Porphyria Flashcards
Acute Intermittent Porphyria
Acute intermittent porphyria (AIP) is a rare autosomal dominant condition caused by a defect in porphobilinogen deaminase, an enzyme involved in the biosynthesis of haem. The results in the toxic accumulation of delta aminolaevulinic acid and porphobilinogen. It characteristically presents with abdominal and neuropsychiatric symptoms in 20-40 year olds. AIP is more common in females (5:1)
Features abdominal: abdominal pain, vomiting neurological: motor neuropathy psychiatric: e.g. depression hypertension and tachycardia common
Diagnosis
classically urine turns deep red on standing
raised urinary porphobilinogen (elevated between attacks and to a greater extent during acute attacks)
assay of red cells for porphobilinogen deaminase
raised serum levels of delta aminolaevulinic acid and porphobilinogen
Acute Intermittent Porphyria - Example Question
A 30-year-old woman presents to the emergency department with severe, progressive abdominal pain over the past day. The pain is accompanied by nausea, vomiting and diarrhoea. The patient recalls similar episodes in the past that progressed over a few days and lasted for a week. Temperature is 37°C, blood pressure is 140/100 mmHg, pulse is 120/min and respirations are 16/min.
On examination: minimal abdominal tenderness and rebound tenderness. She has a history of abdominal surgery for suspected appendicitis and biliary disease, neither of which was confirmed once inside the abdomen.
Which of the following will help to confirm the diagnosis?
Erythrocyte porphyrins Faecal porphyrins Plasma porphyrins > Urine porphobilinogen Urine porphyrins
This patient has acute intermittent porphyria, which classically presents with neurovisceral symptoms which can mimic an acute abdomen. This mimicry occurs because the abdominal pain is produced by a nerve problem rather than inflammation, hence why exploratory surgery is uneventful. In long-standing cases, patients may have damage to their motor nerves resulting in upper limb weakness.
Porphyrias
Overview
abnormality in enzymes responsible for the biosynthesis of haem
results in overproduction of intermediate compounds (porphyrins)
may be acute or non-acute
Acute Intermittent Porphyria
Acute intermittent porphyria (AIP)
autosomal dominant
defect in porphobilinogen deaminase
female and 20-40 year olds more likely to be affected
typically present with abdominal symptoms, neuropsychiatric symptoms
hypertension and tachycardia common
urine turns deep red on standing
Porphyria Cutanea Tarda
Porphyria cutanea tarda (PCT)
most common hepatic porphyria
defect in uroporphyrinogen decarboxylase
may be caused by hepatocyte damage e.g. alcohol, oestrogens
classically photosensitive rash with bullae, skin fragility on face and dorsal aspect of hands
urine: elevated uroporphyrinogen and pink fluorescence of urine under Wood’s lamp
manage with chloroquine
Variegate Porphyria
Variegate porphyria autosomal dominant defect in protoporphyrinogen oxidase photosensitive blistering rash abdominal and neurological symptoms more common in South Africans
Porphyria Cutanea Tarda - Example Question
A 54-year-old alcoholic man with chronic hepatitis C is taken to the emergency department by the police. There it was noted that the man had blisters and crusted lesions on his face and lower arms.
Laboratory tests showed elevated plasma porphyrins and elevated uroporphyrin I in the urine, and isocoproporphyrin in the faeces. Biopsy of the skin lesion showed subepidermal blisters with minimal inflammation, marked solar elastosis, thickening of the vessel wall in the papillary dermis and ‘caterpillar bodies’ in the roof of the blister.
Which of the following is the most likely diagnosis?
Acute intermittent porphyria Delta-aminolevulinic acid dehydrase deficiency Erythropoietic protoporphyria Hereditary coproporphyria > Porphyria cutanea tarda
Porphyria cutanea tarda causes chronic blistering and crusting skin lesions on sun-exposed skin. Precipitating factors: iron (even if normal amounts), oestrogen and alcohol use, and chronic hepatitis C infection.
The findings on skin biopsy can help with the diagnosis but are not very specific (the ‘caterpillar bodies’ are essentially clumps of basement membrane material). The key to the diagnosis is the presentation and porphyrin analysis.
Mx of Acute Psychosis in Acute Intermittent Porphyria
CHLORPROMAZINE
NB Benzodiazepines are unsafe
Acute Intermittent Porphyria - Example Presentation
NEUROPSYCHIATRIC, ABDO PAIN (Recurrent), HTN, TACHYCARDIA, HYPONATRAEMIA
Acute Intermittent Porphyria
AIP is an autosomal dominant condition caused by a defect in porphobilinogen deaminase - an enzyme involved in the biosynthesis of Haem. Characteristically presents w abdominal and neuropsychiatric Sx in 20-40yr olds. More common in F 5:1
AIP - Drugs which may precipitate attack
Barbiturates Halothane Benzodiazepines Alcohol COCP Sulphonamides
Drugs considered safe to use:
- Paracetamol
- Aspirin
- Codeine
- Morphine
- Chlorpromazine
- Beta-Blockers
- Penicillin
- Metformin
Acute Porphyria - Example Question
A 31-year-old lady presents to the emergency department with abdominal pain.
Her medical and surgical history is unremarkable other than mild depression and hay fever. Medications include paroxetine and PRN loratadine.
