vitamin-b-12 and Porphyria--Acute-Intermittent

Topics: Dietary Supplements; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Porphyria, Acute Intermittent; Vitamin B 12; Vitamins

Acute porphyrias (AP) are characterized by heme deficiency and induction of hepatic 5-aminolevulinate synthase (ALAS1). Hyperhomocysteinemia (HHcy) is associated with endothelial damage, neurotoxicity and increased risk for vascular diseases. Interestingly, both heme biosynthesis and sulphur amino acid metabolism require vitamin B6, (Pyridoxal-phosphate, PLP) an important cofactor of ALAS1 and of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGL) enzymes that catabolize homocysteine (Hcy). Moreover, heme itself is an important cofactor for CBS.. to assess plasma Hcy status and HHcy main determinants in patients with AP.. A total of 46 patients with AP (31 with Acute Intermittent Porphyria,15 with Variegate Porphyria) were assessed for clinical status (symptomatic vs. asymptomatic), serum Hcy, Cysteine (Cys), Vit.B6, Vit.B12, red blood cell folates and urinary delta-aminolevulinic acid (ALA) and porphobilinogen(PBG) levels (mean of six measurements).. Most patients with symptomatic AP present HHcy resulting from alterations in sulphur amino acid metabolism. HHcy may represent an indirect marker of ALAS1 induction and its prevalence may be suggestive of a role of HHcy in the pathogenesis and/or comorbidities of AP.

Topics: Cystathionine beta-Synthase; Homocysteine; Humans; Hyperhomocysteinemia; Porphyria, Acute Intermittent; Vitamin B 12

Homocysteine is an intermediate of methionine metabolism, and its elevation in tissues is correlated with an increased risk for vascular diseases. We measured homocysteine in plasma of 24 patients with acute intermittent porphyria (AIP) and long-term high excretion of heme precursors. Fifteen (62.5%) presented hyperhomocysteinemia (total homocysteine in plasma >15 μmol/L). No association was found between hyperhomocysteinemia and either urinary excretion of heme precursors or clinical status. All the patients showed normal levels of vitamin B₁₂ and folic acid, but 13 (54%) presented low plasma levels of pyridoxal 5'-phosphate (PLP <15 nmol/L). Cystathionine β-synthase (CBS) catalyzes a major removal pathway of homocysteine and is dependent on both PLP and heme as cofactors. It is hypothesized that, in AIP, CBS reduced hepatic activity resulting from either a low heme status and/or consumptive depletion of PLP due to increased demand by 5-aminolevulinatesynthase hyperactivity can induce hyperhomocysteinemia.

Topics: Adult; Female; Folic Acid; Humans; Hyperhomocysteinemia; Male; Middle Aged; Porphyria, Acute Intermittent; Pyridoxal Phosphate; Vitamin B 12

Topics: Corrinoids; Diagnosis, Differential; Edetic Acid; Hematinics; Humans; Neurotic Disorders; Porphyria, Acute Intermittent; Porphyrias; Prednisone; Prochlorperazine; Vitamin B 12

Topics: Chlorophyll; Cobalt; Hematinics; Humans; Iron; Porphyria, Acute Intermittent; Porphyrias; Vitamin B 12

Topics: Chlorophyll; Corrinoids; Hematinics; Humans; Neurologic Manifestations; Porphyria, Acute Intermittent; Porphyrias; Vitamin B 12