Metab: Porphyrias: Acute Intermittent vs Cutanea Tarda for MRCP Part 1
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TL;DR:
Metab: Porphyrias: Acute Intermittent vs Cutanea Tarda is a classic MRCP Part 1 topic that tests your understanding of haem biosynthesis disorders. Acute Intermittent Porphyria (AIP) presents with acute neurovisceral symptoms without photosensitivity, whereas Porphyria Cutanea Tarda (PCT) causes chronic blistering photosensitivity without neurological attacks. Most MRCP questions can be answered by recognising the clinical presentation, enzyme defect, biochemical findings, and common triggers.
Porphyrias are uncommon disorders in clinical practice but disproportionately important in MRCP Part 1 examinations. They combine principles from metabolism, hepatology, neurology, dermatology, genetics, and biochemistry, making them ideal examination material. Among the various porphyrias, Acute Intermittent Porphyria (AIP) and Porphyria Cutanea Tarda (PCT) are by far the most frequently tested.
For a broader overview of the MRCP syllabus, visit the MRCP Part 1 hub:
Why This Topic Matters
The porphyrias arise from defects in the haem biosynthesis pathway. Each enzymatic defect leads to accumulation of specific intermediates, producing characteristic clinical syndromes.
MRCP questions commonly focus on:
Recognising acute neurovisceral attacks
Identifying photosensitive skin disorders
Understanding enzyme deficiencies
Recognising biochemical abnormalities
Choosing appropriate investigations
Understanding treatment principles
AIP and PCT are often compared directly because their presentations are almost opposite.
Understanding Haem Biosynthesis
Haem is synthesised primarily in:
The liver
The bone marrow
Defects in haem synthesis result in accumulation of toxic intermediates.
A useful examination rule is:
Accumulation of early haem precursors tends to cause neurological symptoms, while accumulation of porphyrins causes photosensitivity.
This principle explains the contrasting presentations of AIP and PCT.
The Five Most Tested Subtopics
1. Enzyme Defects
Acute Intermittent Porphyria
Deficiency of porphobilinogen deaminase
Also known as hydroxymethylbilane synthase deficiency
Usually inherited in an autosomal dominant fashion
Porphyria Cutanea Tarda
Deficiency of uroporphyrinogen decarboxylase
Most common porphyria worldwide
Often acquired rather than purely inherited
2. Clinical Presentation
Acute Intermittent Porphyria
Key clinical features include:
Severe abdominal pain
Nausea and vomiting
Constipation
Peripheral neuropathy
Psychiatric disturbances
Anxiety and depression
Seizures
Hypertension
Tachycardia
The classic examination clue is:
Severe abdominal pain with a relatively normal abdominal examination.
Importantly:
Photosensitivity is absent.
Porphyria Cutanea Tarda
Typical features include:
Blistering photosensitive rash
Fragile skin
Hyperpigmentation
Hypertrichosis
Skin erosions on sun-exposed areas
Chronic liver disease associations
Importantly:
Neurological symptoms are absent.
3. Important Triggers
Acute Intermittent Porphyria
Common precipitants include:
Alcohol
Fasting
Infection
Smoking
Progesterone
Sulphonamides
Rifampicin
Enzyme-inducing antiepileptics
Many attacks occur after medications induce hepatic cytochrome P450 enzymes.
Porphyria Cutanea Tarda
Common associations include:
Iron overload
Alcohol excess
Hepatitis C infection
Oestrogen therapy
Smoking
HIV infection
Questions frequently describe a patient with blistering photosensitivity and abnormal liver function tests.
4. Laboratory Diagnosis
Feature | Acute Intermittent Porphyria | Porphyria Cutanea Tarda |
Main manifestation | Neurovisceral | Cutaneous |
Photosensitivity | No | Yes |
Abdominal pain | Common | Rare |
Neuropathy | Common | Absent |
Urinary porphobilinogen | Increased | Usually normal |
Urinary ALA | Increased | Usually normal |
Uroporphyrin accumulation | No | Yes |
Liver disease association | Weak | Strong |
Typical age | Young adults | Middle-aged adults |
High-yield MRCP point:
Elevated urinary porphobilinogen during an acute attack strongly suggests Acute Intermittent Porphyria.
5. Management
Acute Intermittent Porphyria
Management includes:
Withdrawal of precipitating drugs
Intravenous haem therapy
High-carbohydrate intake
Symptomatic management
Correction of electrolyte disturbances
Hyponatraemia is a classic examination association.
Porphyria Cutanea Tarda
Management includes:
Venesection
Reduction of iron overload
Alcohol cessation
Treatment of hepatitis C when present
Low-dose hydroxychloroquine in selected patients
10 High-Yield MRCP Revision Points
AIP is caused by porphobilinogen deaminase deficiency.
