Penetrance

The penetrance of F-PCT is low, given that in addition to heterozygosity for a UROD pathogenic variant, other susceptibility factors need to be present (see Pathophysiology, ).

Source: GeneReviews — "Familial Porphyria Cutanea Tarda"

Diagnostic Criteria

Suggestive Findings

Familial porphyria cutanea tarda (F-PCT) should be suspected in a proband with the following clinical findings and suggestive biochemical findings. In some, there may also be a family history of PCT, although this is far from universal. Clinical features (typically developing in the 5th-6th decade):

Source: GeneReviews — "Familial Porphyria Cutanea Tarda"

Differential Diagnosis

Porphyria cutanea tarda (PCT) is the most common type of porphyria and encompasses both familial UROD-related porphyria cutanea tarda (~20% of all PCT) and type I sporadic PCT . Sporadic PCT (i.e., PCT that is not associated with a UROD pathogenic variant) is clinically indistinguishable from F-PCT and, like F-PCT, is highly influenced by susceptibility factors associated with PCT . Other types of hereditary porphyria in the differential diagnosis of F-PCT are summarized in . Table 4. Other Types of Porphyria in the Differential Diagnosis of Familial Porphyria Cutanea Tarda

Management Guidelines

No clinical practice guidelines for familial porphyria cutanea tarda (F-PCT) have been published.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with familial porphyria cutanea tarda (F-PCT), the following evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended:

Source: GeneReviews — "Familial Porphyria Cutanea Tarda"

Surveillance Guidelines

Monitor urinary porphyrin levels annually. For those who have been treated by phlebotomy, resume iron reduction by therapeutic phlebotomies if and when urinary uroporphyrins and heptacarboxylporphyrins increase to greater than 400 g/g creatinine to prevent recurrence of cutaneous signs. Note: Increase in urinary total porphyrins may also be caused by an increase in coproporphyrin (which is not relevant to F-PCT); thus, when urinary porphyrin levels are only moderately increased, urinary porphyrin fractionation should be performed. Because of reports of an association between diabetes mellitus and PCT , annual screening with a fasting glucose level is recommended, particularly in those with hypertension (blood pressure 135/80 mm Hg). Hepatocellular cancer (HCC) surveillance relies on a combination of serum alpha-fetoprotein determinations and hepatic ultrasonography or cross-sectional imaging (CT or MRI). No guidelines as to the frequency of these tests are currently available because of the rarity of F-PCT and even rarer occurrence of HCC. Surveillance is usually performed annually; however, in those with cirrhosis, hepatologists generally agree that surveillance for HCC should be at least every six months.

Source: GeneReviews — "Familial Porphyria Cutanea Tarda"