Neurovisceral Porphyrias: What a Hematologist Needs to Know

Abstract

The acute or inducible hepatic porphyrias comprise four inherited disorders of heme biosynthesis. They usually remain asymptomatic for most of the lifespan of individuals who inherit the specific enzyme deficiencies but may cause life-threatening attacks of neurovisceral symptoms. Failure to consider the diagnosis frequently delays effective treatment, and inappropriate diagnostic tests and/or mistaken interpretation of results may lead to misdiagnosis and inappropriate treatment. The four disorders are ALA dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria. Other conditions that clinically and biochemically may mimic acute porphyria include lead poisoning and hereditary tyrosinemia type I. The diagnosis of one of these acute porphyric syndromes should be considered in many patients with otherwise unexplained abdominal pain, severe constipation, systemic arterial hypertension, or other characteristic symptoms. Critical to the rapid diagnosis of the three most common of these disorders is demonstration of markedly increased urinary porphobilinogen (PBG) in a single-void urine specimen. The treatment of choice for all but mild attacks of the acute porphyrias is intravenous hemin therapy, which should be started as soon as possible. Intravenous glucose alone is recommended only for mild attacks (no weakness or hyponatremia) or until hemin is available.

Heme acts through the Bach1b/Nrf2a-MafK pathway to regulate exocrine peptidase precursor genes in porphyric zebrafish

“…Taken together, these data provide a molecular explanation of the frequently reported acute episodic abdominal pains with co-occurrences of nausea and vomiting in some porphyria individuals (Bickers, 1981; Pierach, 1982; Bonkovsky, 2005; Puy et al, 2010; Balwani and Desnick, 2012). In fact, treatment with hemin can effectively cure these symptoms, although the underlying mechanism for this kind of therapy has been elusive (Bickers, 1981; Pierach, 1982; Ryter and Tyrrell, 2000; Anderson et al, 2005; Bonkovsky, 2005; Solinas and Vajda, 2008; Cappellini et al, 2010; Puy et al, 2010; Siegesmund et al, 2010; Balwani and Desnick, 2012).…”

“…In fact, treatment with hemin can effectively cure these symptoms, although the underlying mechanism for this kind of therapy has been elusive (Bickers, 1981; Pierach, 1982; Ryter and Tyrrell, 2000; Anderson et al, 2005; Bonkovsky, 2005; Solinas and Vajda, 2008; Cappellini et al, 2010; Puy et al, 2010; Siegesmund et al, 2010; Balwani and Desnick, 2012). Our study reveals why the HEP fish produce lower levels of zymogens and how hemin restores production of these proteins (Fig.…”

“…A cascade of eight highly conserved enzymatic reactions controls heme biosynthesis (Kappas et al, 1995; Ryter and Tyrrell, 2000; Balwani and Desnick, 2012), and a group of rare and clinically complex diseases, known as porphyria, result directly from various genetic mutations that cause defective enzymes in the heme biosynthetic pathway (Kappas et al, 1995; Bonkovsky, 2005; Solinas and Vajda, 2008; Cappellini et al, 2010; Puy et al, 2010; Siegesmund et al, 2010; Balwani and Desnick, 2012). We have previously established a heme-deficient zebrafish that is homozygous for a mutation in uroporphyrinogen decarboxylase ( urod ; also known as yquem ) as a model for studying human hepatoerythropoietic porphyria (HEP) (Online Mendelian Inheritance in Man number 176100) and heme deficiency pathogenesis (Wang et al, 1998).…”

Hereditary coproporphyria from clinician’s point of view: A case report

“…Samo intravenska glukoza može se primeniti kod blažih napada ili dok se ne nabavi hem-arginat. Primenjuju se i lekovi (prema listi dozvoljenih) za uklanjanje simptoma akutnog napada [2][3][4][5]11,12].…”

Lack of Hemodynamic Effects After Extended Heme Synthesis Inhibition by Succinylacetone in Rats

“…Hypertension is a recognized outcome in HT, even in pediatric subjects (Strife et al, 1977;Gibbs et al, 1993;Klujber et al, 1997;Schlump et al, 2008), and remains an important diagnostic feature of the disease (Bonkovsky, 2005). We hypothesized that the accumulation of SA in type 1 HT may lead to cardiovascular hemoenzyme deficiency, thereby precipitating a hypertensive phenotype.…”