Abdominal Pain Case 1

A 27-year-old woman goes to an emergency room with severe abdominal pain. She had previously experienced similar episodes of pain that Iasted several hours to a few days, but this episode is the most severe. She has also been experiencing nausea, vomiting, and constipation.

The physician is left with the impression that she is agitated and somewhat confused, and an accurate history is difficult to elucidate. The patient is sent for emergency laparotomy, but no pathology is noted at surgery. Following the unrevealing surgery, an older surgeon comments that he had once seen a similar case that was actually due to porphyria.

Q 1

The porphyrias are biochemical abnormalities in which of the following pathways?

/ A. GIycogen degradation

/ B. Heme synthesis

/ C. Lipoprotein degradation

/ D. Nucleotide degradation

/ E. Urea cycle

Q 2

Following the surgery, the decision is made to screen for the porphyrias that cause acute neurovisceral symptoms. Which of the following

tests would be most likely to be used?

/ A. Erythrocyte porphyrins

/ B. Total fecal porphyrins

/ C. Total plasma porphyrins

/ D. Total urinary porphyrins

/ E. Urinary porphobilinogen

Q 3

Which of the following are the three most common forms of porphyria?

/ A. Acute intermittent porphyria, erythropoietic protoporphyria, and porphyria cutanea tarda

/ B. Acute intermittent porphyria, hepatoerythropoietic porphyria, and variegate porphyria

/ C. Congenital erythropoietic porphyria, delta-aminolevulinic acid dehydratase-deficient porphyria, and hepatoerythropoietic porphyria

/ D. Erythropoietic protoporphyria, hereditary coproporphyria, and porphyria cutanea tarda

/ E. Hereditary coproporphyria, variegate porphyria, and X-Iinked sideroblastic anemia

Q 4

This patient is found to have increased levels of both delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) in blood. Follow-up studies demonstrate low PBG deaminase in erythrocytes. AIso, additional history is elicited, revealing that the woman had started a very low carbohydrate diet about one week before being admitted to the hospitaI. Which of the following is the most likely diagnosis?

/ A. Acute intermittent porphyria

/ B. Congenital erythropoietic porphyria

/ C. Erythropoietic protoporphyria

/ D. Porphyria cutanea tarda

/ E. X-Iinked sideroblastic anemia

Q 5

Which of the following drugs would be most likely to induce an attack of abdominal pain in this patient?

/ A. Acetaminophen

/ B. Aspirin

/ C. Barbiturate

/ D. GIucocorticoid

/ E. Insulin

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Abdominal Pain Case 1 Answers:

A1

The correct answer is B. The porphyrias are a group of rare, related diseases that have in common a block in the heme synthesis pathway. The block is usually partial rather than complete, and thus many of these patients have only intermittent symptoms. Most cases of porphyria present with either a neurovisceral pattern (including both psychiatric symptoms and abdominal pain) or with photosensitive skin lesions. These two patterns are associated with different forms of porphyria.

Associate abnormalities of glycogen degradation (choice A) with the glycogen storage diseases, such as von Gierke disease, Pompe disease, and Forbes disease.

Associate abnormalities of lipoprotein degradation (choice C) with some forms of hyperlipoproteinemia (notably Type I).

Associate abnormalities of nucleotide degradation (choice D) with gout and Lesch-Nyhan syndrome.

Associate abnormalities of the urea cycle (choice E) with congenital hyperammonemia, citrullinemia, and argininosuccinic academia

A2

The correct answer is E. The acute neurovisceral porphyrias are those that tend to present with severe abdominal pain, often accompanied by neuropsychiatric symptoms. The best tests to use for screening of these diseases are urinary porphobilinogen (PBG, either random or 24 hour) and urinary delta-aminolevulinic acid (ALA, either random or 24 hour).

Erythrocyte porphyrins (choice A) are used for follow-up in the photosensitive types of porphyria.

