Non-acute porphyrias

Gene: UROD

Green List (high evidence)

Relevant metabolic investigation: plasma fluorescence emission spectroscopy, fractionation of urinary and faecal porphyrins, erythrocyte total protoporphyrin fractionation (erythrocyte zinc protoporphyrin) (the latter indicated to aid in the differentiation of porphyria cutanea tarda (PCT) and hepatoerythropoietic porphyria (HEP))

PMID: 38940544 Aarsand describes that only ~20% of PCT patients have a pathogenic variant in the UROD gene, which is termed familial PCT. The remainder have sporadic PCT, which is not associated with UROD gene variants.

PMID: 39644053 Leaf reports that manifestations of PCT include blistering of sun-exposed skin and liver disease due to the accumulation of porphyrins. PCT occurs due to inhibition of the fifth enzyme of haem biosynthesis, uroporphyrinogen decarboxylase (UROD).

PMID: 30683557 Singal reports that PCT is the most common human porphyria and can occur at any age although most commonly in the 5th or 6th decade.

PMID:12735639 Bygum reports that the manifestation of active disease depends on extrinsic factors including alcohol, oestrogens, polyhalogenated aromatic hydrocarbons (PAH), hepatotrophic viruses and iron. About 40% of British or Danish patient populations with PCT carry the haemochromatosis related HFE pathogenic variant, c.845G>A, p.(Cys282Tyr), in either heterozygous or homozygous form. HIV infections are also implicated in the precipitation of PCT.

PMID: 24780981 Mykletun reports the prevalence of symptomatic PCT in Norway as 1 in 10,000 and PMID: 33085356 Shah of 1 in 25,000 in the United States.

PMID: 19233912 Aarsand reports that gene-marker studies of the c.578G>C pathogenic variant indicate that this is a founder mutation in Norway.

PMID: 26789143 Farrag reports that a genetic homogeneity has been observed in Spain with the predominance of the c.842 G>A, p.(Gly281Glu) pathogenic variant. By contrast, a great heterogeneity of pathogenic UROD variants has been found in Europe, Africa and America

PMID: 12735639 Bygum reports that familial PCT is characterized by an incomplete penetrance, as 90% of the gene mutation carriers remain asymptomatic throughout their lives

PMID: 38940544 Aarsand describes that genomic testing can be undertaken in families where a pathogenic variant in the UROD gene has been identified in an index patient, and it may be useful for those at risk of blistering skin lesions to avoid known susceptibility factors. However, familial PCT has a low penetrance so that the likelihood of developing clinical manifestations is small. If symptoms do occur, they can be treated, so that predictive genetic testing for PCT is optional.

PMID: 6112327 Elder reports that hepatoerythropoietic porphyria (HEP) is the rare, homozygous form of familial PCT.

The symptoms of HEP can range from mild which may present later in life (PMID: 30514647 Weiss) and are similar to familial PCT (PMID: 38940544 Aarsand) to severe where patients may present during infancy with extreme photosensitivity, skin lesions with fluid-filled blisters that break and heal slowly, hypertrichosis, and scarring over the affected skin areas (PMID: 24175354 Rudnick).

PMID: 38940544 Aarsand describes that mild or moderate HEP may be difficult to distinguish from PCT as both have similar urinary, faecal and plasma porphyrin patterns although erythrocyte zinc- chelated protoporphyrin is typically increased in HEP. Confirmation of the diagnosis will usually require the demonstration of two pathogenic UROD variants.

PMID:40534320 Dotto reported a homozygous variant c.185C>T, p.(Pro62Leu) that had previously been reported in a family, with severe, mutilating photosensitivity and marked biochemical abnormalities, in a patient with a milder phenotype, later onset, no systemic involvement and less skin damage.

Careful consideration should be given to the reporting of a single pathogenic variant as an incidental finding in the UROD gene, due to its low clinical penetrance.

Created: 4 Apr 2026, 6:33 p.m. | Last Modified: 4 Apr 2026, 6:33 p.m.

Panel Version: 1.35

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Porphyria cutanea tarda OMIM:176100; Hepatoerythropoietic porphyria OMIM:176100

Publications

• PMID: 38940544, 39644053, 30683557, 12735639, 24780981, 19233912, 26789143, 6112327, 30514647, 24175354, 40534320

Green List (high evidence)

Comment when marking as ready: As discussed in the GMS Gastrohepatology Specialist Test Group webex call 14th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.

Created: 24 Jan 2019, 4:21 p.m.

Initial gene list and info collated by Miranda Durkie Sheffield Diagnostic Genetics Service December 2018 on behalf of the GMS Gastrohepatology specialist test group. Gene Symbol submitted: UROD; Suggested intial gene rating: Green; Evidence for inclusion: none given; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given

Created: 7 Jan 2019, 3:53 p.m.

Green List (high evidence)

Clear evidence of association with the phenotype, unlikely to present via metabolic but not impossible so considered green

Created: 23 Feb 2017, 5:17 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Porphyria cutanea tarda (Porphyrias with erosive photodermatosis)

Publications

• 27604308
• 9792863