Directorate of Laboratory Medicine Blood Sciences Page 1 of 7 BS-CTG-Biochem-25 Revision Version: 1

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1 Blood Sciences Page 1 of 7 BS-CTG-Biochem-25 Revision Version: 1 SELECTING TESTS FOR THE INVESTIGATION OF THE PORPHYRIAS 1. INTRODUCTION The s are a group of disorders of haem synthesis that can present with acute neurovisceral attacks or cutaneous symptoms on exposure of skin to the sun (and in some disorders both). Acute attacks are associated with severe abdominal pain, nausea, vomiting, autonomic disturbance and peripheral motor neuropathy. Cutaneous s can be acute or chronic Acute Porphyrias There are 4 disorders that can present with acute neurovisceral attacks: Acute intermittent (AIP) Variegate (VP)* Hereditary copro (HCP)* Aminolevulinic acid dehydratase (ADP) *May also be associated with cutaneous symptoms ADP is an exceedingly rare autosomal recessive disease and not associated with raised urine PBG, only ALA. Acute attacks are related to the presence of precipitating factors which may include drugs, alcohol, infection, reduced calorie intake, stress and hormonal factors. The only specific treatment available is to provide the end product of the haem biosynthetic pathway as intravenous haem arginate. Treatment may be more effective if given early. Unfortunately, diagnostic delay is common. There is a National Porphyria Service (NAPS) that provides 24hr access to expert advice on treatment of acute attacks and follow-up: National Acute Porphyria Service (NAPS) Tel: (University Hospital of Wales Switchboard)

2 Blood Sciences Page 2 of 7 BS-CTG-Biochem-25 Revision Version: Cutaneous Porphyrias Cutaneous s present with two distinct patterns of photosensitivity. There are those that are associated with chronic skin fragility and blisters in sun exposed areas: Porphyria cutanea tarda (PCT) Variagate (VP)* Hereditary copro (HCP)* Congenital erythropoietic (CEP) *Also associated with acute neurovisceral attacks The fifth cutaneous is erythropoietic proto (EPP), which is associated with acute pain after only a few minutes of sun exposure. 2. DIAGNOSTIC APPROACH The diagnostic approach varies depending on the symptoms/signs and the (s) suspected. The chart below details the four situations that may occur and which flow chart in this document to follow. Request for urine PBG/urine porphyrins/plasma porphyrins/faecal porhpyrins Check clinical background Current symptoms of acute attack -?acute?acute (no current symptoms of acute attack)?cutaneous (skin lesions/ photosensitivity) Monitoring of known Flow chart 1 Flow chart 2 Flow chart 3 Flow chart 4

3 Blood Sciences Page 3 of 7 BS-CTG-Biochem-25 Revision Version: 1 In each situation it is important that the appropriate samples are taken and either analysed in-house (in the case of PBG) or referred to the specialist laboratory in Cardiff. 2.1 Current symptoms of acute attack FLOW CHART 1 Current symptoms of acute attack -?acute Random Urine, EDTA whole blood, faeces (protected Measure urine PBG (NUTH) PBG -ve PBG +ve or ongoing strong clinical suspicion of acute Acute attack of excluded as cause of current symptoms Original urine + EDTA whole blood + faeces With full clinical details and local PBG result Store urine, whole blood and faeces An acute neurovisceral attack is a medical emergency and PBG analysis should be performed urgently where it is suspected (same day). PBG analysis is performed inhouse and should not be referred to Cardiff.

