Case Report Describes Man With Two Distinct Porphyria-causing Mutations

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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abdominal pain and porphyria


An Argentinian man with two different porphyria-causing mutations was described in a new case report.

The unusual findings highlight the importance of thorough clinical and molecular analyses in such cases to better define treatment strategies, researchers said.

The report, “Acute Intermittent Porphyria in a Man with Dual Enzyme Deficiencies,” was published in the journal Case Reports in Genetics.

Porphyrias are a group of genetic disorders characterized by high levels of porphyrins in the body. Porphyrins are compounds generated in the production of heme, an iron-containing pigment that is essential for the transport of oxygen in the bloodstream and for liver function.

The most common type of porphyria is porphyria cutanea tarda (PCT), which is characterized primarily by painful skin lesions. PCT is caused by mutations in the gene uroporphyrinogen decarboxylase (UROD), which provides instructions for making a protein of the same name that is required for the production of heme.

A team in Argentina described the case of a 68-year-old man who was diagnosed with PCT based on laboratory findings, as well as genetic testing that confirmed the presence of a mutation in UROD. His medical history included symptoms such as skin fragility, macules and dark urine for more than 30 years.

The patient had five children, the youngest of whom (a son) went to the hospital at age 40 with severe abdominal pain, vomiting and fever, but notably no skin symptoms.

These manifestations are indicative of another type of porphyria, acute intermittent porphyria (AIP), as supported by laboratory tests.

Genetic testing revealed that the son had inherited the same UROD mutation detected in the father. This mutation was not detected in any of the three siblings who agreed to undergo genetic testing.

In addition, the son had another mutation, which was not detected in any of his tested relatives: a mutation in the gene hydroxymethylbilane synthase (HMBS), the known cause of AIP. No prior case in Argentina had reported this mutation, the scientists said.

“Porphyrias are infrequent diseases, but it is even more rare to find mutations in different genes that may cause two types of porphyria in one individual,” the researchers wrote.

The patient’s AIP was treated with folic acid and vitamin B supplements, in addition to a specialized diet and carbohydrate loading for acute attacks of porphyria. Symptomatic treatments (such as clonazepam, an anti-epileptic drug) and psychological therapy also were provided. After six months, the patient was stable, without any new AIP attacks.

“It must be emphasized the importance of carrying out a complete clinical, biochemical, and molecular study to apply the specific treatment, which is critical in cases of coexistence of a cutaneous porphyria with an acute porphyria since the therapy and medical care in both cases are rather different,” the researchers concluded.