She complains of generalised colicky abdominal pain and has vomited once in the department.
On examination blood pressure is 155/86mmHg, heart rate is 95bpm and temperature is 37.9ºC. Digital rectal examination reveals hard stool in the rectum.
Investigations reveal:
Hb 131 g/l Platelets 362 * 109/l WBC 7.3 * 109/l Na+ 121 mmol/l K+ 3.3 mmol/l Urea 6.2 mmol/l Creatinine 87 µmol/l Urine dipstick protein ++, leucocytes ++
What is the most likely diagnosis?
Cholecystitis > Acute porphyria Intestinal obstruction Pyelonephritis Systemic lupus erythematosus
The normal white cell count make infective diagnoses such as pyelonephritis and cholecystitis less likely. Intestinal obstruction usually presents with an empty rectum.
The history of neuropsychiatric symptoms along with hypertension and hyponatraemia are suggestive of acute porphyria.
Systemic lupus erythematosus doesn’t tend to present with abdominal pain.
The Porphyrias
The porphyrias are a group of rare inborn errors of metabolism caused by abnormalities of enzymes involved in the biosynthesis of haem, resulting in overproduction of intermediate compounds called porphyrins.
Three patterns of symptoms occur clinically with porphyrias:
1) Neurovisceral - neuropathy, epilepsy, psychiatric disorders, abdominal, vomiting, constipation
2) Photosensitive - bullous eruption in sun exposed areas
3) Haemolytic
NEUROVISCERAL only:
- Acute Intermittent Porphyria
- Aminolaevulinic acid dehydrogenase porphyria
PHOTOSENSITIVE only:
- Congenital erythropoietic porphyria
- Erythropoietic protoporphyria
- PCT?
Mixed Neurovisceral and Photosensitive:
- Hereditary coproporphyria
- Variegate Porphyria
Porphyria - Which type? Example Question
A 34 year old man is admitted under the medics from the emergency department with central abdominal pain and vomiting not responding to IV morphine. He had been seen by the surgeons earlier in the day as an acute abdomen, but the CT scan they did of his abdomen and pelvis revealed no abnormalities, and his bloods suggested no surgical cause of the abdominal pain.
You note that the patient has presented to the emergency department five times in the past two years with similar problems, and no cause has ever been found, with the patient being discharged one or two days later with analgesia.
On examination his abdomen is generally tender with evidence of voluntary guarding. On further examination you note that he has a rash on the back of his hands, neck and cheeks. This rash consists of several small fluid filled bullae.
His past medical history includes depression - for which he is taking citalopram, and one short psychiatric inpatient stay for an episode of psychosis.
What is the most likely diagnosis?
Erythropoietic protoporphyria Porphyria cutanea tarda > Hereditary coproporphyria Acute intermittent porphyria Congenital erythropoietic porphyria
This patient has both photosensitive symptoms; his rash, and neurovisceral symptoms; abdominal pain and previous psychiatric history. The only mixed presentation porphyria given as a possible answer is hereditary coproporhyria, hence it is the correct answer.
Acute Intermittent Porphyria - Example Question
A 24-year-old female presents to the emergency department with severe abdominal pain which had developed over for the last few hours. The pain was central, severe and stabbing in nature associated with vomiting. She was in hysterics and was extremely agitated and confused. Past medical history included asthma and depression. Two days earlier she had seen her GP for dysuria and been prescribed trimethoprim.
She was a student studying chemistry at university and had recently been out late several nights drinking excess alcohol to celebrate passing her exams. On examination, she was unwell, extremely clammy, distressed with generalised abdominal tenderness and weakness in both legs with areflexia. Heart sounds and chest were clear. Observations showed a blood pressure 190/100 mmHg, heart rate 126/min, regular and temperature 37.9ºC.
Which investigation is most likely to be diagnostic?
Urinary catecholamines Abdominal ultrasound > Urinary porphobilinogen Lumbar puncture Blood cultures
This patient has acute intermittent porphyria (AIP). AIP is the most common type of porphyria. AIP is an autosomal dominant condition caused by a genetic mutation in the gene encoding the enzyme porphobilinogen (PBG) deaminase on chromosome 11. The condition is more common in females than males and usually occurs between the ages 14-30 years. Porphyrias occur due to a problem within the haem biosynthesis. Defective PBG deaminase causes PBG to accumulate and this can be found in the urine. Attacks are usually precipitated by drugs, alcohol, fasting and sepsis. This patients attack has been caused by a combination of antibiotic use and alcohol intake.
Patients most commonly present with gastrointestinal symptoms (most commonly severe abdominal pain) neurological symptoms (autonomic dysfunction, peripheral motor neuropathies, areflexia, delirium, seizures, coma) and psychiatric symptoms such as common. Observations commonly show tachycardia and hypertension. Fever can be present. Most patients are completely free of symptoms between attacks.
The treatment for acute attacks of porphyria is to decrease haem synthesis and reduce the production of porphyrin precursors. Withdrawal of culprit medication is essential. A high-calorie intake and high doses of glucose can help inhibit haem synthesis and are useful for the treatment of mild attacks. In severe attacks, intravenous haematin is used. Pain is treated with narcotics. Beta blockers can be used to treat tachycardia and hypertension.
Advice can be obtained from National Acute Porphyria Centres: Cardiff, Kings College Hospital, London and Cambridge
