This is an autosomal dominant disorder with variable expressivity caused by partial (50%) deficiency in hydroxymethylbilane synthase. It has a prevalence of 1-3 in 100,000 but is much more common in certain parts of the world (Northern Sweden, Great Britain). Manifestations include colicky abdominal pain, vomiting, constipation, port wine-colored urine, and neurologic and psychiatric disturbances. Acute attacks rarely occur before puberty and may last from days to months. Photosensitivity does not occur. Clinical and biochemical manifestations may be precipitated by barbiturates, anticonvulsants, estrogens, oral contraceptives, the luteal phase of the menstrual cycle, alcohol, or low-calorie diets. Diagnosis is established by demonstrating elevation of urinary porphobilinogen (PBG) and 𝛄-aminolevulinic acid (ALA) during an acute attack. Genetic testing, if available, should be used to confirm the diagnosis.
Treatment: Acute Intermittent Porphyria As soon as possible after the onset of an attack, 3-4 mg of heme, in the form of heme arginate, heme albumin, or hematin, should be infused daily for 4 days. Heme acts by inhibiting ALA synthase, thereby restraining ALA and PBG production. Administration of IV glucose at rates up to 20 g/h or parenteral nutrition, if oral feeding is not possible for long periods, can be effective in acute attacks. Narcotic analgesics may be required during acute attacks for abdominal pain, and phenothiazines are useful for nausea, vomiting, anxiety, and restlessness. Treatment between attacks involves adequate nutritional intake, avoidance of drugs known to exacerbate the disease, and prompt treatment of other intercurrent diseases or infections. Liver transplantation has been effective in selected patient and gene replacement trials are underway. |
Section 13. Endocrinology and Metabolism