Review Question - QID 214381

This patient has pancytopenia, developmental delay (he speaks in 2-word phrases, suggesting a 2-year-old's language ability), and visible congenital anomalies including short stature, hypoplastic thumbs, and multiple café-au-lait spots (flat, brown patches with irregular edges) which is consistent with Fanconi anemia.

Fanconi anemia is caused by a genetic DNA repair defect that leads to impaired hematopoiesis. Patients typically present between 4-12 years with signs of thrombocytopenia such as petechiae, bruising, and bleeding, followed by leukopenia and anemia. Children with Fanconi anemia have characteristic congenital anomalies including abnormal thumbs, short stature, abnormal skin pigmentation, café-au-lait spots, genitourinary anomalies, skeletal abnormalities of the limbs, and heart defects. The diagnosis is confirmed with a positive chromosome breakage test, and treatment consists of a hematopoietic stem cell transplant.

Incorrect Answers:
Answer 1: Alterations in ribosomal protein genes cause Diamond-Blackfan anemia, an autosomal dominant pure red cell aplasia. Diamond-Blackfan anemia presents with anemia and congenital anomalies such as short stature, craniofacial defects, and abnormalities of the upper limbs. However, unlike Fanconi anemia, the anemia often comes on rapidly in the first year of life.

Answer 2: Decrease in DNA synthesis due to homocysteine accumulation is the mechanism behind the megaloblastic anemia caused by vitamin B12 deficiency. Vitamin B12 is a cofactor for methionine synthase, an enzyme that converts homocysteine to methionine and produces THF, an intermediate for pyrimidine synthesis. Vitamin B12 deficiency typically presents with macrocytic anemia, glossitis, peripheral neuropathy, and neuropsychiatric issues.

Answer 3: Deficiency of glucocerebrosidase enzyme is the mechanism behind Gaucher disease, an autosomal recessive condition. Because the glucocerebrosidase enzyme is deficient, glucocerebroside, a lipid with a glucose head group, builds up in the spleen, liver, kidneys, lungs, brain, and bone marrow. Gaucher disease thus presents with anemia, thrombocytopenia, hepatosplenomegaly, bone pain, and failure to thrive.

Answer 5: Increased production of reactive oxygen species is one of the mechanisms that lead to the symptoms of chronic lead poisoning. Lead can generate reactive oxygen species that then damage DNA and cellular membranes and disrupt DNA transcription and multiple cellular enzymes. Chronic lead poisoning in children can present with behavioral problems, mood lability, developmental delays, hand and foot drop, and mild, microcytic anemia.

Bullet Summary:
Fanconi anemia is a genetic DNA repair defect that presents with pancytopenia, congenital anomalies, and developmental delay in children between ages 4-12.