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Familial porphyria cutanea tarda(PCT)

MedGen UID:
75669
Concept ID:
C0268323
Disease or Syndrome
Synonyms: PCT; PCT, ''FAMILIAL'' TYPE; PCT, TYPE II; PORPHYRIA CUTANEA TARDA, TYPE II; PORPHYRIA, HEPATOCUTANEOUS TYPE; UROD DEFICIENCY; UROPORPHYRINOGEN DECARBOXYLASE DEFICIENCY
SNOMED CT: PCT (porphyria cutanea tarda) type II (59229005); Familial porphyria cutanea tarda (59229005); Hereditary porphyria cutanea tarda (59229005)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): UROD (1p34.1)
 
Monarch Initiative: MONDO:0008296
OMIM®: 176100
Orphanet: ORPHA443062

Definition

Familial porphyria cutanea tarda (F-PCT) is characterized by: skin findings including blistering over the dorsal aspects of the hands and other sun-exposed areas of skin, skin friability after minor trauma, facial hypertrichosis and hyperpigmentation, and severe thickening of affected skin areas (pseudoscleroderma); and an increased risk for hepatocellular carcinoma (HCC). [from GeneReviews]

Additional descriptions

From OMIM
Porphyria cutanea tarda (PCT) is characterized by light-sensitive dermatitis and the excretion of large amounts of uroporphyrin in urine (Elder et al., 1980). De Verneuil et al. (1978) and others classified porphyria cutanea tarda, the most common type of porphyria, into 2 types: type I (176090), or 'sporadic' type, associated with approximately 50% level of uroporphyrinogen decarboxylase (UROD) in liver (Elder et al., 1978; Felsher et al., 1982), and type II, or 'familial' type, characterized by 50% deficient activity of the same enzyme in many tissues (Kushner et al., 1976; Elder et al., 1980). PCT type II is an autosomal dominant disorder with low penetrance and constitutes about 20% of cases of PCT. Recognized exacerbating factors of PCT include iron overload, excessive use of alcohol, exposure to polyhalogenated aromatic chemicals, exposure to estrogens, chronic viral hepatitis C, HIV infections, and mutation in the HFE gene (613609) that are responsible for hereditary hemochromatosis (235200) (review by Lambrecht et al., 2007).  http://www.omim.org/entry/176100
From MedlinePlus Genetics
The porphyrias can also be split into erythropoietic and hepatic types, depending on where damaging compounds called porphyrins and porphyrin precursors first build up in the body. In erythropoietic porphyrias, these compounds originate in the bone marrow. Erythropoietic porphyrias include erythropoietic protoporphyria and congenital erythropoietic porphyria. Health problems associated with erythropoietic porphyrias include a low number of red blood cells (anemia) and enlargement of the spleen (splenomegaly). The other types of porphyrias are considered hepatic porphyrias. In these disorders, porphyrins and porphyrin precursors originate primarily in the liver, leading to abnormal liver function and an increased risk of developing liver cancer.

Environmental factors can strongly influence the occurrence and severity of signs and symptoms of porphyria. Alcohol, smoking, certain drugs, hormones, other illnesses, stress, and dieting or periods without food (fasting) can all trigger the signs and symptoms of some forms of the disorder. Additionally, exposure to sunlight worsens the skin damage in people with cutaneous porphyrias.

Other types of porphyria, called acute porphyrias, primarily affect the nervous system. These disorders are described as "acute" because their signs and symptoms appear quickly and usually last a short time. Episodes of acute porphyria can cause abdominal pain, vomiting, constipation, and diarrhea. During an episode, a person may also experience muscle weakness, seizures, fever, and mental changes such as anxiety and hallucinations. These signs and symptoms can be life-threatening, especially if the muscles that control breathing become paralyzed. Acute porphyrias include acute intermittent porphyria and ALAD deficiency porphyria. Two other forms of porphyria, hereditary coproporphyria and variegate porphyria, can have both acute and cutaneous symptoms.

Researchers have identified several types of porphyria, which are distinguished by their genetic cause and their signs and symptoms. Some types of porphyria, called cutaneous porphyrias, primarily affect the skin. Areas of skin exposed to the sun become fragile and blistered, which can lead to infection, scarring, changes in skin coloring (pigmentation), and increased hair growth. Cutaneous porphyrias include congenital erythropoietic porphyria, erythropoietic protoporphyria, hepatoerythropoietic porphyria, and porphyria cutanea tarda.

