Porphyria cutanea tarda, familial type

Porphyria Cutanea Tarda, Familial Type

Porphyria cutanea tarda, familial type is a subtype of porphyria cutanea tarda (PCT), which is the most common form of porphyria. Porphyrias are a group of rare metabolic disorders caused by deficiencies in the enzymes involved in the heme biosynthesis pathway. The familial type of PCT is characterized by a genetic predisposition to the disease, often inherited in an autosomal dominant pattern.

Pathophysiology

Porphyria cutanea tarda results from a deficiency of the enzyme uroporphyrinogen decarboxylase (UROD), which leads to the accumulation of porphyrins in the liver and subsequently in the skin. In the familial type, there is a partial deficiency of UROD due to genetic mutations. This enzyme deficiency causes an overproduction and accumulation of porphyrins, particularly uroporphyrin and heptacarboxylate porphyrin, which are excreted in the urine.

Clinical Features

Patients with familial PCT typically present with cutaneous symptoms, including:

• Photosensitivity: Skin fragility and blistering on sun-exposed areas such as the hands, forearms, and face.
• Hyperpigmentation and hypertrichosis: Darkening of the skin and excessive hair growth, particularly on the face.
• Scarring and milia: Formation of small, white cysts on the skin.

Diagnosis

The diagnosis of familial PCT is based on clinical presentation, biochemical tests, and genetic testing. Key diagnostic tests include:

• Measurement of porphyrins in urine, plasma, and stool.
• Genetic testing for mutations in the UROD gene.
• Liver function tests and screening for associated conditions such as hemochromatosis, hepatitis C, and HIV.

Management

Management of familial PCT involves both lifestyle modifications and medical treatments:

• Avoidance of alcohol and estrogen, which can exacerbate symptoms.
• Phlebotomy: Regular removal of blood to reduce iron levels, which can help decrease porphyrin production.
• Low-dose hydroxychloroquine or chloroquine: These medications can help mobilize porphyrins from the liver.

Prognosis

With appropriate management, patients with familial PCT can lead normal lives. However, untreated PCT can lead to complications such as liver damage and increased risk of hepatocellular carcinoma.

Also see

• Porphyria
• Heme biosynthesis
• Uroporphyrinogen decarboxylase
• Photosensitivity