Presentation: Patient with unexplained recurrent acute abdominal pain (porphyria)

A 30-year-old woman presented to an emergency department with acute abdominal pain associated with nausea and diarrhoea which settled with opiates. A CT scan was negative as were endoscopies. She later returned with recurrent symptoms. She was noted to have tachycardia and hypertension. She appeared disorientated and had peripheral neuropathy. Blood tests show elevated alanine transaminase (ALT) 108IU/L (normal range 0–40IU/L), and hyponatraemia of 116mmol/L (normal range 133–146mmol/L). Urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) are elevated.

• A high index of suspicion for acute porphyria is desirable because the presenting findings are non-specific and can be quite variable; early diagnosis and treatment can avert long-term and life-threatening complications. First-line testing with urine porphyrins, either urinary PBG or delta-ALA, is usually increased during an acute attack.
• Genomic testing is important to confirm the diagnosis and enables detection of family members who may have a chance of developing symptoms.
• The National Genomic Test Directory outlines the following criteria for genomic testing:
  • clinical features of acute intermittent porphyria; and
  • PBG, ALA or total porphyrin testing suggests diagnosis of acute intermittent porphyria.
• Testing should be targeted at those where a genetic or genomic diagnosis will guide management for the proband or family; referrals for testing will be triaged by the genomic laboratory.
• If your patient does not meet these criteria but you have a strong clinical suspicion of an inherited cause, discuss the instance with your local Genomic Laboratory Hub (GLH).

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet containing details of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
  • To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• For investigation of possible acute intermittent porphyria, the appropriate panels are:
  • R169 Acute intermittent porphyria: This is a gene panel test covering a small number of genes that are known to cause acute intermittent porphyria.
  • R168 Non-acute porphyrias: This is a gene panel test covering a small number of genes that are known to cause non-acute porphyria (including porphyria cutanea tarda, congential erythpoietic porphyria, erythopoietic porphyria and coproporphyria).
  • R170 Variegate porphyria: This is a gene panel test covering a small number of genes that are known to cause variegate porphyria.
• The majority of genomic tests in adults are currently undertaken on a singleton basis, though samples may be needed from additional family members in order to interpret results.
• For tests which do not include whole genome sequencing, such as R169, R168 and R170, you can use your local Genomic Laboratory Hub test order and consent (record of discussion) forms.
• The majority of tests are DNA-based, and an EDTA sample (typically a purple-topped tube) is required. Exceptions include karyotype testing and DNA repair defect testing (for chromosome breakage), which require lithium heparin (typically a green-topped tube).
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• BMJ Best Practice: Acute intermittent porphyria (Symptoms, diagnosis and treatment)

Resources:

• Wang B, Bonkovsky HL, Lim JK and Balwani M. ‘AGA Clinical Practice Update on Diagnosis and Management of Acute Hepatic Porphyrias: Expert Review‘. Gastroenterology 2023: volume 164, issue 3, pages 484–491. DOI: 10.1053/j.gastro.2022.11.034

For patients

• British Liver Trust: Porphyria
• The British Porphyria Association