Clinical Guidance

Because of the limited number of families known to have XLP, no genotype-phenotype correlations have been identified.

Source: GeneReviews — "X-Linked Protoporphyria"

Penetrance

XLP appears to be 100% penetrant in males. In heterozygous females, clinical variability is attributed to random X-chromosome inactivation. Symptomatic females have been reported .

Source: GeneReviews — "X-Linked Protoporphyria"

Diagnostic Criteria

There are no established guidelines or diagnostic algorithms.

Suggestive Findings

X-linked protoporphyria (XLP) should be suspected in individuals with the following clinical findings and initial laboratory findings.

Clinical findings

• Cutaneous photosensitivity, usually beginning in childhood

• Burning, tingling, pain, and itching of the skin (the most common findings); may occur within minutes of sun/light exposure, followed later by erythema and swelling

• Painful symptoms; may occur without obvious skin damage

• Absent or sparse blisters and bullae

Note: The absence of skin damage (e.g., scarring), vesicles, and bullae often make it difficult to suspect the diagnosis.

• Hepatic complications, particularly cholestatic liver disease, may develop in fewer than 5% of affected individuals.

Source: GeneReviews — "X-Linked Protoporphyria"

Differential Diagnosis

Other causes of the X-linked protoporphyria (XLP) phenotype include the following:

• Polymorphous light eruption

• Solar urticaria

• Drug-induced photosensitivity

Source: GeneReviews — "X-Linked Protoporphyria"

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs of an individual diagnosed with X-linked protoporphyria (XLP), the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended :

• Comprehensive medical history including history of phototoxicity

• Complete physical examination, including thorough skin examination

• Assessment of erythrocyte protoporphyrin levels (free and zinc-chelated), complete blood count with indices to evaluate for anemia, and iron profile (including ferritin) to monitor iron stores

• Assessment for liver disease:

• Hepatic function panel (including serum aminotransferases)

• Imaging studies such as abdominal ultrasound examination if cholelithiasis is suspected

• Newer imaging modalities such as Fibroscan® may be useful in evaluating liver fibrosis; however, this has not been validated in erythropoietic protoporphyria, autosomal recessive (EPP-AR) or XLP.

• A liver biopsy may be indicated to evaluate for protoporphyric liver disease.

• Vitamin D studies to evaluate for deficiency as affected individuals are predisposed to vitamin D insufficiency resulting from sun avoidance

• Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Acute photosensitivity. Although several treatments have been proposed, most have been tried only in a single individual or a small number of patients.

Source: GeneReviews — "X-Linked Protoporphyria"

Clinical Guidance

The following are appropriate:

• Avoidance of sunlight and UV light

• In patients with hepatic dysfunction, avoidance of alcohol and drugs that may induce cholestasis (e.g., estrogens)

• In patients with cholestatic liver failure, use of protective filters for artificial lights in the operating room to prevent phototoxic damage during procedures such as endoscopy and surgery

Source: GeneReviews — "X-Linked Protoporphyria"

Therapies Under Investigation

A Phase II clinical trial with MT-7117, an oral small molecule that works as a melanocortin 1 receptor agonist and increases skin pigmentation, has been completed. A Phase III clinical trial for adults and children is planned for MT-7117. Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "X-Linked Protoporphyria"

Surveillance Guidelines

Table 4.

Recommended Surveillance for Individuals with X-Linked Protoporphyria

System/Concern | Evaluation | Frequency

Erythrocyte

protoporphyrin levels

plasma total porphyrins | Both free zinc-chelated | Annually

Anemia

| Complete blood count w/indices

Iron store depletion

| Serum ferritin levels

Hepatic involvement

| Hepatic function (liver transaminases)

US exam (if cholelithiasis is suspected) | As indicated

Fibroscan® to evaluate for hepatic fibrosis

Vitamin D deficiency

| Vitamin D 25-OH levels whether or not receiving supplements | Annually

US = ultrasound

Source: GeneReviews — "X-Linked Protoporphyria"