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Seizure 2001; 10: 64–66 doi:10.1053/seiz.2000.0473, available online at http://www.idealibrary.com on

CASE REPORT

Acute intermittent porphyria, , and antiepileptic drugs: a report on a 3-year-old Nigerian boy

R. M. SYKES

Institute of Child Health, University of Benin and University of Benin Teaching Hospital, Benin City, Nigeria

Correspondence to: R. M. Sykes, 12 Packington Square, London N1 7UF, UK

A 3-year-old Nigerian boy was treated with phenobarbitone after having a nonfebrile . Two weeks later his was found to contain , indicating that latent acute intermittent porphyria had been unmasked by phenobarbitone. The drug was discontinued and was substituted. The urine became free of porphobilinogen and the patient remained well. In developing countries phenobarbitone is the most widely used ; it must be avoided in acute intermittent porphyria, and carbamazepine may be tolerated. c 2001 BEA Trading Ltd

Key words: acute intermittent porphyria; phenobarbitone; carbamazepine.

INTRODUCTION At the return visit 2 weeks later to assess control of seizures and possible side effects of phenobarbitone, Most people with epilepsy live in developing coun- he had remained well, but his mother, who was a nurse, tries1 and the great majority receive no treatment2, 3. had noticed that his urine became dark after standing. Acute intermittent porphyria (AIP) is a rare inherited The Watson–Schwarz test for porphobilinogen (PBG) disease, and seizures are typically a manifestation of in the urine was strongly positive, and this indicated acute attacks. AIP may also coexist with idiopathic or that latent AIP had been unmasked by phenobarbitone; symptomatic epilepsy4. Since most antiepileptic drugs the drug was gradually withdrawn and carbamazepine (AEDs) may precipitate attacks of AIP in susceptible 100 mg t.d.s. was commenced. patients, a knowledge of the effects of AEDs is im- Four weeks later the Watson–Schwarz test was neg- portant. Attempts to treat seizures may unmask AIP ative. Carbamazepine was continued for 3 years and which has previously remained latent. gradually withdrawn. The boy remained well with no recurrence of seizures during a further year’s follow up, and always came near the top of his class at school. CASE REPORT There was no history suggestive of AIP in the mother’s family. The father was a surgeon working in another A 3-year-old boy was seen in the Paediatric Neurol- part of the country and was not seen at any time. ogy Clinic of the University of Benin Teaching Hospi- tal after having an unprovoked nonfebrile generalized DISCUSSION seizure. Patients with a single unprovoked seizure may benefit from treatments with AEDs5, and in Nigeria a AIP is the most common of the hepatic porphyrias and convulsing young child may be subjected to traditional results from a deficiency of the porphobilino- practices and medications with serious or even fatal re- gen deaminase. It is inherited as an autosomal dom- sults6, 7, and so it is considered prudent to attempt to inant, and symptomless and symptomatic heterozy- prevent convulsions, whether febrile or nonfebrile, in gotes have 50% deficiency of the enzyme. Approxi- this age group. Phenobarbitone was prescribed, 45 mg mately 90% of those who inherit the deficiency remain 1 (3 mg kg− ) daily. clinically unaffected throughout their lives. During a

1059–1311/01/010064 + 03 $35.00/0 c 2001 BEA Trading Ltd

Acute intermittent porphyria, seizures, and antiepileptic drugs: a report on a 3-year-old Nigerian boy 65 crisis the urine may be found to contain PBG, por- Nevertheless, the results of in vitro drug testing do phyrins and the precursor of PBG, δ-amino-laevulinic not always apply to all patients. Even drugs thought acid (ALA)8. to be unsafe are not always harmful to patients with AIP is usually latent before puberty and symptoms AIP8, as is shown by the tolerance to carbamazepine of are more frequent in females than in males. Symptoms the patient discussed here, and a similar case in a pre- may be precipitated by hormonal and nutritional fac- vious report19. Clonazepam has also been used safely, tors, and by the administration of drugs, probably by at a low dose20. inducing hepatic ALA-synthase. Amongst the drugs Concerning long-term use of AEDs for children which may do this are most AEDs8. with epilepsy and AIP, textbooks of paediatrics of- Hereditary coproporphyria is much less common fer little or no advice. Bromides are safe, but are not and less severe than AIP, but may cause difficulties likely to be tolerated. The modern treatment of choice in the management of epilepsy in childhood. Dur- is probably with or vigabatrin4, 21, which ing a crisis PBG my be found in the urine. In the are not metabolized in the . Gabapentin has been present case the faeces were not examined for co- used successfully in the treatment of two patients with proporphyrins, so this diagnosis remains a remote seizures and AIP22. possibility9. These newer and safe AEDs are not likely to be is almost always present during a available in developing countries, where phenobar- crisis in AIP. Seizures are not infrequent and hyperten- bitone is the most widely used drug for epilepsy23, sion and hyponatraemia may be factors. Inappropriate largely because of its cheapness. Carbamazepine, secretion of antidiuretic hormone may be responsible though more costly, is available in several countries23, for hyponatraemia. and has been found to be effective in intractable AIP has been described in West Africa; 1 out of epilepsy in children in Nigeria24. It is encouraging to 3 patients who presented with abdominal pain had know that it may be used, with due consideration and seizures10. when indicated, in AIP. Monitoring of the urine for Seizures may be the presenting symptom of AIP in PBG is recommended. childhood or adult life, in which case the administra- tion of AEDs may have disastrous consequences. A man who was thought to have idiopathic seizures was treated with ; when his condition worsened REFERENCES treatment was changed to sodium , but dete- rioration continued. 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