Acute Hepatic Porphyria

Abstract

The porphyrias comprise a set of diseases, each representing an individual defect in one of the eight enzymes mediating the pathway of heme synthesis. The diseases are genetically distinct but have in common the overproduction of heme precursors. In the case of the acute (neurologic) porphyrias, the cause of symptoms appears to be overproduction of a neurotoxic precursor. For the cutaneous porphyrias, it is photosensitizing porphyrins. Some types have both acute and cutaneous manifestations. The clinical presentation of acute porphyria consists of abdominal pain, nausea, and occasionally seizures. Only a small minority of those who carry a mutation for acute porphyria have pain attacks. The triggers for an acute attack encompass certain medications and severely decreased caloric intake. The propensity of females to acute attacks has been linked to internal changes in ovarian physiology. Symptoms are accompanied by large increases in delta-aminolevulinic acid and porphobilinogen in plasma and urine. Treatment of an acute attack centers initially on pain relief and elimination of inducing factors such as medications; glucose is administered to reverse the fasting state. The only specific treatment is administration of intravenous hemin. An important goal of treatment is preventing progression of the symptoms to a neurological crisis. Patients who progress despite hemin administration have undergone liver transplantation with complete resolution of symptoms. A current issue is the unavailability of a rapid test for urine porphobilinogen in the urgent-care setting.

Experiences and concerns of patients with recurrent attacks of acute hepatic porphyria: A qualitative study

“…A topic guide was developed based on a review of the literature regarding QoL, patient experiences, triggers that cause acute attacks 7,8–10,13–18 and expertise of the research team. The Guide consisted of five sections, each with a brief introduction followed by one to three open-ended questions (Table 2).…”

“…However, some patients with recurrent attacks receive prophylactic hemin infusions, ranging from weekly to monthly, to prevent hospitalization 10,13,14 .…”

A mouse model of hereditary coproporphyria identified in an ENU mutagenesis screen

“…This enzyme is responsible for the conversion of coproporphyrinogen III into protoporphyrinogen IX in the mitochondria of haem-synthesising cells. More than 65 mutations within the CPOX gene have been characterised in humans so far, encompassing missense, nonsense, frameshift and insertion/deletion mutations, each with variable penetrance, enzyme functionality and clinical manifestation ( Bissell and Wang, 2015 ). Clinically, porphyria usually emerges in adolescence with acute attacks triggered by factors that activate hepatic enzymes, such as fasting, alcohol, sulphonamide antibiotics, and hormones such as progesterone ( Bissell and Wang, 2015 ).…”

“…More than 65 mutations within the CPOX gene have been characterised in humans so far, encompassing missense, nonsense, frameshift and insertion/deletion mutations, each with variable penetrance, enzyme functionality and clinical manifestation ( Bissell and Wang, 2015 ). Clinically, porphyria usually emerges in adolescence with acute attacks triggered by factors that activate hepatic enzymes, such as fasting, alcohol, sulphonamide antibiotics, and hormones such as progesterone ( Bissell and Wang, 2015 ). Biochemically, HCP presents with a marked increase in porphyrin precursors, such as porphobilinogen (PBG), as well as porphyrins, notably coproporphyrinogen III, which accumulate and are detected in urine and faeces in high concentrations during episodic attacks, but can be normal or only marginally elevated during latent periods.…”

Severe hydroxymethylbilane synthase deficiency causes depression-like behavior and mitochondrial dysfunction in a mouse model of homozygous dominant acute intermittent porphyria

“…hormones) or exogenous (e.g. drugs) precipitating factors that induce the hepatic expression of δaminolevulinic acid synthase 1, the first and rate-limiting enzyme of heme biosynthesis [8][9][10][11] resulting in the massive accumulation of the putatively neurotoxic porphyrin precursors, δ-aminolevulinic acid (ALA) and porphobilinogen (PBG) in the liver plasma and urine.…”