OPEN Research Support
head

PhD-student
Anne Lindegaard Christiansen
Department of Clinical Biochemistry and Pharmacology, Odense University Hospital


Projekt styring
Projekt status    Sampling ongoing
 
Data indsamlingsdatoer
Start 01.01.2016  
Slut 31.12.2018  
 



Porphyria cutanea tarda: Relations to iron overload, metabolic and cardiovascular diseases

Short summary

Porphyria cutanea tarda (PCT) is a rare hepatocutaneous disease caused by reduced activity of the fifth enzyme, uroporphyrinogen decarboxylase (UROD), in the haem biosynthesis.

In a cross sectional study we will investigate the metabolic and cardiovascular status of PCT patients and in an uncontrolled intervention study we will examine the metabolic and cardiovascular status before and after five months of standard treatment with phlebotomy. 


Rationale

Porphyria cutanea tarda (PCT) is a rare hepatocutaneous disease caused by reduced activity of the fifth enzyme, uroporphyrinogen decarboxylase (UROD), in the haem biosynthesis. The reduced enzyme activity leads to the accumulation of intermediates, porphyrins, which are deposited in the skin and liver. These porphyrins are reactive to light, and when people with PCT are exposed to light, they get blisters and sores and later on they may get hyperpigmentation and hypertrichosis.

Previous studies have shown that PCT patients are often iron-overloaded, have liver affection and increased risk of getting diabetes. From other studies, on patients not having PCT, it has been shown that the risk of developing cardiovascular disease is higher when iron-overloaded. In a cross sectional study we will investigate, whether PCT patients have increased risk for having vascular-metabolic disease.

One of the standard treatments is phlebotomy. Studies on non-PCT patients have shown that phlebotomy improves glucose metabolism and blood pressure; therefore we will examine PCT patients before and after their standard treatment.

The specific cause of the reduced enzyme activity is not clear, we do know however that PCT patients often have some sort of liver affection and that some people can develop PCT when taking estrogen, alcohol and medicine metabolized in the liver. With next generation sequencing we will analyze for mutations in 340 genes involved in the metabolism of substances in the liver to see if patients' reason for development of PCT can be found at gene level.


Description of the cohort

The study will investigate all PCT patients treated at the department of dermatology at Odense University hospital.

For the cross sectional study an age- and gender matched control group will be recruited.


Data and biological material

Porphyrins will be measured in urine, plasma and faeces.

Liver parameters, lipid profile, glucose parameters will be measured.

Functional tests: Pulse wave velocity, blood pressure, ankle brachial index and oral glucose tolerance test.

A biobank will be created.


Collaborating researchers and departments

Department of Clinical Biochemistry and Pharmacology, Odense University Hospital

  • Professor Lars Melholt Rasmussen

Department of Dermatology and Allergy Centre, Odense University Hospital

  • Professor Anette Bygum

Department of Clinical Genetics, Odense University Hospital

  • Professor Jens Michael Hertz
  • Associate professor Klaus Brusgaard

Publications associated with the project

Cutaneous Porphyrias: Causes, Symptoms, Treatments and the Danish Incidence 1989-2013. / Christiansen AL, Aagaard L, Krag A, Rasmussen LM, Bygum A. Acta Derm Venereol. 2016 Nov 2;96(7):868-872.