Acute intermittent porphyria

INTRODUCTION

Acute intermittent porphyria (AIP) is both the most common and most severe of the inherited porphyrias. It is an autosomal dominant disorder resulting from a partial deficiency of porphobilinogen deaminase (PBGD) activity, the third enzyme in the pathway of heme synthesis (figure 1 and algorithm 1), step 3). It is also called Swedish porphyria, pyrroloporphyria, or intermittent acute porphyria.

The incidence, pathophysiology, diagnosis, and treatment of AIP will be reviewed here. A general approach to the porphyrias is presented separately. (See "Porphyrias: An overview".)

PATHOPHYSIOLOGY

The majority of patients with AIP show deficient PBGD activity (approximately 50 percent of normal) in all tissues, including erythrocytes. However, a subset of patients (≤5 percent) show deficient enzyme activity only in nonerythroid cells (see below) [1].

Approximately 90 percent of individuals with this inherited enzyme deficiency remain biochemically and clinically normal throughout life. Clinical expression of the disease is usually linked to factors that stimulate or derepress the activity of the nonspecific delta-aminolevulinic acid synthase (ALAS1 or ALAS-N) in the liver (see below). These can be environmental or acquired factors, such as nutritional status (eg, fasting, starvation), drugs, steroids, and other chemicals of endogenous or exogenous origin (algorithm 2).

The cardinal pathologic changes seen in AIP result in neurologic dysfunction, which can affect the peripheral, autonomic, and/or central nervous systems, leading to multiple "neurovisceral" complaints (table 1) [2]. Unlike the cutaneous erythropoietic porphyrias in which there is porphyrin accumulation in tissues, AIP is not associated with cutaneous photosensitivity, since only the photodynamically inactive porphyrin precursors porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) accumulate.