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Diagnosing Porphyria

Diagnosis in infants and children

When Should Prepubertal Children be Tested?​

Biochemical testing

Biochemical tests (urine or stool porphyrin testing) are of little value until puberty as the characteristic biochemical features of AIP, VP, PCT and HCP, like the clinical features, only manifest thereafter, usually from the age of 16-20 onwards.

There are rare exceptions:

Children with characteristic vesiculo-erosive skin disease suggestive of porphyria

Children with typical blistering and erosions suggestive of VP, HCP and PCT may have the homozygous forms of these disorders, or may have the recessive disorder congenital erythropoietic protoporphyria (CEP). See Unusual forms of porphyria. In such a case, biochemical tests should be performed and will be strongly positive. All of these conditions are extraordinarily uncommon.

Children with immediate photosensitivity suggestive of erythropoietic protoporphyria (EPP)

EPP, unlike the other porphyrias, typically has its onset in childhood. The clinical presentation is quite different to the other porphyrias (Read Erythropoietic protoporphyria) and the diagnosis is frequently not considered for many years. Such children react strongly to sun exposure with erythema and pain in the exposed areas, and may develop skin oedema. Typically the symptoms arise after a period of exposure, such as 30 minutes, and may take 1-2 days to subside afterwards. The diagnosis is easily made by demonstrating fluorescence of red blood cells under ultraviolet light, and by performing a plasma fluorescence scan and erythrocyte protoporphyrin quantitation. The first clue may be an abnormally vigorous response to phototherapy for neonatal jaundice.

Children with unusual presentations which might represent acute attacks

Acute attacks are vanishingly rare in children with "normal" forms of porphyria (if they occur at all). Children with suggestive symptoms may however be tested to exclude rare homozygous forms of porphyria such as acute intermittent porphyria (AIP) and the recessive disorder ALA dehydratase porphyria. (Hereditary tyrosinaemia is another condition to consider.)

Rarity of these presentations

It is worth emphasising the rarity of these childhood disorders. In South Africa, we are aware of four cases of homozygous VP of which only two presented in childhood, two cases of CEP, one case of homozygous PCT and approximately 20 families with EPP—the only disorder which family doctors and paediatricians should really be looking for. We have not encountered the other disorders.

Dna (Genetic) Testing

DNA testing is accurate at any age provided the actual mutation carried in the child's family has been identified. In the case of South African families carrying the common R59W mutation (See Variegate porphyria), this is a standard test which is offered by several laboratories (Read Diagnosis of porphyria and the pages thereafter). In the case of any other mutation, or any other porphyria, one needs to make contact with the laboratory which identified the mutation and find out whether they are able to test for it in the child. Provided the mutation is known in the family and is appropriately tested for, such a result is 100% accurate in proving inheritance or otherwise of the condition.

Bear in mind however that the presence of a mutation such as the R59W mutation is of no value whatsoever in predicting the likely effect of the disease in later life. Our own research has shown that 60% of adults who inherit this mutation show no effect at all—not even skin disease. In AIP the rate of asymptomatic carriage is probably even higher. Hence there is no urgencyin making the diagnosis in a healthy child. The only possible advantage is that the child can be accustomed to taking drug precautions and to looking after the skin, not because this is actually necessary during the asymptomatic period in childhood, but purely in preparation for adulthood.

Thus, if blood is drawn from a child for any other medical indication, the parents may wish to have a sample sent for DNA testing. In general we do not recommend subjecting the child to a blood examination specifically to determine inheritance of porphyria.

Testing at and After Puberty

Since VP and AIP manifest after puberty, it is essential that children with a family history are carefully screened for these disorders at about the age of 14-16. If a DNA diagnosis has already been made, then this may not be necessary. If the DNA diagnosis is not known, it should be requested provided the mutation in the family has been identified and can be tested for.

In all other cases, urine and blood should be submitted for testing as set out in Diagnosing porphyria: patients with a family history. If tests are negative, they should be repeated every 2 years until the age of about 22, since biochemical expression may not develop immediately (the problem of "silent carriers").

Until a diagnosis of AIP or VP has been definitively excluded (which effectively means by DNA testing), all such children and young adults should observe strict drug precautions (See Drug prescription in patients with porphyria) and, should they develop abdominal pain, require immediate testing for a possible acute attack.

Testing for Porphyria at Birth

A specimen of cord blood taken from the umbilical cord at the time of delivery provides an easy source of DNA for a genetic diagnosis of porphyria without hurting the infant. If the case of an identified mutation, such as the common South African mutation for variegate porphyria (R59W), it is simple to determine whether the infant has inherited the mutation. Patients and their spouses should discuss this possibility with their obstetrician during the pregnancy. If they decide to request this, then a specimen of cord blood should be sent in an EDTA (mauve-topped full blood count) tube to the laboratory for testing. Note again that it is essential that the mutation has been accurately identified in the parent, as the result is otherwise meaningless.

Prenatal Testing

Except in the most special (and therefore rare) circumstances, such as when a couple has already produced a child with a homozygous form of porphyria, prenatal testing for the inheritance of porphyria is definitely not indicated. Porphyrias are in the absence of homozygosity relatively benign disorders, and termination of pregnancy on the grounds of porphyria should therefore never be an option. Hence prenatal diagnosis serves no purpose, making the risks to fetal well-being of an invasive diagnostic procedure unacceptable.