Porphyria

A metabolic disorder - or rather a group of disorders - that result from improper breakdown of haem. The same pigment that makes blood red causes problems if not dealt with completely by the body. Some sufferers have skin problems, especially after exposure to light which seems to sensitize the skin. More dangerous is an acute attack - vomiting, constipation and even mental disturbances like depression, hallucinations or schizophrenia. Attacks can be brought on by diet, certain pharmaceuticals and alcohol.

Interestingly, George The Third may have been a sufferer. His behaviour under the influence of severe attacks, combined with symptoms such as the colour of his stools suggests porphyria. Since certain types of porphyria are inherited, the disease can be traced through the royal family (in much the same way as haemophillia was).

Culled from various internet sources, and a play I saw once.

Some have suggested Porphyria as being the origin of the ancient legends of vampirism. Among the manifestations caused by the resulting anemia are pale skin, red eye discolourations, retracted gingiva and increased sensitivity towards sunlight. Some have even claimed that the anemia might present as an extreme thirst for blood, although I doubt that medical evidence for this is very supportive.

Acute Intermittent Porphyria (AIP):

AIP is non-gender specific hereditary. People with AIP are at risk of developing an acute attack. With AIP, unlike other forms of porphyria, the skin will not be affected.

Variegate Porphyria (VP) and Hereditary Coproporphyria (HC):

Like AIP, VP and HC are hereditary and acute attacks are a possibility, unlike AIP patients tend to have skin problems.

Plumboporphyria (PP):

PP is an extremely rare version of an extremely rare condition. In the few known cases, it has been seen to be very similar to AIP.

Porphyria Cutanea Tarda (PCT):

This form of porphyria can be inherited, but this is rare. It is a condition that may because of excessive alcohol ingestion. Other causes are the contraceptive pill and other non-natural oestrogen sources. PCT sufferers will have skin problems, but no acute attacks. Also, the unsafe drugs list is inapplicable, although patients should avoid alcohol.

Erthyropoeitic Protoporphyria (EPP):

Also rare, this form is hereditary. Skin problems may be an issue, but the unsafe drugs are not.

Congenital Porphyria (CP)

This is the rarest of the porphyria. It is primarily a skin condition. Both parents need to have porphyria.

The acute attack

When the levels of the porphyrin get too high an acute attack occurs. Symptoms include:

• abdominal pain
• cramps
• constipation
• nausea
• vomiting
• anxiety
• depression
• paralysis
• death
• hypertension
• increased photosensitivity
• Nerve damage (esp on the back causing excrutiating back pain requiring morphine)

Skin problems

Problems include ice-pick scabs and blisters. The skin is generally weak and so is easily scraped off. This problem is heightened with exposure to sunlight.

Unsafe Drugs

Bracketed drugs are those in which there is conflicting experimental evidence of porphyrinogenicity - some positive, - some negative

* Those marked with an asterisk have been associated with acute attacks of porphyria.

A:

ALCURONIUM

*ALPHAXALONE: ALPHADOLONE

ALPRAZOLAM

ALUMINIUM PREPARATIONS

AMIDOPYRINE

AMINOGLUTETHIMIDE

AMINOPHYLLINE

AMIODARONE

*AMITRIPTYLINE

(AMPHETAMINES)

*AMYLOBARBITONE

ANTIPYRINE

*AURANOFIN

*AUROTHIOMALATE

AZAPROPAZONE

B:

BACLOFEN

*BARBITURATES

*BEMEGRIDE

BENDROFLUAZIDE

BENOXAPROFEN

BENZBROMARONE

(BENZYLTHIOURACIL)

(BEPRIDIL)

BROMOCRIPTINE

BUSULPHAN

*BUTYLSCOPOLAMINE

C:

CAPTOPRIL

*CARBAMAZEPINE

*CARBROMAL

*CARISOPRODOL

(CEFUROXIME)

(CEPHALEXIN)

(CEPHALOSPORINS)

(CEPHRADINE)

(CHLORAMBUCIL)

*CHLORAMPHENICOL

*CHLORDIAZEPOXIDE

*CHLORMEZANONE

CHLOROFORM

*CHLORPROPAMIDE

CIMETIDINE

CINNARIZINE

CLEMASTINE

(CLOBAZAM)

(CLOMIPRAMINE HCl)

(CLONAZEPAM)

CLONIDINE HCL

*CLORAZEPATE

COCAINE

(COLISTIN)

CO-TRIMOXAZOLE

CYCLOPHOSPHAMIDE

CYCLOSERINE

CYCLOSPORIN

D:

