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Acute Intermittent Porphyrias Introduction PART 2

Porphyrias are inherited and/or acquired disorders of heme biosynthesis. A review article published in the March 2005 Annals of Internal Medicine (1) provides expert recommendations on the diagnosis and treatment of the acute porphyrias, which are the most life-threatening of the porphyrias. In addition, two valuable websites are available as resources for the ER physician:
Heme is synthesized in all tissues in eight enzymatic steps, and the end product is a component of many essential hemoproteins, such as hemoglobin, myoglobin and cytochromes, including the cytochrome P450 enzymes (CYPs) that are especially abundant in the liver. The first enzyme, ALA synthase (ALAS), controls the rate of heme synthesis in the liver. This enzyme is down-regulated by heme. The four acute hepatic porphyrias are due to different enzyme deficiencies (Table 1). The most common of these is acute intermittent porphyria (AIP), but the others can produce the same neurovisceral symptoms. The enzyme deficiency limits the capacity of the liver to increase heme synthesis. Therefore, when drugs, hormones or other factors that induce ALAS and CYPs are given, ALA and porphobilinogen (PBG) are overproduced and accumulate, and a neurovisceral attack may develop (2). Both ALA and porphobilinogen (PBG) increase during attacks of AIP, hereditary coproporphyria (HCP) and variegate porphyria (VP), although these increases may be less and more transient in HCP and VP. Increases in porphobilinogen (PBG) are generally greater than ALA. In ADP, which is extremely rare, only ALA is increased. Increases in urinary porphyrins also occur in these conditions, but are less specific because they also increase in many other medical conditions.

Gastrointestinal symptoms: 
Acute abdominal pain occurs in about 85-90% of attacks (1), and is neurologic in origin. The pain is usually severe, diffuse, unremitting for hours and poorly localized, but is sometimes colicky. Nausea, vomiting and constipation are common, but diarrhea is sometimes noted.
Neurologic symptoms:
Pain in the extremities, back, chest or head is also common. Objective sensory loss may be found in up to 40% of cases (1). Peripheral motor neuropathy is an indication of a severe and potentially life-threatening attack. Neuropathy can progress to respiratory failure and bulbar paralysis in hours or days. Sudden death, presumably from cardiac arrhythmia may occur. Bladder paresis may cause dysuria and hesitancy (1).
The central nervous system is also affected. For example, insomnia is often an early symptom. Agitation, confusion, combativeness and other acute neuropsychiatric features are common and sometimes progress to coma. Convulsions may result from porphyria itself or from hyponatremia.
Physical findings:
Tachycardia and systemic hypertension are very common. Fever is absent or mild. Signs of peritoneal irritation, such as tenderness are usually not prominent, but there is often ileus with distension and decreased bowel sounds. However, at times bowel sounds are normal or increased.
Motor weakness, which is usually symmetrical and begins proximally in the upper extremities, can be difficult to detect because common tests of strength, such as hand-grip, are not initially affected.
Clinical laboratory tests:
Leukocytosis is usually absent or mild. Hyponatremia may reflect inappropriate antidiuretic hormone secretion. Gastrointestinal or renal sodium loss may contribute.
Sensitive and specific laboratory tests are available for diagnosis of acute porphyrias, especially during acute attacks, as described below.


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