The acute hepatic porphyrias (AHPs) are a group of four inherited diseases of heme biosynthesis that present with episodic, acute neurovisceral symptoms. The four types are 5‐aminolevulinic acid (ALA) dehydratase deficiency porphyria, acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria. Their diagnoses are often missed or delayed because the clinical symptoms mimic other more common disorders. Recent results indicate that acute intermittent porphyria, the most severe of the more common types of AHP, is more prevalent than previously thought, occurring in about 1 in 1600 Caucasians, but with low clinical penetrance (approximately 2%‐3%). Here we provide an updated review of relevant literature and discuss recent and emerging advances in treatment of these disorders. Symptomatic attacks occur primarily in females between 14 and 45 years of age. AHP is diagnosed by finding significantly elevated levels of porphyrin precursors ALA and porphobilinogen in urine. Acute attacks should be treated promptly with intravenous heme therapy to avoid the development of potentially irreversible neurologic sequelae. All patients should be counseled about avoiding potential triggers for acute attacks and monitored regularly for the development of long‐term complications. Their first‐degree relatives should undergo targeted gene testing. Patients who suffer recurrent acute attacks can be particularly challenging to manage. Approximately 20% of patients with recurrent symptoms develop chronic and ongoing pain and other symptoms. We discuss newer treatment options in development, including small interfering RNA, to down‐regulate ALA synthase‐1 and/or wild‐type messenger RNA of defective genes delivered selectively to hepatocytes for these patients. We expect that the newer treatments will diminish and perhaps obviate the need for liver transplantation as treatment of these inborn metabolic disorders.

A n 18-year-old woman from rural Minnesota was admitted to the hospital after presenting to a local emergency department with a 3-day history of severe right upper quadrant abdominal pain and a 2-week history of headaches, fever, nausea, and vomiting. A review of systems was otherwise unrevealing. Her only medication was trimethoprim-sulfamethoxazole for a recent urinary tract infection. She had no other notable medical history. She reported rare alcohol use 3 years previously and no recent use of over-the-counter medications or dietary supplements, smoking, illegal drug use, or sexual activity. Physical examination findings and vital signs were unremarkable aside from a temperature of 39.0°C and right upper quadrant tenderness without rebound or guarding. There was no hepatosplenomegaly or flank dullness.Laboratory studies revealed the following (reference ranges shown parenthetically): alkaline phosphatase, 738 U/L (52-144 U/L); aspartate aminotransferase (AST), 285 U/L (8-43 U/L); alanine aminotransferase (ALT), 417 U/L (7-45 U/L); total bilirubin, 2.3 mg/dL (0.1-1.0 mg/dL); direct bilirubin, 1.2 mg/dL (0.0-0.3 mg/dL); and platelet count, 101 ϫ 10 9 /L (150-450 ϫ 10 9 /L). Her hemoglobin level, leukocyte count, urinalysis results, and amylase, lipase, lactate, electrolyte, and serum creatinine levels were all within normal limits. Results of serologies for acute hepatitis A, B, and C, a heterophile antibody test, and a pregnancy test were negative, and salicylate and acetaminophen levels were unremarkable.

A 65-year-old woman presented with a 5-month history of nausea, vomiting, and weight loss. Prior esophagogastrodudenoscopy showed retained food and delayed gastric emptying, but abdominal computed tomography was normal. The working diagnosis was idiopathic gastroparesis. Subsequently, an electrogastrogram test showed normal 3-cycle-per-minute activity, although it was suggestive of obstructive gastroparesis. Repeat esophagogastrodudenoscopy showed obstruction at the postbulbar duodenum. Repeat abdominal computed tomography revealed a 2.2 x 1.6-cm mass in the pancreaticoduodenal groove narrowing the descending duodenum and aspiration of the mass revealed adenocarcinoma.

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