DANAZOL

*DAPSONE

DEXFENFLURAMINE

DEXTROPROPOXYPHENE

DIAZEPAM

*DICHLORALPHENAZONE

*DICLOFENAC Na

DIENOESTROL

DIETHYLPROPION

DIHYDRALAZINE

*DIHYDROERGOTAMINE

DILTIAZEM

*DIMENHYDRINATE

*DIPHENHYDRAMINE

(DOTHIEPIN HCl)

DOXYCYCLINE

*DYDROGESTERONE)

E:

*ECONAZOLE NO3

*ENALAPRIL

ENFLURANE

*ERGOT COMPOUNDS

ERGOMETRINE MALEATE

ERGOTAMINE TARTRATE

*ERYTHROMYCIN

*ESTRAMUSTINE

ETHAMSYLATE

*ETHANOL

ETHIONAMIDE

*ETHOSUXIMIDE

*ETHOTOIN

ETIDOCAINE

ETOMIDATE

F:

FENFLURAMINE

*FLUCLOXACILLIN

*FLUFENAMIC ACID

FLUNITRAZEPAM

FLUPENTHIXOL

FLURAZEPAM

*FRUSEMIDE

G:

*GLIBENCLAMIDE

*GLUTETHIMIDE

*GLIPIZIDE

GRAMICIDIN

*GRISEOFULVIN

H:

(HALOPERIDOL)

*HALOTHANE

*HYDANTOINS

*HYDRALAZINE

*HYDROCHLOROTHIAZIDE

*HYDROXYZINE

HYOSCINE

I:

*IMIPRAMINE

IPRONIAZID

ISOMETHEPTENE MUCATE

(ISONIAZID)

K:

KEBUZONE

KETOCONAZOLE

L:

*LEVONORGESTROL

LIGNOCAINE

*LISINOPRIL

LOPRAZOLAM

LOXAPINE

*LYNESTRENOL

LYSURIDE MALEATE

M:

MAPROTILINE HCl

MEBEVERINE HCl

*MECILLINAM

*MEDROXYPROGESTERONE

(MEFENAMIC ACID)

MEGESTROL ACETATE

*MEPHENYTOIN

MEPIVACAINE

*MEPROBAMATE

MERCAPTOPURINE

MERCURY COMPOUNDS

MESTRANOL

(METAPRAMINE HCl)

METHAMPHETAMINE

METHOHEXITONE

METHOTREXATE

METHOXYFLURANE

METHSUXIMIDE

*METHYL DOPA

*METHYL SULPHONAL

*METHYPRYLONE

METHYSERGIDE

*METOCLOPRAMIDE

METYRAPONE

MIANSERIN HCl

MICONAZOLE

(MIFEPRISTONE)

MINOXIDIL

N:

*NADROLONE

*NALIDIXIC ACID

NATAMYCIN

*NANDROLONE

(NICERGOLINE)

*NIFEDIPINE

*NIKETHAMIDE

NITRAZEPAM

*NITROFURANTOIN

NORDAZEPAM

NORETHYNODREL

*NORETHISTERONE

(NORTRIPTYLINE)

NOVOBIOCIN

O:

*ORAL CONTRACEPTIVES

*ORPHENADRINE

OXANAMIDE

(OXAZEPAM)

OXYBUTYNIN HCl

OXYCODONE

*OXYMETAZOLINE

*OXYPHENBUTAZONE

OXYTETRACYCLINE

P:

PARAMETHADIONE

PARGYLINE

*PENTAZOCINE

PERHEXILINE

PHENACETIN

PHENELZINE

*PHENOBARBITONE

PHENOXYBENZAMINE

*PHENSUXIMIDE

*PHENYLBUTAZONE

PHENYLHYDRAZINE

*PHENYTOIN

PIPEBUZONE

PIPEMIDIC ACID

PIRITRAMIDE

*PIROXICAM

*PIVAMPICILLIN

*PIVMECILLINAM

PRAZEPAM

PRENYLAMINE

*PRILOCAINE

*PRIMIDONE

(PROBENECID)

*PROGESTERONE

PROGABIDE

PROMETHAZINE

(PROPANIDID)

*PYRAZINAMIDE

PYRROCAINE

Q:

QUINALBARBITONE

R:

RIFAMPICIN

S:

SIMVASTATIN

SODIUM AUROTHIOMALATE

SODIUM OXYBATE

(SODIUM VALPROATE)

*SPIRONOLACTONE

STANOZOLOL

SUCCINIMIDES

*SULPHACETAMIDE

*SULPHADIAZINE

*SULPHADIMIDINE

*SULPHADOXINE

*SULPHAMETHOXAZOLE

*SULPHASALAZINE

*SULPHONYLUREAS

SULPHINPYRAZONE

SULPIRIDE

SULTHIAME

SULTOPRIDE

T:

