Porphyrias acute intermittent

If the enzyme lesion occurs early in the pathway prior to the formation of porphyrinogens (eg, enzyme 3 of Figure 32-9, which is affected in acute intermittent porphyria), ALA and PBG will accumulate in body tissues and fluids (Figure 32-11). Glinically, patients complain of abdominal pain and neuropsychiatric symptoms. The precise biochemical cause of these symptoms has not been determined but may relate to elevated levels of ALA or PBG or to a deficiency of heme. 

ALA dehydratase deficiency (hepatic) (MIM 125270) Acute intermittent porphyria (hepatic) (MIM 176000) Congenital erythropoietic (erythropoietic) (MIM 263700)... 

Acute intermittent porphyria is a dominantly inherited partial deficiency of porphobilinogen deaminase, and causes axonal polyneuropathy. Acute intermittent porphyria is caused by partial deficiency of porphobilinogen deaminase, an enzyme required for heme biosynthesis. Patients may present with acute abdominal pain, rapidly progressive sensorimotor axonal polyneuropathy or psychosis, and have elevated concentrations of the heme precursor 8-amino-levulinic acid in their urine. Symptoms may be precipitated by treatment with barbiturates or other drugs and are suppressed by treatment with hematin [59]. 

Floderus, Y., Shoolingin-Jordan, R M. and Harper, P. Acute intermittent porphyria in Sweden. Molecular, functional and clinical consequences of some new mutations found in the porphobilinogen deaminase gene. Clin. Genet. 62 288-297, 2002. 

Acute Intermittent Porphyria Uroporphyrinogen-I Synthase Deficiency... 

A 48-year-old man developed abdominal colic, muscle pain, and fetigue. Following a 3-week hospitalization, acute intermittent porphyria was initially diagnosed based on a high level of urinary 5-aminolevulinic acid. Subsequent analysis of the patient s circulating red blood ceUs revealed that 70% contained elevated levels of zinc protoporphyrin, and the diagnosis was corrected. The correct diagnosis is most likely to be... 

Although normally present in normal human plasma in abundance ( 0.6 mg/ml, 10 pM) (27-30), concentrations ofhemopexin are sensitive to a variety of pathological conditions. Decreased levels have been noted in chronic and severe hemolytic states (31) and in heme infusion of acute intermittent porphyria patients (32). On the other hand, hemopexin levels increase in the acute-phase response (33-36), and hemopexin has been designated as a type II acute-phase reactant. Plasma hemopexin also increases in certain conditions of muscle breakdown and neuromuscular disease (37). 

Acute intermittent porphyria Estrogens have been reported to precipitate attacks of acute intermittent porphyria. 

Porphyria Danazol administration has been reported to cause exacerbation of the manifestations of acute intermittent porphyria. 

Acute intermittent porphyria allergic or idiosyncratic reactions to meprobamate or... 

Acute agitation associated with bipolar I mania Acute agitation in schizophrenia Acute intermittent porphyria... 

Porphyria, acute Intermittent - For the treatment of acute intermittent porphyria. 

Acute intermittent porphyria (adults) - 25 to 50 mg orally 3 or 4 times/day or 25 mg IM 3 or 4 times/day until patient can take oral therapy. 

Acute intermittent porphyria Administer hydantoins cautiously to patients with acute intermittent porphyria. 

Acute intermittent porphyria or glucose-6-phosphate dehydrogenase deficiency Use with caution in patients with acute intermittent porphyria or glucose-6-phosphate dehydrogenase deficiency. 

This group includes acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria. 

Most of the adverse reactions associated with the use of the intravenous barbiturates are predictable and therefore can be controlled or avoided. Some reactions, such as hypersensitivity, are entirely unpredictable. Particularly patients with asthma, urticaria, or an-gioedema may acquire allergic hypersensitivity to the barbiturates. Acute intermittent porphyria is an absolute contraindication to the use of barbiturates. 

Griseofulvin is usually well tolerated. Headache is common with initiation of therapy. Hepatotoxicity (especially in patients with acute intermittent porphyria), dermatitis, and gastrointestinal distress also occur. Griseofulvin increases warfarin metabolism, and griseofulvin metabolism is increased by phenobarbital. 

Contraindications Acute intermittent porphyria, sensitivity to meprobamate, meb-utamate, ortybamate... 

Contraindications Acute intermittent porphyria, hypersensitivity to meprobamate or related compounds... 

Adverse effects include laryngospasm, which occurs generally when respiratory secretions or other irritants are present. Shivering and delirium may occur during recovery. Postoperative pain induces restlessness. Nausea and vomiting are uncommon. It can precipitate acute intermittent porphyria in susceptible individuals. 

Barbiturates may precipitate episodes of acute intermittent porphyria (AIP) and their use is contraindicated in patients who are predisposed to this condition. Some animal models indicate that ketamine, etomidate, and the benzodiazepines may be porphyrinogenic and propofol is considered to be the intravenous anaesthetic of choice in AlP-prone patients. 

Idio ncrasy. This is a response that is qualitatively different from the action of the drug in normal individuals, again often genetically determined. Of importance to anaesthetists are abnormal responses to several drugs in patients with acute intermittent porphyria, and in those susceptible to the malignant hyperpyrexia syndrome. 

Barbiturates reduce hepatic blood flow and glomerular filtration rate, but these drugs produce no adverse effects on hepatic or renal function. Barbiturates can exacerbate acute intermittent porphyria by inducing the production of hepatic ct -aminolevulinic acid (ALA) synthase (see Chapter 22). On rare occasions, thiopental has precipitated porphyric crisis when used as an induction agent in susceptible patients. 

Individuals affected with porphyria present with acute attacks, skin lesions, or both. The onset of these attacks rarely occurs before puberty. An attack usually consists of severe abdominal pain and often neurological sequelae. During and after such attacks, excessive amounts of aminolevulinic acid and PBG are excreted in the urine. The most common porphyria is PBG deaminase deficiency (acute intermittent porphyria), which primarily affects liver function. A positive result coupled with a clinical indication of hepatosplenomegaly suggests that evaluation for tyrosine metabolites in the urine should be pursued (using the nitrosonaphthol test). 

Grandchamp B, Picat C, Mignotte V, Wilson JH, Velde K, Sandkuyl L, Romeo PH, Goos-sens M, Nordmann Y (1989) Tissue-specific splicing mutation in acute intermittent porphyria. Proc Natl Acad Sci USA 86 661-664... 

Minder El (1993) Coproporphyrin isomers in acute-intermittent porphyria. Scand J Clin Lab Invest 53 87-90... 

Hift RJ, Meissner PN (2005) An analysis of 112 acute porphyric attacks in Cape Town, South Africa. Evidence that acute intermittent porphyria and variegate porphyria differ in susceptibility and severity. Medicine 84 48-60... 

Schuurmans MM, Schneider-Yin X, Rufenacht UB, Schnyder C, Minder CE, Puy H, Dey-bach JC, Minder El (2001) Influence of age and gender on the clinical expression of acute intermittent porphyria based on molecular study of porphobilinogen deaminase gene among Swiss patients. Mol Med 7 535-542... 

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