Acute Intermittent Porphyria

Excerpt

'Porphyria' has been derived from the ancient Greek word porphura, meaning purple. Porphyrins are precursors of heme, an essential component of hemoglobin. Each subunit of hemoglobin is a globular protein containing an embedded heme group that contains one iron atom, capable of binding one oxygen molecule. The heme synthesis pathway is a multi-step process that involves a specific enzyme at every step. Thus, porphyrias are distinct clinical syndromes, which arise due to deficiency or defect in a particular enzyme needed for a specific step of the heme synthesis pathway. Although these syndromes have conventionally been classified depending on the predominant system involved (cutaneous vs. neurohepatic), significant overlap occurs, and many porphyrias present with mixed symptoms.

The clinical presentation, severity, and prognosis of individual porphyrias depend on which enzyme is deficient and the corresponding heme precursor or porphyrin accumulation. Acute intermittent porphyria (AIP) ranks as the most common and severe form of acute porphyria. Other acute porphyrias include hereditary coproporphyria (HCP), variegate porphyria (VP), and 5-aminolevulinic acid (ALA) dehydratase deficiency porphyria (Doss porphyria).

Similar to the majority of porphyrias, AIP shows an autosomal dominant pattern of inheritance. Acute porphyrias like AIP characteristically demonstrate acute episodes of neurovisceral symptoms but may not manifest fully for a long time. AIP manifests as episodes of abdominal pain, neuropathies, and constipation, but, unlike most other porphyrias, patients with AIP do not develop a cutaneous rash. The primary enzymatic defect in AIP is the deficiency of porphobilinogen-deaminase, also called hydroxymethylbilane synthase (HMBS), the third enzyme in heme synthesis. The acute attacks of AIP are a result of the uncontrolled upregulation of the ALA synthase enzyme. The diagnosis of AIP gets delayed due to nonspecific symptoms and similarities with other diseases. The only cure is orthoptic liver transplantation.