Child With Ataxia Telangiectasia Developing Acute Myeloid Leukemia

Abstract

An 11-year-old boy, who was diagnosed as having ataxia telangiectasia (AT) at 5 years of age, was referred to our hospital because of a right submandibular progressive enlarged mass for 2 months. He also suffered from being unstable to stand and recently had twisting of the trunk and tremor in all areas of his body. On physical examination, the patient looked pale and had multiple cervical lymphadenopathies and telangiectasia of the bulbar conjunctiva. His gums easily bled, and he had mild gingival hypertrophy. No hepatosplenomegaly or mucocutaneous petechiae were noted. Neurologic examination revealed nystagmus, squint, dysarthric speech, diminished reflexes, dysmetria, and ataxic gait. Laboratory investigations showed leukocytosis, anemia, and thrombocytopenia (WBC count 28,500/L; platelets 59,000/ L; hemoglobin 5.2 g/L; hematocrit 27.5%). Biochemistry tests revealed ALT of 27 U/L, AST of 29 U/L, blood urea nitrogen of 9 mg/dL, creatinine of 0.5 mg/dL, and lactate dehydrogenase of 352 U/L. The -fetoprotein level was high (242 ng/mL). There were decreased levels of immunoglobulin (Ig) A (6.67 mg/dL) and IgE ( 0.1 mg/dL). Electrophysiologic study showed mild to moderate motorpredominant spinal motor pathology with sensory involvement. Brain magnetic resonance images revealed isolated cerebellar atrophy with small size of vermis (Fig The ventricles were all normal. Analysis of the ATM gene revealed compound heterozygous mutation (2413 C to T, arg805ter; 1402-3 del AA, lys468fs). Bone marrow examination showed hypercellularity with an excess of blastic cells (80% to 85%) with primitive nuclear morphology, little cytoplasm, easily discernible nucleoli, and distinct nuclear membrane and markedly depleted hematopoietic cells (Fig These blasts were positive in peroxidase stain (Fig Flow cytometric analysis of the bone marrow aspirate revealed the following: CD13, 42.51%; CD33, 77.33%; CD34, 43.64%; HLA-DR, 34.71%; and negative for B-and T-cell markers. The karyotype of the bone marrow cells was 45,XY, 7, 10,t(12;14)(p11.2;q32), 14, 22. Acute myeloid leukemia (AML) was diagnosed. After AML was diagnosed, the patient received chemotherapy according to the Taiwan Pediatric Oncology Group AML-97A protocol. 1 Induction treatment consisted of cytarabine (100 mg/m 2 , continuous infusion, days 1 to 7) and idarubicin (9 mg/m 2 , intravenous push, days 1 to 3). Intrathecal methotrexate (15 mg) was administered on day 1. However, the patient did not achieve remission after two courses of induction therapy and consequently died as a result of severe pneumonia.