4 Blood Sciences Page 4 of 7 BS-CTG-Biochem-25 Revision Version: 1 A negative PBG (result within the reference range) means that an acute attack of is effectively excluded as a cause of current symptoms. Further biochemical investigation is only necessary if there is strong ongoing suspicion of (e.g. family history of ). Note that very dilute urine (<2 mml/l creatinine) may lead to false negative PBG results. If PBG is positive (above the upper limit of the reference range) or there is strong ongoing clinical suspicion, then urine, EDTA whole blood and faeces samples should be referred to Cardiff for analysis in order to confirm and determine the type of. The request must be sent with full clinical details to guide further analysis in Cardiff and also the local PBG result (repeat PBG measurement in Cardiff is not required). If samples for Cardiff porphyrin analysis are being held, pending local PBG result, pass the referral forms onto the next Duty Biochemist so that the referral can be reviewed once the local PBG result is available. 2.2.?Acute no current symptoms of acute attack FLOW CHART 2?Acute (no current symptoms of acute attack) Random Urine, EDTA whole blood, faeces (protected Measure urine PBG (NUTH) Original urine + EDTA whole blood + faeces With full clinical details and local PBG result

5 Blood Sciences Page 5 of 7 BS-CTG-Biochem-25 Revision Version: 1 Where acute is suspected but the patient is not currently experiencing an acute attack, it is important that both PBG is measured (in-house) and urine, whole blood and faeces samples are sent to Cardiff for further analysis as PBG is not always raised between acute attacks (although usually is for AIP). 2.3?Cutaneous (skin lesions/acute photosensitivity) FLOW CHART 3?Cutaneous (skin lesions/ photosensitivity) Bullous skin lesions Acute photosensitivity Random Urine, EDTA whole blood, faeces (protected With full clinical details EDTA whole blood (protected With full clinical details In cases of suspected cutaneous, PBG analysis is not required. The appropriate samples should be referred to Cardiff with relevant clinical details (urine, blood and faeces in cases of skin lesions and blood only for acute photosensitivity).

6 Blood Sciences Page 6 of 7 BS-CTG-Biochem-25 Revision Version: Monitoring of known FLOW CHART 4 Monitoring of known Acute intermittent (AIP) Variagate / hereditary copro (VP/ HCP) Porphyria cutanea tarda (PCT) Erythropoietic proroporhpyria (EPP) Random urine (protected Random urine (protected Random urine (protected EDTA whole blood (protected Urine PBG (NUTH) Urine PBG (NUTH) (for urine total porphyrin only) (for urine total porphyrin only) (for total RBC protoporphyrin) The relevant tests for monitoring purposes depend on the type of that the patient has. Only the tests stipulated in Flow Chart 4 should be performed. Relevant clinical details should be sent to Cardiff and the precise test required should be noted (e.g. monitoring known EPP, total RBC protoporphyrin only) Summary Following this guide should ensure that the appropriate samples are submitted for the required tests in these different situations. Ensuring that all of the appropriate samples are received and that we have relevant clinical details may require discussion with the requesting clinicians. A summary of the laboratory findings in the various s can be found in the table below.

7 Blood Sciences Page 7 of 7 BS-CTG-Biochem-25 Revision Version: 1 Disorder Urine Faeces Plasma Erythrocytes ACUTE ADP AIP ALA, coproporphyrin ALA, PBG, uroporphyrin VP ALA, PBG*, coproporphyrin III HCP ALA, PBG*, coproporphyrin III NON-ACUTE PCT Uroporphyrin, heptacarboxylic porphyrin CEP Uroporphyrin, coproporphyrin I EPP NAD Protoporphyrin in 40% NAD NAD Zn protoporphyrin NAD or slight nm NAD increase of normal profile Proto>copro III nm NAD Coproporphyrin III nm NAD *PBG may not be elevated between acute attacks in VP and HCP Isocoproporphyrin, heptacarboxylic porphyrin nm NAD Coproporphyrin I nm Zn and free protoporphyrin nm Free protoporphhyrin 4.0. REFERENCES 4.1. Woolf J, Marsden J, Degg T, Whatley S, Reed P, Brazil N, Stewart M, Badminton M. Best practice guidelines on first line laboratory testing for. Annals of Clinical Biochemistry Accepted 2016 DOI: / Zaider E, Bickers D. Clinical laboratory methods for diagnosis of the s. Clinics in Dermatology 1998:16; Deacon A, Elder G. Front line tests for the investigation of suspected. Journal of Clinical Pathology 2001:54;