A triad of the following symptoms: visceral abdominal pain, neurological dysfunction, and psychiatric disturbances suggest acute porphyria. ![]() ĭue to the significant degree of overlap with other conditions and varied range of presentation, it is essential to have a high index of suspicion when making the diagnosis. The skin lesions include bullous-type lesions and erosions occurring in sun-exposed areas. Ĭutaneous manifestations may be found with certain types of acute porphyrias such as variegate porphyria and HCP. Evidence of peripheral neuropathy is common in acute hepatic porphyrias. Motor paresis or poor respiratory effort may be present. On examination, the patient may be hypertensive with tachycardia or have evidence of arrhythmias. It is best to refer to the website: for details. History of recent alcohol intake is also important to note as reports exist of this as a trigger factor for acute attacks. Online drug databases that provide information about the safety of different drugs in porphyria are available. A family history of porphyrias, use of hormonal therapy, and menstrual history in females are also important to elicit on history taking. The patient may also report darkening of the urine (red color), particularly on exposure to light.ĭetailed drug history is essential to exclude the intake of precipitating agents. The most frequent cause of admission in acute porphyria is acute abdominal pain. Psychiatric manifestations, which are present in up to 80% of acute attacks, include behavior change, agitation, depression, hallucinations, altered mental status, and acute psychosis. Acute attacks typically consist of severe abdominal pain, nausea, constipation, palpitations, sweating, confusion, and other neurological manifestations such as peripheral neuropathy, seizures, and paresis, tachycardia, and hypertension. Attacks in females often have associations with the onset of menstruation. Patients present initially in adolescence or young adulthood. One hypothesis is that the deficiency of heme affects neuronal function the other hypothesis is that the precursors aminolevulinic acid (ALA) and porphobilinogen PBG may have direct neurotoxic effects. ![]() The pathogenesis of neurovisceral symptoms in acute porphyria has not been fully elucidated. The rarest acute porphyria, which is caused by a defect in the enzyme ALA dehydratase, is known as delta-aminolevulinic aciduria or ALA dehydratase deficiency (ALAD) and has an autosomal recessive inheritance pattern. AIP, VP, and HCP have a 50% deficiency of the respective enzymes and show low penetrance thus, around 90% of heterozygotes are asymptomatic for life. The enzyme affected is porphobilinogen (PBG) deaminase also referred to as Hydroxymethylbilane synthase (HMBS.) Hereditary coproporphyrin (enzyme defect coproporphyrinogen oxidase) and variegate porphyria (enzyme defect protoporphyrinogen oxidase) are also autosomal dominant inherited porphyrias and both present with cutaneous manifestations. The most common acute porphyria is acute intermittent porphyria (AIP). AIP is an autosomal dominant acute hepatic porphyria. The liver is the source of the four acute porphyrias and also to one of the cutaneous porphyrias (PCT). The enzyme deficiencies are inherited as either autosomal dominant (AD), autosomal recessive (AR), or less commonly as X- linked. Porphyrias fall into two classes: either erythropoietic or hepatic forms depending on the site of the major enzyme deficiency. ![]() The last step is the conversion of this to heme in the presence of iron by ferrochelatase. The enzyme ALA dehydratase then catalyzes the conversion of ALA to porphobilinogen (PBG). Porphobilinogen deaminase converts PBG to hydroxymethylbilane. Uroporphyrinogen converts this to uroporphyrinogen III, which is then acted upon by uroporphyrinogen decarboxylase to form coproporphyrinogen-III this undergoes oxidation to protoporphyrinogen IX. The rate-limiting enzyme in the formation of heme is the hepatic ALA synthase1 enzyme, which heme inhibits. The pathway consists of 8 enzymatic steps, four enzymes are present in the cytosol, and four enzymes are present in the mitochondria. The heme biosynthetic pathway involves the conversion of the substrates glycine and succinyl coenzyme A to heme. Heme is a 64 kDa tetrameric protein present in hemoglobin, myoglobin, respiratory cytochromes, and cytochrome P450 enzymes.
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