VARIEGATE PORPHYRIA VERSUS PCT AND ACNE: PITFALLS IN DIAGNOSIS AND TREATMENT
Th. Stauch, M. Doss-Frank and M. O. Doss
German Competence Center for Porphyria Diagnosis and Consultation, Marburg and Karlsruhe, Germany (www.porphyrie.com)
Porphyria cutanea tarda (PCT) was diagnosed in a case of a 44 year old woman with acne conglobata since 20 years, initiated as acne fulminans together with light in-duced cutaneous symptoms (mainly blisters) since 4 years. The PCT-diagnosis was made on basis of histologic examination of a skin biopsy and a mild increase of uri-nary uroporphyrin within a slightly elevated excretion of total porphyrins (168 µg/die).
Treatment with chloroquine was initiated. The patient mentioned periods of abdominal pain about 10 years ago.
The examinations in our laboratory revealed the following data: Moderate elevation of d-aminolevulinic acid and porphobilinogen and an excessive porphyrin excretion (3223 µg/l, normal: <145) with dominance of coproporphyrin (70%) and an increase of isomer III (91%, normal: 69-83). Fecal porphyrins were increased up to 440 µg/g (normal: <85) mainly due to an elevated excretion of protoporphyrin. An inversion of faecal coproporphyrin isomers could be observed ( 62% isomer III, normal: 23-35). The activity of porphobilinogen desaminase was found normal. Therefore the diagno-sis of a variegate porphyria (VP) in a non-acute phase was established. Family studies showed normal urinary porphyrin precursors and porphyrin excretion in mother and son (15 years). The faecal porphyrin excretion of the mother was 25 µg/g. Even lower were the stool porphyrins of the son (<10 µg/g) stating no metabolic indication of a genetic protoporphyrinogen oxidase defect in both cases. The father of the patient is deceased, so there is no sample material available.
Sequence analysis of the protoporphyrinogen oxidase gene revealed a mutation(base exchange) in exon 9 leading to an exchange of leucin for prolin (L291P).
To our knowledge this mutation was not described so far as being responsible for an enzyme deficiency, but the short distance of the location to a known and significant base exchange (only 4 base pairs) suggests that this mutation can assumed to be responsible for the lack of enzyme activity leading to the discribed metabolic disorder.
Molecular genetic studies considering the other members of the family are in progress.
Conclusion: The determination of urinary and faecal porphyrin excretion patterns gave evidence for variegate porphyria (VP). The metabolic constellation found in the patient is characterstic for this type of acute hepatic porphyria. The preceding diagnosis of PCT could be ruled out. As a consequence the chloroquine therapy was suspended.
In Germany VP is the second frequent acute hepatic porphyria; 102 cases (62 males and 40 females) were diagnosed during 40 years of activity in the Marburg porphyria center. This case shows that histopathologic examinations of skin samples together with the clinical/dermatological aspect can lead to a presumption of a disorder in the porphyrin metabolism, but they are not at all sufficient in establishing the final diagno-sis or classification of the metabolic disease.