Clinically Important Features of Porphyrin and Heme Metabolism and the Porphyrias

Abstract

Heme, like chlorophyll, is a primordial molecule and is one of the fundamental pigments of life. Disorders of normal heme synthesis may cause human diseases, including certain anemias (X-linked sideroblastic anemias) and porphyrias. Porphyrias are classified as hepatic and erythropoietic porphyrias based on the organ system in which heme precursors (5-aminolevulinic acid (ALA), porphobilinogen and porphyrins) are chiefly overproduced. The hepatic porphyrias are further subdivided into acute porphyrias and chronic hepatic porphyrias. The acute porphyrias include acute intermittent, hereditary copro-, variegate and ALA dehydratase deficiency porphyria. Chronic hepatic porphyrias include porphyria cutanea tarda and hepatoerythropoietic porphyria. The erythropoietic porphyrias include congenital erythropoietic porphyria (Gűnther’s disease) and erythropoietic protoporphyria. In this review, we summarize the key features of normal heme synthesis and its differing regulation in liver versus bone marrow. In both organs, principal regulation is exerted at the level of the first and rate-controlling enzyme, but by different molecules (heme in the liver and iron in the bone marrow). We also describe salient clinical, laboratory and genetic features of the eight types of porphyria.

Porphyrias: A 2015 update

“…Treatment can be instituted immediately, while the precise type of porphyria is determined by analyzing the porphyrin excretion patterns in the urine, feces and plasma ( Table 1). The identification of the type of acute porphyria is necessary for the appropriate advice to be given to the patient and the family [7]. Plasma fluorescence emission spectroscopy is useful as a front-line test in all acute porphyrias because a peak at 624-627 nm establishes the diagnosis of VP.…”

“…In these cells, the rate of ALAS2 synthesis is increased only during the period of active heme synthesis and is regulated by iron availability. Ferrochelatase, the final enzyme of heme biosynthesis, and iron, its substrate, also play a significant role in controlling the rate of heme formation in erythroid cells [7].…”

Secret Underlying Unexplained Abdominal Pain, Neurological Symptoms and Intermittent Hypertension: Acute Intermittent Porphyria

“…Fluid restriction should be considered in case of SIADH in patients with AIP. The most important part of treatment is to avoid any stimulus that can trigger an attack [14]. Porphyria needs to be considered in the differential diagnosis of patients with neurological symptoms, unexplained abdominal pain and intermittent hypertension.…”

Porphyria: Analysis of Register from Brazilian Association of Porphyria (ABRAPO)

“…According to Bonkovsky HL et al, 3 characteristics of porphyria and its epidemiology is not yet well defined, but is observed to a greater prevalence in psychiatric patients (210:100000). 4,5 The pathogenesis caused by mutations in genes encoding enzymes involved in heme biosynthesis is classified and divided into acute ( AIP is autosomal dominant and the most common form of hepatic porphyria. The estimated prevalence is approximately 5:100000 in United States (US) and 1:75000 in Europe.…”