A 15-year-old boy is brought to his pediatrician for a follow-up visit. His parents report that he is doing well in school and has many friends. Their only concern is that he has a “difficult stomach.” Every few months, he complains of intermittent abdominal pain that takes several days to pass. He occasionally misses school due to the pain. There is blood in his stool during these episodes. These symptoms have persisted for many years. The parents have so far managed the condition using herbal teas and essential oils but have not sought formal medical care. His temperature is 98.2°F (36.8°C), blood pressure is 106/61 mmHg, pulse is 88/min, and respirations are 12/min. He has lost 10 pounds since his annual visit the year before and is the same height. On physical exam, the patient is thin with conjunctival pallor. His sclerae are anicteric and his abdomen is soft and non-tender without hepatosplenomegaly. He also has the findings seen in Figure A. He undergoes an abdominal CT that shows disease affecting the terminal ileum. Which of the following is most likely to be present in this patient?
Increased serum methylmalonic acid level
Microcytes
Decreased serum homocysteine level
Prolonged partial thromboplastin time
Increased serum methylmalonic acid level
This patient with episodic abdominal pain, bloody stool, growth failure, and erythema nodosum most likely has Crohn disease. Disease involving the terminal ileum predisposes patients to vitamin B12 deficiency, which would cause anemia with an elevated serum methylmalonic acid level.

Crohn disease is an inflammatory bowel disease that presents with abdominal pain, bloody stools, and growth failure in children. Extra-intestinal manifestations of Crohn disease include fistula formation and erythema nodosum, which appear as multiple tender erythematous nodules that fade after 1-2 weeks into bluish plaques or macules that can be confused with bruises. Complications of Crohn disease when the disease involves the terminal ileum is vitamin deficiency and malabsorption. These deficiencies can include vitamin A, vitamin D, vitamin E, vitamin K, zinc, and vitamin B12. Vitamin B12 deficiency presents with a macrocytic, megaloblastic anemia with hypersegmented neutrophils on peripheral blood smear. Lab findings include elevated serum homocysteine and methylmalonic acid levels. Vitamin B12 deficiency is also associated with peripheral neuropathy and should be treated with intramuscular vitamin repletion.

Akbulut presents the current state of evidence regarding vitamin deficiency in patients with Crohn disease. They found that vitamin B12 and folate levels are often low in patients with this disease. They recommend monitoring vitamin levels and providing repletion when necessary.

Figure/Illustration A is a clinical photograph showing erythematous nodules on the extensor surfaces of the legs (red circles). This finding is consistent with the latter stage of erythema nodosum.

Incorrect Answers:
Answer A: Decreased mean corpuscular volume may be seen in iron deficiency anemia, which can be co-morbid with Crohn disease. While this patient does have recurrent gastrointestinal blood loss, the very low frequency of his symptoms is unlikely to result in iron deficiency, making a decreased MCV less likely compared to an increased MCV given the underlying terminal ileum pathology.

Answer B: Decreased serum homocysteine level is not seen in any common human disease. An elevated (not decreased) serum homocysteine level is seen in vitamin B12 deficiency in addition to folate deficiency. This increase is due to the impaired processing of homocysteine in the absence of these cofactors.

Answer D: Microcytes would not be seen in vitamin B12 deficiency or folate deficiency, which instead present with macro-ovalocytes. Microcytic anemia would be seen in patients with iron deficiency anemia, which can present with fatigue and pallor in patients with occult bleeding. Iron supplementation and treatment of the underlying source of bleeding is appropriate care.

Answer E: A prolonged PTT could be seen in this patient as vitamin K absorption is likely affected. This patient is not presenting with a chief complaint of bruising/bleeding (the physical exam finding is erythema nodosum rather than ecchymosis), and symptoms point toward a diagnosis of anemia which would be associated with poor B12 absorption.

Bullet Summary:
Crohn disease may affect the terminal ileum, resulting in vitamin B12 deficiency (increasing the serum methylmalonic acid level) that would present with macrocytic, megaloblastic anemia with hypersegmented neutrophils on a peripheral blood smear.