Total fecal porphyrins (choice B) are used for follow-up evaluation after screening tests for either the photosensitive porphyrias or the acute neurovisceral porphyrias are positive.

Total plasma porphyrias (choice C) are useful for first line screening of the photosensitive porphyrias, and are used for further evaluation after screening in the acute neurovisceral porphyrias.

Total urinary porphyrins (choice D) are used for further evaluation after screening for acute neurovisceral porphyries

A3

The correct answer is A. The porphyrias are complex diseases that can easily appear overwhelming. A very useful point to know (both clinically and for the USMLE) is that the three most common forms are acute intermittent porphyria, erythropoietic protoporphyria, and porphyria cutanea tarda. Acute intermittent porphyria tends to present with acute neurovisceral symptoms. Erythrocytic protoporphyria tends to present acutely with painful skin lesions. Porphyria cutanea tarda tends to present with chronic blistering skin lesions. The other types listed in various choices are also porphyrias, but are less common.

A4

The correct answer is A. These laboratory findings are most consistent with acute intermittent porphyria, which is due to PBG deaminase deficiency. Patients usually, but not always, have a deficiency of erythrocyte PBG deaminases. (Some cases have also been described in which the enzyme deficiency is limited to liver.) The condition is an autosomal dominant disorder that typically becomes symptomatic in women after puberty, and then often only if a precipitating event (dieting, use of certain drugs, premenstrual) is also present. Symptoms during the attacks can include abdominal symptoms (pain, nausea, vomiting, constipation, diarrhea, abdominal distension, ileus), which are thought to be due to the effects of this condition on visceral nerves. Other symptoms that may be mediated neurologically include incontinence, urinary retention, tachycardia, diaphoresis, hypertension, muscle weakness, psychiatric symptoms, seizures, and rarely, severe paralysis, respiratory insufficiency, and death. Both intravenous glucose (oral is often inadequate due to poor intestinal function) and exogenous heme supplementation can suppress the heme biosynthetic mechanism, and tend to ameliorate the acute attack. Patients should be cautioned to diet gently, as intense dieting can precipitate attacks.

Congenital erythropoietic porphyria (choice B) is characterized by severe skin blistering that usually begins after birth, pink to dark-brown urine, normal ALA and PBG, and increased porphyrins (primarily uroporphyrin I and coproporphyrin I) in urine, plasma, and erythrocytes.

Erythropoietic protoporphyria (choice C) is characterized by cutaneous photosensitivity that begins early in life and high protoporphyrin in erythrocytes and bone marrow.

Porphyria cutanea tarda (choice D) is characterized by photosensitivity with skin blistering, elevated plasma porphyrins, and elevated urine porphyrins (mostly uroporphyrin and heptacarboxylporphyrin).

The very rare X-linked sideroblastic anemia (choice E), due to a deficiency of delta-aminolevulinic acid synthase, can clinically resemble acute intermittent porphyria, and is characterized by elevated levels of urinary ALA and coproporphyrin.

A5

The correct answer is C. Some symptomatic episodes of acute porphyria (including acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and aminolevulinic acid dehydratase porphyria) are triggered by drug ingestion, and administration of drugs to undiagnosed patients can cause an acute exacerbation of an ongoing attack of acute porphyria. Drugs considered unsafe for use in these patients notably include alcohol, anticonvulsants, barbiturates, many other sedatives, and sulfonamide antibiotics. Of particular concern are the sedative agents, since it may be very tempting to give an obviously agitated patient a sedative to allow easier examination of the patient. Many other drugs are also on the lists of potentially dangerous drugs in these patients. Once the diagnosis is established, the patient should be instructed to always inform her/his physician of her condition, and ask that the safety of drugs prescribed in patients with porphyria be checked. Many of the drugs that can induce or exacerbate an attack of porphyria do so by increasing the activity of the cytochrome P450 system, which indirectly triggers an increase in heme biosynthesis. The other medications listed in the choices are "safe" in these patients.