*TAMOXIFEN

*TERFENADINE

TETRAZEPAM

*THEOPHYLLINE

*THIOPENTONE Na

THIORIDAZINE

TILIDATE

TINIDAZOLE

*TOLAZAMIDE

*TOLBUTAMIDE

TRANYLCYPROMINE

TRAZODONE HCl

TRIMETHOPRIM

(TRIMIPRAMINE)

TROXIDONE

V:

VALPROATE

VALPROMIDE

VERALIPRIDE

*VERAPAMIL

*VIBRAMYCIN

VILOXAZINE HCl

(VINBLASTINE)

(VINCRISTINE)

Z:

ZUCLOPENTHIXOL

SAFE DRUGS

A:

ACETAZOLAMIDE

ACETYLCHOLINE

ACTINOMYCIN D

ACYCLOVIR

ADENOSINE MONOPHOSPHATE

ADRENALINE

ALCLOFENAC

ALLOPURINOL

ALPHA TOCOPHERYL ACETATE

AMETHOCAINE

AMILORIDE

AMINOCAPROIC ACID

AMINOGLYCOSIDES

AMOXYCILLIN

AMPHOTERICIN

AMPICILLIN

ASCORBIC ACID

ASPIRIN

ATENOLOL

ATROPINE

AZATHIOPRINE

B:

BECLOMETHASONE

BENZHEXOL HCl

BETA-CAROTENE

BIGUANIDES

(BROMAZEPAM)

BROMIDES

BUFLOMEDIL HCl

BUMETANIDE

BUPIVACAINE

BUPRENORPHINE

BUSERELIN

BUTACAINE SO4

C:

CANTHAXANTHIN

CARBIMAZOLE

(CARPIPRAMINE HCl)

CHLORAL HYDRATE

(CHLORMETHIAZOLE)

(CHLOROQUINE)

(CHLOROTHIAZIDE)

CHLORPHENIRAMINE

CHLORPROMAZINE

CIPROFLOXACIN

CISAPRIDE

CISPLATIN

CLAVULANIC ACID

CLOFIBRATE

CLOMIPHENE

CLOXACILLIN

CO-CODAMOL

CODEINE PHOSPHATE

COLCHICINE

(CORTICOSTEROIDS)

CORTICOTROPHIN (ACTH)

COUMARINS

CYCLIZINE

CYCLOPENTHIAZIDE

CYCLOPROPANE

(CYPROTERONE ACETATE)

D:

DANTHRON

DESFERRIOXAMINE

DEXAMETHASONE

(DEXTROMORAMIDE)

DEXTROSE

DIAMORPHINE

DIAZOXIDE

DICYCLOMINE HCl

DIFLUNISAL

DIGOXIN

DIHYDROCODEINE

DIMERCAPROL

DIMETHICONE

DINOPROST

DIPHENOXYLATE HCl

DIPYRIDAMOLE

(DISOPYRAMIDE)

DOMPERIDONE

DOXORUBICIN HCl

DROPERIDOL

E:

(ESTAZOLAM)

ETHACRYNIC ACID

ETHAMBUTOL

(ETHINYL OESTRADIOL)

ETHOHEPTAZINE CITRATE

ETOPOSIDE

F:

FAMOTIDINE

FENBRUFEN

(FENOFIBRATE)

FENOPROFEN

FENTANYL

FLUCYTOSINE

FLUMAZENIL

FLUOXETINE HCl

FLURBIPROFEN

FLUVOXAMINE MALEATE

FOLIC ACID

FRUCTOSE

FUSIDIC ACID

F.S.H.

G:

GENTAMICIN

GLAFENINE

GLUCAGON

GLUCOSE

GLYCERYL TRINITRATE

GOSERELIN

GUANETHIDINE

GUANFACINE HCl

H:

HAEM ARGINATE

(HALOPERIDOL)

HEPARIN

HEPTAMINOL HCl

HEXAMINE

(HYDROCORTISONE)

I:

IBUPROFEN

INDOMETHACIN

INSULIN

IRON

J:

JOSAMYCIN

K:

(KETAMINE)

KETOPROFEN

KETOTIFEN

L:

LABETALOL

L.H.R.H.