PCT is caused by uroporphyrinogen decarboxylase deficiency.
AIP causes severe abdominal pain.
AIP causes neuropathy and psychiatric symptoms.
Photosensitivity is absent in AIP.
PCT presents with blistering photosensitivity.
Hepatitis C is strongly associated with PCT.
Iron overload is an important risk factor for PCT.
Urinary porphobilinogen rises during acute AIP attacks.
Venesection is a cornerstone of PCT treatment.
Practical Example
Mini-MCQ
A 30-year-old woman presents with recurrent severe abdominal pain, constipation, tachycardia, and confusion. Physical examination of the abdomen is unremarkable. Blood tests reveal hyponatraemia. She recently started an antiepileptic medication.
What is the most likely diagnosis?
A. Porphyria Cutanea TardaB. Acute Intermittent PorphyriaC. Wilson DiseaseD. HaemochromatosisE. Polyarteritis Nodosa
Answer
B. Acute Intermittent Porphyria
Explanation
The combination of:
Severe abdominal pain
Minimal abdominal findings
Hyponatraemia
Neuropsychiatric symptoms
Drug trigger
is highly characteristic of Acute Intermittent Porphyria.
Practical Study-Tip Checklist
Before sitting the examination, ensure you can immediately recall:
□ Enzyme defect in AIP
□ Enzyme defect in PCT
□ Presence or absence of photosensitivity
□ Presence or absence of neuropathy
□ Common triggers of AIP
□ Hepatitis C association with PCT
□ Diagnostic urinary marker for AIP
□ Role of venesection in PCT
□ Causes of hyponatraemia in AIP
□ First-line treatment principles for both disorders
Common MRCP Pitfalls
Confusing photosensitivity with Acute Intermittent Porphyria.
Forgetting that AIP often presents with a normal abdominal examination.
Missing the association between hepatitis C and PCT.
Choosing corticosteroids as treatment for PCT.
Ignoring hyponatraemia as a clue to AIP.
Key Examination Pearls
The easiest way to separate these conditions is:
Acute Intermittent Porphyria
Think:
Abdominal pain + neuropathy + psychiatric symptoms + no photosensitivity
Porphyria Cutanea Tarda
Think:
Photosensitive blistering skin disease + liver disease associations + iron overload
This distinction answers the majority of MRCP Part 1 questions on porphyrias.
Further MRCP Revision Resources
MRCP Part 1 Hub: https://www.crackmedicine.com/mrcp-part-1
MRCP Question Bank: https://www.crackmedicine.com/qbank
MRCP Lectures: https://www.crackmedicine.com/lectures
MRCP Mock Tests: https://www.crackmedicine.com/mock-tests
Suggested related revision topics:
Haem synthesis disorders
Iron overload syndromes
Wilson disease
Inherited metabolic disorders
Neurocutaneous diseases
FAQs
Is photosensitivity seen in Acute Intermittent Porphyria?
No. Acute Intermittent Porphyria typically presents with neurovisceral symptoms such as abdominal pain, neuropathy, and psychiatric manifestations rather than photosensitivity.
Which porphyria is associated with hepatitis C?
Porphyria Cutanea Tarda has a strong association with chronic hepatitis C infection and chronic liver disease.
Why does Acute Intermittent Porphyria cause abdominal pain?
Accumulation of haem precursors causes autonomic nervous system dysfunction, resulting in severe abdominal pain despite relatively normal physical examination findings.
What is the key diagnostic test during an acute AIP attack?
Measurement of urinary porphobilinogen is the most important diagnostic investigation during an acute attack.
Why is venesection used in Porphyria Cutanea Tarda?
Venesection reduces iron stores, which decreases porphyrin accumulation and improves skin manifestations.
Ready to start
Porphyrias are a relatively small topic within the MRCP Part 1 syllabus, but they generate highly testable questions. Focus on distinguishing neurovisceral AIP from photosensitive PCT, memorise the enzyme defects and understand the major triggers.
Continue your revision with the MRCP Part 1 overview, practise similar questions in the Free MRCP MCQs, and assess your readiness through a mock test.
Sources
MRCP(UK) Examination Blueprint and Curriculum: https://www.mrcpuk.org/mrcpuk-examinations
NHS Inform – Porphyria: https://www.nhsinform.scot/illnesses-and-conditions/blood-and-lymph/porphyria
British Society for Haematology: https://b-s-h.org.uk
European Porphyria Network: https://porphyria.eu
International Porphyria Network: https://new.porphyrianet.org
National Institute of Diabetes and Digestive and Kidney Diseases – Porphyria: https://www.niddk.nih.gov/health-information/liver-disease/porphyria
Kumar & Clark's Clinical Medicine, 11th Edition
Oxford Handbook of Clinical Medicine, 11th Edition
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