Klinisk Biokemi i Norden · 3 2013
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sequencing of the
UROD
gene was used as the reference
standard to establish different diagnostic strategies for
the differentiation of sporadic and familial PCT and
to examine their diagnostic accuracy (7). In our large
national sample consisting of more than 240 PCT
patients, a
UROD
mutation was identified in over 50%
of cases. Using this data as basis showed that UROD
activity has high diagnostic accuracy for differentiating
the two types of PCT. Clinical and laboratory data were
also collected for all patients and used to establish other
diagnostic models for the identification of familial PCT.
In clinical practise, however, these models will be popu-
lation-dependent and may have low predictive power.
Two frequently occurring mutations, c.636+1G>C and
c.578G>C, constituted more than 70% of the familial
cases in our Norwegian patient cohort. Gene marker
studies indicated that the latter is a founder mutation
originating in the north-western part of Southern Nor-
way, being the first founder mutation identified for PCT.
In most other populations, familial PCTmakes up only
20 - 25% of cases (8-12).
Foto: Henrik Alfthan.
Table 1.
Main clinical presentation and characteristics of the porphyrias.
Main clinical presentation
Affected enzyme
Gene(s) Inheritance
a
Acute symptoms
ALA dehydratase deficiency
b
Acute attacks/chronic neuropathy ALA dehydratase
ALAD
AR
Acute intermittent porphyria
(AIP)
Acute attacks
Porphobilinogen deaminase
HMBS
AD
Acute and cutaneous symptoms
Hereditary coproporphyria
(HCP)
Acute attacks and/or skin fragility
and blisters
Coproporphyrinogen oxidase
CPOX
AD
Variegate porphyria (VP)
Acute attacks and/or skin fragility
and blisters
Protoporphyrinogen oxidase
PPOX
AD
Cutaneous symptoms
Congenital erythropoietic
porphyria (CEP)
Severe photosensitivity
Haemolysis
Uroporphyrinogen III synthase
UROS/
GATA-1
AR
Porphyria cutanea tarda (PCT) Skin fragility and blisters
Uroporphyrinogen decarboxylase
UROD
c
AD/sporadic
Erythropoietic protoporphyria
(EPP)
- Ferrochelatase-deficient
- ALAS2-gain of function
mutation
Burning sensation in skin after
light exposure
(Acute fulminant liver failure)
Ferrochelatase
Erythroid ALA synthase
FECH
ALAS2
AR
X-linked D
a
AR; autosomal recessive, AD; autosomal dominant, D; dominant.
b
ALA; δ-aminolevulinic acid.
c
In addition, sporadic/non-hereditary and toxic variants.
