Clinical Guide and Update on Porphyrias

Abstract

Physicians should be aware of porphyrias, which could be responsible for unexplained gastrointestinal, neurologic, or skin disorders. Despite their relative rarity and complexity, most porphyrias can be easily defined and diagnosed. They are caused by well-characterized enzyme defects in the complex heme biosynthetic pathway and are divided into categories of acute vs non-acute or hepatic vs erythropoietic porphyrias. Acute hepatic porphyrias (acute intermittent porphyria, variegate porphyria, hereditary coproporphyria, and aminolevulinic acid dehydratase deficient porphyria) manifest in attacks and are characterized by overproduction of porphyrin precursors, producing often serious abdominal, psychiatric, neurologic, or cardiovascular symptoms. Patients with variegate porphyria and hereditary coproporphyria can present with skin photosensitivity. Diagnosis relies on measurement of increased urinary 5-aminolevulinic acid (in patients with aminolevulinic acid dehydratase deficient porphyria) or increased 5-aminolevulinic acid and porphobilinogen (in patients with other acute porphyrias). Management of attacks requires intensive care, strict avoidance of porphyrinogenic drugs and other precipitating factors, caloric support, and often heme therapy. The non-acute porphyrias are porphyria cutanea tarda, erythropoietic protoporphyria, X-linked protoporphyria, and the rare congenital erythropoietic porphyria. They lead to the accumulation of porphyrins that cause skin photosensitivity and occasionally severe liver damage. Secondary elevated urinary or blood porphyrins can occur in patients without porphyria, for example, in liver diseases, or iron deficiency. Increases in porphyrin precursors and porphyrins are also found in patients with lead intoxication. Patients with porphyria cutanea tarda benefit from iron depletion, hydroxychloroquine therapy, and, if applicable, elimination of the hepatitis C virus. An a-melanocytestimulating hormone analogue can reduce sunlight sensitivity in patients with erythropoietic protoporphyria or Xlinked protoporphyria. Strategies to address dysregulated or dysfunctional steps within the heme biosynthetic pathway are in development.

Recent advances in the epidemiology and genetics of acute intermittent porphyria

“…Although a study in Finland found similar genotypes, penetrance differed greatly among families (32). This shows that the phenotype of AIP is not determined by the HMBS genotype alone but that other factors such as modifying genes and the environment also play a vital role in the pathogenesis of AIP attacks (6,24,25,32,70,71 (72). The correlation between genotype and phenotype is still a topic of interest in research on AIP.…”

Therapeutic strategies for acute intermittent porphyria

“…Treatment with ursodeoxycholic acid and cholestyramine is a potential option for patients with liver impairment. Elimination of redundant protoporphyrin via plasma exchange can also delay the progression of liver impairment (119). OLT is the most thorough treatment for liver failure and HCC.…”

A novel heterozygous mutation in the HMBS gene in a patient with acute intermittent porphyria and posterior reversible encephalopathy syndrome

“…Porphyrias is a group of rare, mostly inherited disorders that are each caused by a defect in a specific heme biosynthetic enzyme (1). acute intermittent porphyria [aiP; online Mendelian inheritance in Man (oMiM) id, 176000] is caused by the partial deficiency of hydroxymethylbilane synthase (HMBS; ec:4.3.1.8), an enzyme in the heme biosynthetic pathway (2).…”

“…With the advent of dna technology, genetic analysis has become the gold standard for the diagnosis of aiP (2). in total, >390 different mutations responsible for aiP have been reported so far (1), most of them in europe, particularly in northern europe (5).…”