P3883 - Identification of a Novel Mutation in Porphyria Cutanea Tarda

Ahmed Elhawary, MD¹, Kymberly Watt, MD¹, Ummah Salma Nisar, MD², Mounika Angirekula, MD^3
1Mayo Clinic, Rochester, MN; ²Mayo Clinic, Knoxville, TN; ³Mayo Clinic, Elkridge, MD

Introduction: Porphyria cutanea tarda (PCT) is characterized by deposition of porphyrin in the skin, liver and blood vessels and manifests as skin blistering on exposure to light.




Type 2 PCT is due to familial heterozygous UROD mutations with nearly 50 percent decreased UROD levels in all cells including fibroblasts, red blood cells and liver.

Case Description/Methods: A 42-year-old male with episodes of blisters on the dorsum of both hands and skin fragility for 6 months. He drinks 1-2 alcohol beverages every 1-2 weeks except on vacations. He denies any use of medications, supplements, and herbal products. His father also develops blisters on his hands following sun exposure.




Physical examination showed multiple erosions on the dorsum of both hands and white minute papules consistent with milia.
Hemochromatosis gene analysis revealed heterozygote H63D mutation but no C282Y mutation. Transient elastography showed no significant fibrosis and grade 1 steatosis. The liver biopsy showed mild nonspecific portal inflammation, minimal steatosis, minimal sinusoidal fibrosis, and trace iron deposition within hepatocytes and Kupffer cells.




UROD gene analysis for this patient revealed c.812_842del, p.Glu271Glyfs*19 alteration which results in frame shift and premature termination of the UROD protein. This variant has not been previously reported but is expected to be pathogenic. Exome hybridization probe was used to capture coding regions of targeted genes plus 10 bases of non-coding DNA flanking region for every exon and regions of interest sequenced using Illumina’s Nova Seq 6000 using 150 by 150 bp paired end reads.




Based on molecular analyses, the patient was recommended to discontinue the alcohol intake and utilize sun protection. Patient preference was for phlebotomy. After 6 months his skin lesions had completely resolved, and his liver tests normalized.

Discussion: PCT manifests in the late adulthood with cutaneous symptoms, symptoms from iron overload and liver test abnormalities. The common clinical presentation is photosensitivity, formation of blisters, skin fragility on the sun exposure and with minor trauma. PCT is manifested when liver cell injury is triggered by precipitating factors such as alcohol, iron overload, estrogen exposure, HFE gene mutation, HIV or hep C. PCT is diagnosed by skin manifestations, distinct urinary porphyrin profile and identification of isocoproporphyrin in faeces. Phlebotomy is the preferred choice of treatment for patients with PCT and iron overload or HFE gene mutation.


Disclosures:


Ahmed Elhawary, MD¹, Kymberly Watt, MD¹, Ummah Salma Nisar, MD², Mounika Angirekula, MD³. P3883 - Identification of a Novel Mutation in Porphyria Cutanea Tarda, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.