5.

A primigravida has had s on a regular basis for many years. They occur most days, are bilateral and are worse when she is stressed. What is the most likely diagnosis?

Scenario 6.

A woman complains of recent headaches at 36 weeks. The history reveals that they started soon after she began treatment with a drug prescribed by her GP. Which is the most likely of the following drugs to be the culprit: methyldopa, methysergide, nifedipine or nitrofurantoin?

Scenario 7

A woman is booked for Caesarean section and wishes regional anaesthesia. She had severe headache due to dural tap after a previous Caesarean section. She wants to take all possible steps to reduce the risk of having this again. Which of epidural / spinal anaesthesia has the lower risk of causing dural tap?

Scenario 8

A 25-year-old primigravida attends for her 20-week scan and complains of headache which started two weeks before. There is no significant history. The pain occurs behind her right eye and she describes it as severe and “stabbing” in nature. The pain is so severe that she cannot sit still and has to walk about. She has noticed that her right eye becomes reddened and “watery” during the attack and her nose is “runny”. The attacks have no obvious trigger and mostly occur a few hours after she has gone to sleep. The usually last about 20 minutes. She has no other symptoms. She smokes 20 cigarettes a day but does not take any other drugs, legal or otherwise. What is the most likely diagnosis?

Scenario 9

A woman has a 5-year history of unilateral, throbbing headache often preceded by nausea, visual disturbances, photophobia and sensitivity to loud noise. What is the most likely diagnosis?

Scenario 10

A primigravida is admitted at 38 weeks complaining of headache, abdominal pain and a sensation of flashing lights. What would be the appropriate initial investigation?

Scenario 11

A woman with BMI of 35 attends for her combined Downs syndrome screening test. She complains of pain behind her eyes. The pain is worst last thing at night before she goes to sleep or if she has to get up in the night. She has noticed she has noticed horizontal diplopia on several occasions. She has no other symptoms. Examination shows papilloedema.

Scenario 12

A grande multip of 40 years experienced sudden-onset, severe headache, vomited several times and then collapsed, all within the space of 30 minutes. She is admitted urgently in a semi-comatose state. Examination shows neck-stiffness and left hemi-paresis.

Scenario 13.

What did the MMR include as “red flags” for headache in pregnancy? These are not on the option list – you need to dig them out of your head.

Scenario 14.

This is not an EMQ. It relates to the incidence of various conditions in women who have migraine. Choose the appropriate arrow for each.

Option list.

A

asthma

B

developmental dysplasia of the hip in child

C

diabetes

D

Down’s syndrome in child

E

hypertension

F

ischaemic heart disease

G

PET

H

stroke

Scenario 15.

Which of the following drugs is contraindicated in the prophylaxis of migraine in pregnancy?

Option list.

A

amitriptyline

B

ß-blockers

C

ergotamine

D

low-dose aspirin

E

pizotifen

F

pregabalin

G

tricyclic antidepressants

H

verapamil

Scenario 16.

Which, if any, of the following statements is true about posterior reversible encephalopathy syndrome. This is not a true EMQ as there may be > 1 true answer.

Option list.

A

‘thunderclap’ headache is typical

B

‘handclap’ headache is typical

C

classically occurs in the early puerperium and is recurrent

D

classically occurs in the early puerperium and is not recurrent

E

arterial beading is typically seen on MRI

F

arterial beating is typically seen on MRI

G

arterial bleeding is typically seen on MRI

H

venous beading is typically seen on MRI

I

venous beating is typically seen on MRI

J

venous bleeding is typically seen on MRI

K

diagnosis requires lumbar puncture and evidence of ↑ CSF pressure

L

treatment is with nimodipine

Scenario 17.

Which, if any, of the following statements is true about reversible cerebral vasoconstriction syndrome. This is not a true EMQ as there may be > 1 true answer.

Option list.

A

‘thunderclap’ headache is typical

B

‘handclap’ headache is typical

C

classically occurs in the early puerperium and is recurrent

D

classically occurs in the early puerperium and is not recurrent

E

arterial beading is typically seen on MRI

F

arterial beating is typically seen on MRI

G

arterial bleeding is typically seen on MRI

H

venous beading is typically seen on MRI

I

venous beating is typically seen on MRI

J

venous bleeding is typically seen on MRI

K

diagnosis requires lumbar puncture and evidence of ↑ CSF pressure

L

treatment is with nimodipine

 

Questions from TOG article by Revell & Moorish. 2014. These are open access.

You can find the questions here.

Headaches in pregnancy

Red flag features for headaches include:

1.     headache that changes with posture                                                       True / False

2.     associated vomiting                                                                                      True / False

3.     occipital location                                                                                           True / False

4.     associated visual disturbance.                                                                   True / False

Migraine is classically,

5.     bilateral.                                                                                                           True / False

6.     pulsating.                                                                                                         True / False

7.     aggravated by physical exercise.                                                               True / False

With regard to migraine headaches in pregnancy,

8.     there is an increase in the frequency of attacks without aura.                      True / False

9.     women who suffer from this have not been shown to have an increase in the risk of pre-eclampsia.                                                                                              True / False

10. the 5HT1-receptor sumatriptan has been shown to be teratogenic.           True / False

11. women presenting with an aura for the first time are not at an increased risk of intracranial disease.                                                                             True / False

Posterior reversible encephalopathy syndrome,

12. is associated with an impairment of the autoregulatory mechanism which maintains constant cerebral blood flow where there are blood pressure fluctuations. True / False

13. when it is associated with pre-eclampsia, management should follow the pathway for managing severe pre-eclampsia.                                                               True / False

With regard to cerebral venous thrombosis,

14. the incidence in western countries in pregnancy ranges from 1 in 2500 deliveries to 1 in 10 000 deliveries.                                                                                          True / False

15.   the greatest risk in pregnancy is mainly in the last four weeks.            True / False

16. the most common site is the sagittal sinus.                                           True / False

17. a plain computed tomography is a highly sensitive investigation.        True / False

18. T2-weighted magnetic resonance imaging has been shown to have limited value in diagnosis.                                                                                                            True / False

19. the outcome is better when it is associated with pregnancy and the puerperium compared to that occurring outside pregnancy.                                        True / False

20. when it occurs in pregnancy, it is a contraindication for future pregnancies. True / False