A 26-year-old woman is evaluated in the ER for diffuse abdominal pain and nausea. The pain started 1 day ago and is currently at its maximum intensity. She denies fever but has noticed constipation and dark urine. She had similar episodes in the past and underwent appendectomy and cholecystectomy on two different occasions. On physical examination, she is tachycardic with diffuse abdominal tenderness but no rebound tenderness. Her bowel sounds are slightly sluggish. On neurological examination, she has decreased sensation to fine and crude touch in both lower extremities up to her knees. Her hemoglobin, WBC, and platelet count are normal. She has mild transaminitis with alanine transaminase (ALT) 123 IU/L, aspartate transaminase (AST) 160 IU/L, and alkaline phosphatase (ALP) 122 IU/L. Urine is red but urine dipstick is negative for blood, leukocyte esterase, nitrite, glucose, or protein. Urine porphobilinogen and total porphyrin level are elevated, plasma porphyrin level is normal. What is the most likely explanation of her recurrent symptoms?
Acute intermittent porphyria (AIP) is a disorder of heme biosynthetic pathway due to a deficiency in the enzyme porphobilinogen deaminase. Since the biosynthetic pathway cannot move forward due to defective enzyme activity, accumulation of the upstream substrate delta-aminolaevulinic acid and porphobilinogen cause various clinical manifestations including abdominal pain, nausea, vomiting, peripheral neuropathy, neurogenic bladder, tachycardia, hypertension, and tremor during acute attack. Since the pain is neurogenic, and not due to infection or inflammation, rebound tenderness, leukocytosis, and fever are uncommon. Patients may have mild hepatic dysfunction with slight elevation of ALT and AST. Both serum and urine porphobilinogen and delta-aminolaevulinic acid are elevated during an acute attack. Fecal porphyrins are normal. Many factors are known to cause acute exacerbation of AIP. Drugs such as phenytoin, barbiturates, alcohol, starvation or reduced carbohydrate intake, and stress can cause exacerbation.Porphyria cutanea tarda is due to an acquired deficiency of hepatic enzyme uroporphyrinogen decarboxylase. A chronic blistering skin condition is highly characteristic of this porphyria. Urinary delta-aminolaevulinic acid and porphobilinogen excretion may be normal or slightly elevated. Alcoholism and iron overload are frequently found to be exacerbating factors.Variegate porphyria (VP) is due to the deficiency of protoporphyrinogen oxidase, which is a mitochondrial enzyme in heme biosynthetic pathway. Patients may present with symptoms of acute intermittent porphyria, cutaneous blistering porphyria, or both. Plasma and fecal total porphyrin determinations are most useful in distinguishing VP and AIP since they are elevated in VP but not in AIP.Thalassemia syndromes constitute a heterogeneous group of genetic disorders, the clinical manifestations of which result from decreased or absent production of normal globin chains of hemoglobin. These abnormalities result in hypochromic, microcytic anemias of varying severity.Urine porphobilinogen and total porphyrin level are not elevated in any form of thalassemia. Autoimmune hepatitis could cause the transaminase elevation but would not account for the recurrent bouts of abdominal pain, the peripheral neuropathy, or the red urine.
Variegate porphyria
Thalassemia
Acute intermittent porphyria
Porphyria cutanea tarda
Oncology