A CASE OF ALAD PORPHYRIA IN NORTH AMERICA: RESPONSE TO HEMIN THERAPY

1Chul Lee, 1Karl E. Anderson, 2Shigeru Sassa and 3Reiko Akagi

 

1The University of Texas Medical Branch, Galveston, Texas, USA; 2Rockefeller University, New York, USA; 3Okayama Prefectural University, Okayama-ken, Japan

 

 

Porphyria due to 5-aminolevulinic acid (ALA) dehydratase (ALAD) deficiency is termed ALAD porphyria (ADP) and was first described by Doss in 1979.  Of ~7 cases described five have been documented at the molecular level.  ADP is classified as one of four acute hepatic porphyrias, although the finding of increased erythrocyte zinc protoporphyrin suggests a disturbance of heme biosynthesis in bone marrow erythroblasts as well.  Treatment with intravenous hemin is widely recommended, but a biochemical response has been documented in only two cases (Gross et al 1998).  There is a need for further study of therapy in this very rare form of human porphyria. 

Here we describe the clinical features and response to hemin therapy a 14 year old boy who presented with abdominal pain, tachycardia, hypertension and low grade fever.  ADP was suggested by markedly increased excretion of urinary ALA and total porphyrins (mostly coproporphyrin III) and erythrocyte zinc protoporphyrin, without significant increases in urinary porphobilinogen and fecal porphyins.  Plasma ALA (Lee et al 2004) was also markedly elevated.  Erythrocyte ALAD activity was <8% of normal, and approximately half-normal in both parents and a brother.  Two novel ALAD mutations, one inherited from each parent, were documented and studied in detail (Kato et al, submitted).  There was no response to intravenous glucose after one day.  Administration of lyophilized hemin (Panhematin®, Ovation) 3 mg/kg body weight reconstituted with human albumin once daily for 4 days resulted in rapid decreases in urinary and plasma ALA.  There was also rapid clinical improvement, and he was discharged 2 days after the course of treatment was completed.  Two attacks developed during the next year, and one was treated with hemin.  These findings support the early use of intravenous hemin for treatment of attacks of ADP.