Clinical, Biochemical and Molecular Characteristics of the Main Types of Porphyria

Abstract

Porphyrias are diverse disorders that arise from various inherited enzyme defects in the heme biosynthesis pathway, except for porphyria cutanea tarda (PCT), in which the enzyme deficiency in most cases is acquired. The biosynthetic blocks resulting from the defective enzymes are largely expressed either in the liver or bone marrow, the sites where the majority of heme is produced. Although the pathophysiologic mechanisms of the clinical manifestations of the porphyrias are not fully understood, two cardinal features prevail: skin photosensitivity and neurologic symptoms of intermittent autonomic neuropathy, acute neurovisceral attacks, and disorders of the nervous system. The primary diagnosis of the proband is based on biochemical testing, which is not always able to identify acute porphyrias, especially in asymptomatic family carriers when heme precursors and porphyrins excretion is normal, low-normal and high-reduced values of enzyme activity overlap, and hematological diseases responsible for abnormal blood cells distribution coexist. Molecular analysis of gene mutations responsible for each type of porphyria is the best diagnostic approach for symptomatic as well as presymptomatic gene carriers (Adv Clin Exp Med 2016, 25, 2, 361-368).

Pathophysiology, Pharmacology and Treatment of Acute Intermittent Porphyria: A Patient Case Description and Recommendations from the Current Literature

“…4 Regulatory mechanisms differ based on the site of production: erythroid heme synthesis depends mainly on the availability of iron, while hepatic heme synthesis is regulated by the free heme pool. 5 Heme synthesis begins with the formation of ALA within the mitochondria, catalyzed by 5-aminolevulinic acid synthase (ALAS).…”

An Extremely Rare Case of Congenital Erythropoietic Porphyria Diagnosed In Adulthood with Unusual Life Threatening Complications

“…Blistering, fragility and scarring of exposed oculocutaneous sites lead to mutilating deformities. [4] Chronic hemolytic anemia induces hypersplenism and bone marrow hyperplasia.…”

“…[4] Long-term cutaneous sequelae include scarred mutilated face, mitten hands, hypertrichosis and non-melanoma skin cancers. [3] Case reports describing such manifestations are there in literature.…”

“…[4] More than 49 mutations has described and the most common mutation is substitution of amino acid C73R that is associated with severe phenotype. [6] We couldn't perform genetic studies and more detailed biochemical evaluation due to unavailability of these expensive investigations at our setup.…”

“…Further EPP has autosomal dominant inheritance (95% of cases) and there is marked elevation of protoporphyrins in erythrocytes. [4] Splenectomy, hypertransfusion, and orally administered drugs such as charcoal and cholestyramine, which binds porphyrins have also been used to treat CEP. Blood transfusion reduces endogenous porphyrin synthesis by negative feedback and also raises hemocrit levels thus play a dual role.…”