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MRCP Biochemistry: Porphyrias & Heme Synthesis

TL;DR

Porphyrias and heme synthesis are classic MRCP Part 1 biochemistry topics that test pattern recognition rather than deep molecular detail. Focus on where the pathway breaks, the dominant clinical features (neurovisceral vs cutaneous), and the single best investigation or treatment. Master these themes and you secure straightforward marks.


Why this matters

Porphyrias sit at the crossroads of biochemistry, neurology, psychiatry, and dermatology—exactly the kind of integration MRCP Part 1 rewards. Questions are usually short and discriminating, built around a clinical vignette with one or two biochemical clues. Candidates commonly lose marks by memorising the entire pathway but missing the clinical pattern.

In practice, recognising porphyria quickly prevents over-investigation in the exam stem and helps eliminate distractors. If you want context on how such topics are assessed overall, start with the MRCP Part 1 overview.


Scope of porphyrias & heme synthesis for MRCP Part 1

You are not expected to reproduce the full heme pathway from memory. The exam focuses on:

  • The site of the defect (hepatic vs erythropoietic).

  • The clinical phenotype (acute neurovisceral vs cutaneous photosensitivity).

  • A key investigation or trigger that points to the diagnosis.

Heme synthesis: what examiners actually test

Heme synthesis occurs partly in mitochondria and partly in the cytosol. The rate-limiting step is catalysed by ALA synthase, which is induced by drugs, alcohol, and fasting. MRCP questions usually hinge on what happens when this regulation goes wrong, rather than on naming every intermediate.


High-yield facts you must know

  1. ALA synthase is the rate-limiting enzyme and is upregulated by enzyme-inducing drugs.

  2. Acute intermittent porphyria (AIP) causes neurovisceral symptoms without photosensitivity.

  3. Porphyria cutanea tarda (PCT) is the commonest porphyria seen in practice and exams.

  4. Dark or “port-wine” urine on standing suggests excess porphyrins or precursors.

  5. Hyponatraemia in AIP is commonly due to SIADH.

  6. Acute attacks are precipitated by drugs, alcohol, and fasting.

  7. Haem (haem arginate) is used to treat acute neurovisceral attacks.

  8. Lead poisoning can mimic porphyria by inhibiting heme synthesis enzymes.


The five most tested porphyrias

1. Acute intermittent porphyria

  • Defect: Porphobilinogen deaminase.

  • Features: Abdominal pain, psychiatric symptoms, peripheral neuropathy.

  • Exam pearl: Recurrent abdominal pain with normal imaging and no photosensitivity.

2. Porphyria cutanea tarda

  • Defect: Uroporphyrinogen decarboxylase.

  • Features: Blistering photosensitivity, skin fragility, hyperpigmentation.

  • Associations: Alcohol excess, hepatitis C, haemochromatosis.

3. Variegate porphyria

  • Features: Mixed neurovisceral and cutaneous symptoms.

  • Exam pearl: Both abdominal pain and photosensitivity in the same patient.

4. Erythropoietic protoporphyria

  • Features: Painful photosensitivity from childhood.

  • Exam pearl: Immediate pain on sun exposure rather than blistering.

5. Drug-induced porphyria exacerbation

  • Mechanism: Enzyme induction increases ALA synthase activity.

  • Exam pearl: Symptoms worsen after starting a new medication.


Common exam traps (and how to avoid them)

  • Assuming all porphyrias cause photosensitivity → remember AIP does not.

  • Confusing PCT with autoimmune blistering disease → check liver risk factors.

  • Over-interpreting genetics → most questions are clinical, not molecular.

  • Ignoring precipitating factors → drugs and fasting are key clues.

  • Choosing imaging over biochemistry → urinary porphobilinogen is often correct.

MRCP Part 1 biochemistry revision setup showing textbooks, notes and laptop.

Key comparison table

Feature

Acute Intermittent Porphyria

Porphyria Cutanea Tarda

Main symptoms

Abdominal pain, neuropathy

Blistering photosensitivity

Photosensitivity

No

Yes

Common triggers

Drugs, fasting

Alcohol, liver disease

Key test

↑ Urinary PBG

↑ Uroporphyrins

Typical treatment

Haem + glucose

Venesection, avoid triggers

Mini-case (MRCP style)

A 29-year-old woman presents with severe abdominal pain, anxiety, and tingling in her feet. CT abdomen is normal. She recently started an antiepileptic drug. Her urine darkens on standing.

Diagnosis: Acute intermittent porphyria. Why: Neurovisceral symptoms, drug trigger, normal imaging, absence of photosensitivity.

Practising similar vignettes under time pressure—using Free MRCP MCQs or a timed mock test—helps cement this recognition.


Practical study-tip checklist

  • Learn porphyrias by clinical pattern, not by memorising pathways.

  • Pair each porphyria with one enzyme + one hallmark feature.

  • Memorise common precipitating drugs and lifestyle triggers.

  • Practise at least 10–15 porphyria questions in mixed blocks.

  • Revisit mistakes and note why distractors were wrong.


FAQs

Are porphyrias commonly tested in MRCP Part 1?

Yes. They appear regularly, usually as short clinical vignettes testing pattern recognition.

Do I need the full heme pathway for the exam?

No. Focus on rate-limiting steps, major enzyme defects, and clinical consequences.

Which porphyria is most high-yield?

Acute intermittent porphyria and porphyria cutanea tarda are the most frequently examined.

What is the best initial investigation in suspected AIP?

Raised urinary porphobilinogen during an acute attack.

How should I revise porphyrias efficiently?

Use mixed biochemistry question blocks and timed practice to train rapid recognition.


Ready to start?

For structured revision and exam-style practice, start with the MRCP Part 1 overview, reinforce learning with the Qbank, and test readiness using mock tests.


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