Porphyria recurrence in a transplant recipient illustrates the need for genetic screening of related organ donors

1. A patient with acute intermittent porphyria received a liver transplant from a brother which was expected to be curative, but her symptoms recurred.

2. The brother had the same dominant porphyria-associated mutation as the patient, though he was asymptomatic and had not been offered genetic testing before the transplant.

Evidence Rating Level: 4 (Below average)          

Study Rundown: Acute intermittent porphyria (AIP) is a rare autosomal dominant disorder of hemoglobin metabolism that is managed with frequent hemin infusions.  Though patients receive concomitant chelation therapy, many develop symptomatic hepatic iron overload and some ultimately require liver transplant.  In this case report, a 59-year-old woman with AIP received a liver transplant with tissue from her brother.  Though transplant was expected to be curative for both her liver failure and porphyria, the patient started having recurrent attacks of acute porphyria four years after her transplant.  Genetic testing revealed that her brother had the same mutated version of the porphobilogen deaminae gene (PBGD/HMBS), though he has never had symptoms of porphyria, suggesting that the donated organ may have been affected.  At present, genetic testing of sibling liver donors is not standard practice, even for autosomal conditions like AIP.  This case supported incorporation of targeted testing for hereditary diseases, to guard against symptom recurrence.  However, these results are only relevant for diseases with low penetrance, where it is plausible that the organ donor might carry the affected allele without symptoms.

Click to read the study in Annals of Internal Medicine

Relevant Reading: Liver transplantation in the management of porphyria

In-Depth [case report]: This report describes the clinical course of a 59-year-old woman with AIP.  She was first diagnosed with AIP at 23, and her symptoms progressed over the next two decades until she became reliant upon weekly hemin infusions.  Despite chelation therapy, she developed symptomatic hepatic iron overload and decompensated cirrhosis.  Since she didn’t meet criteria for a deceased donor transplant, her brother provided tissue instead.  She was asymptomatic for four years after the transplant, at which point she started having episodes of nausea, vomiting, abdominal pain, and confusion.  Biochemical testing showed elevated urinary porphobilinogen and aminolevulinic acid, confirming the diagnosis of recurrent porphyria.  Since the transplant was expected to cure the patient’s porphyria, the patient’s brother (and organ donor) underwent genetic testing.  He was found to carry the same mutation in the PBGD/HMBS gene as his sister, implying that the patient likely received a porphyric liver.

Image: PD

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