Circulating fluorocytes at the first attack of acute intermittent porphyria: a missing link in the pathogenesis.
BACKGROUND
Acute intermittent porphyria (AIP) is an autosomal dominant disorder of the haem biosynthesis resulting from a partial deficiency of hydroxymethylbilane synthase (HMBS) with incomplete penetrance. By conventional means, it is able to identify asymptomatic mutation carrier by molecular diagnosis, but one cannot reliably predict an acute porphyric attack. The presence of fluorescent red cells (fluorocytes) in AIP is probably under-recognized since AIP is a hepatic porphyria and not associated with photosensitivity.


METHODS
We used an automatic image acquisition platform to detect the circulating fluorocytes at 700 nm emission in a diabetic AIP patient during acute attack. We screened the patient and her family members for the mutation on HMBS, urine porphobilinogen and circulating fluorocytes.


RESULTS
The patient was heterozygous for a disease-causing mutation on HMBS and several bright circulating fluorocytes were detected. We showed evidence that protoporphyrin contributed to the erythrocyte auto-fluorescence. Interestingly, asymptomatic mutation carriers with increased urine porphobilinogen did not have circulating fluorocytes. All mutation-negative family members revealed no circulating fluorocytes.


CONCLUSIONS
Sudden decrease in plasma glucose concentration might invoke acute attack of AIP and appearance of circulatory fluorocytes. Potential of detecting fluorocytes as screening test or for predicting an acute attack of AIP in diabetes is worth investigating.
Lam
Ching-Wan
CW
Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China. ching-wanlam@pathology.hku.hk
Lau
Kin-Chong
KC
Mak
Chloe Miu
CM
Tsang
Man-Wo
MW
Chan
Yan-Wo
YW
D000328:Adult; D004252:DNA Mutational Analysis; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism*; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000235:genetics; D057054:Molecular Imaging; D017118:Porphyria, Acute Intermittent / Q000097:blood* / Q000201:enzymology / Q000235:genetics / Q000473:pathology*
D005456:Fluorescent Dyes; D011163:Hydroxymethylbilane Synthase