Penetrance

PPOX pathogenic variants that result in VP produce little or no functional enzyme; the approximately 50% of normal residual enzyme activity results primarily from the normal allele. Penetrance is low, but may be increased by factors that increase the demand for hepatic heme synthesis. Penetrance is likely influenced by modifying genes that remain to be identified.

Source: GeneReviews — "Variegate Porphyria"

Diagnostic Criteria

Suggestive Findings

Variegate porphyria (VP) should be suspected in individuals with the following clinical findings and initial laboratory findings.

Clinical findings

Source: GeneReviews — "Variegate Porphyria"

Differential Diagnosis

The genetic porphyrias comprise a group of distinct diseases, each resulting from alteration of a specific step in the heme synthesis pathway that results in characteristic patterns of accumulation of pathway intermediates. In the porphyrias are grouped by their principal clinical manifestations (neurovisceral or cutaneous) and the tissue origin of the excess production of pathway intermediates: liver (i.e., hepatic); or bone marrow (i.e., erythropoietic). Porphyrias with neurologic manifestations are considered acute because the symptoms usually occur as discrete, severe episodes, which may be induced by endogenous hormones, drugs and dietary changes; they are difficult to diagnose due to their rarity and the nonspecific nature of symptoms, even when severe.

Source: GeneReviews — "Variegate Porphyria"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and to plan the management of an individual diagnosed with variegate porphyria (VP), the following clinical and laboratory evaluations (if not performed as part of the evaluation that led to the diagnosis) are recommended:

• Degree of elevations on plasma and urine porphyrins and urine porphobilinogen (PBG), if not determined at the time of diagnosis

• Clinical evaluation of any current acute neurovisceral manifestations to determine the need for hospital admission and treatment with hemin.

• Nervous system. Assessment of the extent of neurologic involvement causing paresis, pain or sensory changes

• Psychiatric evaluation if depression or other psychiatric features are present

• Liver. Liver function tests to indicate chronic liver involvement and liver imaging in patients older than age 50 years

• Kidneys. Kidney function tests to assess for presence and progression of kidney damage

• Skin. Assessment of blistering cutaneous lesions to assess their relationship to VP

• Contributions of medications , diet, and concurrent conditions to severity of VP

• Consultation with a clinical geneticist and/or genetic counselor

Surveillance Guidelines

Hepatocellular carcinoma may develop especially after age 50 years in patients with acute porphyrias and persistent elevations in porphobilinogen or porphyrins; liver imaging at six-month intervals beginning at age 50 years may detect early lesions .

Source: GeneReviews — "Variegate Porphyria"