LIQUORICE

LITHIUM SALTS

LOFEPRAMINE

LOPERAMIDE

(LORAZEPAM)

M:

MAGNESIUM-SULPHATE

(MEBENDAZOLE)

MECAMYLAMINE

MECLOFENOXATE HCl

MECLOZINE

MEFLOQUINE HCl

(MELPHALAN)

MEPTAZINOL

MEQUITAZINE

METFORMIN

METHADONE

(METHOTRIMEPRAZINE)

METHYLPHENIDATE

METHYLURACIL

METIPROPRANOLOL

METOPIMAZINE

METOPROLOL

(METRONIDAZOLE)

(MIDAZOLAM)

MINAPRINE HCl

MINAXOLONE

MORPHINE

N:

NADOLOL

NAFTIDROFURYL OXALATE

(NAPROXEN SODIUM)

NATAMYCIN

NEFOPAM HCl

NEOSTIGMINE

NETILMICIN

NIFLUMIC ACID

NITROUS OXIDE

NORFLOXACIN

O:

OFLOXACIN

OXOLINIC ACID

OXYBUPROCAINE

(OXYPHENBUTAZONE)

OXYTOCIN

P:

(PANCURONIUM BROMIDE)

PARACETAMOL

PARALDEHYDE

PARAPENZOLATE Br

PENICILLAMINE

PENICILLIN

PENTOLINIUM

PERICYAZINE

PETHIDINE

PHENFORMIN

PHENOPERIDINE

PHENTOLAMINE MESYLATE

PIPOTHIAZINE PALMITATE

PIRACETAM

PIRBUTEROL

PIRENZEPINE

PIZOTIFEN

(PRAZOSIN)

(PREDNISOLONE)

PRIMAQUINE

PROBUCOL

PROCAINAMIDE HCl

PROCAINE

PROCHLORPERAZINE

PROGUANIL HCl

PROMAZINE

PROPANTHELINE Br

PROPOFOL

PROPRANOLOL

PROPYLTHIOURACIL

(PROXYMETACAINE)

PSEUDOEPHEDRINE HCl

PYRIDOXINE

(PYRIMETHAMINE)

Q:

QUINIDINE

QUININE

R:

(RANITIDINE)

RESERPINE

RESORCINOL

S:

SALBUTAMOL

SENNA

SODIUM BROMIDE

SODIUM Ca EDTA

SODIUM FUSIDATE

SORBITOL

STREPTOMYCIN

SULBUTIAMINE

SULINDAC

SULFADOXINE

SUXAMETHONIUM

T:

TALAMPICILLIN

TEMAZEPAM

TETRACAINE

(TETRACYCLINES)

THIOURACILS

THYROXINE

TIAPROFENIC ACID

TICARCILLIN

TIENILIC ACID

TIMOLOL MALEATE

TOLAZOLINE

TRANEXAMIC ACID

TRIACETYLOLEANDOMYCIN

TRIAMTERENE

TRIAZOLAM

(TRICHLORMETHIAZIDE)

TRIFLUOPERAZINE

TRIMEPRAZINE TARTRATE

TRIMETAZIDINE HCl

TRIPELENNAMINE

TUBOCURARINE

V:

VANCOMYCIN

(VINCRISTINE)

VITAMINS

W:

WARFARIN SODIUM

Z:

ZIDOVUDINE

ZINC PREPARATIONS (TOPICAL)

Source: Michael R. Moore, Porphyria Research Unit, The University Of Queensland, NRCET, Department Of Medicine 1999

This was adapted from a report I wrote as a final exam for my genetics class.

Porphyrias are a group of diseases which are all deficiencies of any of the eight enzymes involved in heme synthesis. One of the major causes of symptoms in patients with porphyria is the accumulation of heme precursors. To make heme, the body needs some raw materials in addition to the eight enzymes. Heme procursors collect mainly in the marrow and liver. The main heme precursors that cause problems in porphyria are toxic metabolites: delta-aminolevulinic acid and porphobilinogen, which are neurotoxins, and porphyrins. These precursors are transferred from the tissues where they accumulate into the blood plasma and from there they are excreted in urine and stools. Accumulation of these precursors can cause photosensitivity and nerve damage, even paralysis.

The most common porphyrias are porphyria cutanea tarda (PCT), acute intermittent porphyria, and eryhtropoietic protoporphyria. These are very different diseases, with distinct symptoms, tests needed for proper diagnosis, and treatments. Additionally, they all share some symptoms with rarer porphyrias. Thus, porphyria is often misdiagnosed. Test results from patients with porphyria will be markedly abnormal, but one needs to select and interpret tests with porphyria in mind.

All porphyrias except for one are hereditary. PCT is not inherited directly. However, suspectibility to PCT is often inherited, in which case it is called familial (type II) PCT.

There are several systems for classifying porphyria. The preferred system is to classify by specific enzyme deficiency. Deficiencies of different enzymes are responsible for different porphyrias. There is also a system which breaks porphyrias down into acute porphyrias, which manifest themselves primarily via neurologic symptoms, and cutaneous porphyrias, which cause photosensitivity. In addition, there is a third system which splits up the diseases into hepatic porphyrias, where the heme precursors originate in the liver, and erythropoietic porphyrias, where they originiate in the marrow.

See my Porphyria Cutanea Tarda writeup for bibliography.