Review Question - QID 216652

This infant who presents with macrocytic anemia, low reticulocyte count, and triphalangeal thumb on physical examination likely has Diamond-Blackfan anemia.

Diamond-Blackfan anemia is a genetic disorder caused by a defect in ribosome production. It usually presents within the first year of life with anemia and lab results showing pure red cell aplasia (isolated anemia with reticulocytopenia). Presenting symptoms include fatigue and poor feeding. Physical exam reveals numerous abnormalities including microcephaly, atrial and ventricular septal defects, and triphalangeal thumb. Many patients become dependent on steroids for treatment. It is also common for patients to require regular blood transfusions. Rarely, spontaneous remission has been reported in this condition.

Figure/Illustration A is an image of a hand showing a triphalangeal thumb (arrow), a congenital malformation in which the thumb has 3 phalanges instead of 2. This malformation is seen in various syndromes including Diamond-Blackfan anemia.

In their review, Lipton et al. discuss the diagnosis of Diamond Blackfan anemia. They report that impaired ribosome biogenesis resulting in pro-apoptotic erythropoiesis is hypothesized to underly the pathogenesis of the disease. It is recommended to consider the constellation of symptoms when making the diagnosis.

Incorrect Answers:
Answer 1: Aplastic anemia occurs when the bone marrow fails to produce blood cells of all types due to a hereditary or immune disease or due to exposure to chemicals, drugs, or radiation. It would present with anemia but also with other reduced cell counts such as thrombocytopenia. Symptoms of aplastic anemia include fatigue, pallor, and recurrent infections.

Answer 3: Fanconi anemia is a congenital cause of anemia that usually presents later in childhood, and is associated with abnormalities in other cell lines such as thrombocytopenia. It can also present with other abnormalities including cafe-au-lait spots and strabismus.

Answer 4: Hemolytic disease of the newborn occurs when IgG molecules against red blood cells pass from the mother through the placenta to a newborn due to incompatibility of blood types. Hemolytic disease of the newborn would not present with triphalangeal thumbs, and other signs such as jaundice, kernicterus, and hepatosplenomegaly would be seen.

Answer 5: Vitamin B12 deficiency may present with a macrocytic anemia in patients with severe malnutrition and is more common in the elderly, patients with alcohol use disorder, and patients with terminal ileum resection or dysfunction (such as Crohn disease). However, triphalangeal thumbs are not seen in this disorder and focal neurologic deficits, such as impaired sense of proprioception and vibration, would be apparent.

Bullet Summary:
Diamond-Blackfan anemia is a congenital cause of pure red cell aplasia and is associated with triphalangeal thumbs.