Abstract 37 Allergy, