Porphyrias

Abstract

Hereditary porphyrias are a group of eight metabolic disorders of the haem biosynthesis pathway that are characterised by acute neurovisceral symptoms, skin lesions, or both. Every porphyria is caused by abnormal function of a separate enzymatic step, resulting in a specific accumulation of haem precursors. Seven porphyrias are the result of a partial enzyme deficiency, and a gain of function mechanism has been characterised in a new porphyria. Acute porphyrias present with acute attacks, typically consisting of severe abdominal pain, nausea, constipation, confusion, and seizure, and can be life-threatening. Cutaneous porphyrias present with either acute painful photosensitivity or skin fragility and blisters. Rare recessive porphyrias usually manifest in early childhood with either severe cutaneous photosensitivity and chronic haemolysis or chronic neurological symptoms with or without photosensitivity. Porphyrias are still underdiagnosed, but when they are suspected, and dependent on clinical presentation, simple first-line tests can be used to establish the diagnosis in all symptomatic patients. Diagnosis is essential to enable specific treatments to be started as soon as possible. Screening of families to identify presymptomatic carriers is crucial to decrease risk of overt disease of acute porphyrias through counselling about avoidance of potential precipitants.

Liver Fibrosis Associated with Iron Accumulation Due to Long-Term Heme-Arginate Treatment in Acute Intermittent Porphyria: A Case Series

“…Direct DNA sequencing has become the gold standard for diagnostic confirmation and defining the underlying genetic defects. This also allows counseling of family members, thereby preventing attacks in those with latent disease (Puy et al 2010;Herrick and McColl 2005).…”

“…In case of an acute attack, treatment consists of intravenous administration of carbohydrates (minimum of 300 g/day), heme-arginate preparations (3 mg/kg heme arginate once daily for 4 days), and further supportive measures (e.g., pain treatment with safe drugs). The intravenously administrated heme inhibits the upregulation of ALA synthase in the liver resulting in a dramatic reduction of urinary and plasma ALA and PBG (Puy et al 2010). Liver transplantation has become a valid treatment option in selected patients with recurrent attacks and significant disabling symptoms with poor quality of life (Seth et al 2007;Singal et al 2014).…”

“…Patients suffer from acute neurovisceral attacks with abdominal pain, nausea, vomiting, and neuropsychiatric symptoms. These acute attacks, which can be life-threatening, are commonly treated with carbohydrate solutions and intravenous administration of heme-arginate preparations (Puy et al 2010). Hemearginate molecules contain the central iron molecule, the reactive center of the heme molecule.…”

“…Hemearginate molecules contain the central iron molecule, the reactive center of the heme molecule. Less than 10% of patients develop recurrent attacks (Puy et al 2010) and therefore require heme-arginate preparations on a regular basis for several years, which can result in progressive iron overload. We present three AIP cases developing a distinct iron overload secondary to the heme-arginate treatment, complicated with the development of liver fibrosis, confirmed on pathology.…”

Dual‐wavelength excitation for fluorescence‐based quantification of zinc protoporphyrin IX and protoporphyrin IX in whole blood

“…Decreased ferrochelatase enzymatic activity in erythropoietic protoporphyria also produces massive increases in erythrocyte PPIX, but without an increase in ZnPP [3,12]. Erythrocyte PPIX may also be elevated in aminolevulinic acid dehydratase deficiency porphyria while ZnPP accumulates in congenital erythropoietic porphyria and hepatoerythropoietic porphyria [13,14]. In the remaining forms of porphyria, erythrocyte non-heme protoporphyrins generally lie within the reference range [13].…”