Porphyria is a group of disorders caused by abnormalities in the chemical steps that lead to heme production. Heme is a vital molecule for all of the body's organs, although it is most abundant in the blood, bone marrow, and liver. Heme is a component of several iron-containing proteins called hemoproteins, including hemoglobin (the protein that carries oxygen in the blood).  https://medlineplus.gov/genetics/condition/porphyria

Clinical features

From HPO
Porphyrinuria
MedGen UID:
57493
Concept ID:
C0151861
Disease or Syndrome
Abnormally increased excretion of porphyrins in the urine.
Cirrhosis of liver
MedGen UID:
7368
Concept ID:
C0023890
Disease or Syndrome
A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function.
Hepatocellular carcinoma
MedGen UID:
389187
Concept ID:
C2239176
Neoplastic Process
Hepatocellular carcinoma is the major histologic type of malignant primary liver neoplasm. It is the fifth most common cancer and the third most common cause of death from cancer worldwide. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. Hepatoblastomas comprise 1 to 2% of all malignant neoplasms of childhood, most often occurring in children under 3 years of age. Hepatoblastomas are thought to be derived from undifferentiated hepatocytes (Taniguchi et al., 2002).
Reduced uroporphyrinogen decarboxylase activity
MedGen UID:
1842076
Concept ID:
C5826607
Finding
Activity of the enzyme uroporphyrinogen decarboxylase (UROD; EC 4.1.1.37) below the lower limit of normal.
Alopecia
MedGen UID:
7982
Concept ID:
C0002170
Finding
A noncongenital process of hair loss, which may progress to partial or complete baldness.
Scleroderma
MedGen UID:
3770
Concept ID:
C0011644
Disease or Syndrome
A chronic autoimmune phenomenon characterized by fibrosis (or hardening) and vascular alterations of the skin.
Onycholysis
MedGen UID:
39324
Concept ID:
C0085661
Disease or Syndrome
Detachment of the nail from the nail bed.
Fragile skin
MedGen UID:
66826
Concept ID:
C0241181
Finding
Skin that splits easily with minimal injury.
Cutaneous photosensitivity
MedGen UID:
87601
Concept ID:
C0349506
Pathologic Function
An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin.
Facial hypertrichosis
MedGen UID:
342000
Concept ID:
C1851400
Finding
Excessive, increased hair growth located in the facial region.
Hyperpigmentation in sun-exposed areas
MedGen UID:
812207
Concept ID:
C3805877
Finding

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFamilial porphyria cutanea tarda

Professional guidelines

PubMed

Cabezas Arteaga JE, Vieira FMJ, Silva Dos Reis VM
Int J Dermatol 2019 Aug;58(8):925-932. Epub 2019 Feb 17 doi: 10.1111/ijd.14398. PMID: 30773624
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Sarkany RP
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Recent clinical studies

Etiology

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Br J Dermatol 2007 Sep;157(3):501-7. Epub 2007 Jul 11 doi: 10.1111/j.1365-2133.2007.08064.x. PMID: 17627795
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Diagnosis

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Hum Mutat 2000 Sep;16(3):269-70. doi: 10.1002/1098-1004(200009)16:3<269::AID-HUMU12>3.0.CO;2-#. PMID: 10980536
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Therapy

Rasheed E, Savage S, Walsh E, Brazil N, Ralph N, Gorman PO, Crowley V
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Battle AM, Stella AM, De Kaminsky AR, Kaminsky C, Mariano HG
Br J Dermatol 1987 Mar;116(3):407-15. doi: 10.1111/j.1365-2133.1987.tb05856.x. PMID: 3567077

Prognosis

Phillips JD, Parker TL, Schubert HL, Whitby FG, Hill CP, Kushner JP
Blood 2001 Dec 1;98(12):3179-85. doi: 10.1182/blood.v98.12.3179. PMID: 11719352
McManus JF, Begley CG, Sassa S, Ratnaike S
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Castaño Suárez E, Zamarro Sanz O, Guerra Tapia A, Enríquez de Salamanca R
Dermatology 1996;193(4):332-5. doi: 10.1159/000246284. PMID: 8993961
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Clinical prediction guides

Dereure O, Jumez N, Bessis D, Gallix B, Guillot B
Acta Derm Venereol 2008;88(4):341-5. doi: 10.2340/00015555-0472. PMID: 18709302
Méndez M, Poblete-Gutiérrez P, García-Bravo M, Wiederholt T, Morán-Jiménez MJ, Merk HF, Garrido-Astray MC, Frank J, Fontanellas A, Enríquez de Salamanca R
Br J Dermatol 2007 Sep;157(3):501-7. Epub 2007 Jul 11 doi: 10.1111/j.1365-2133.2007.08064.x. PMID: 17627795
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Battle AM, Stella AM, De Kaminsky AR, Kaminsky C, Mariano HG
Br J Dermatol 1987 Mar;116(3):407-15. doi: 10.1111/j.1365-2133.1987.tb05856.x. PMID: 3567077

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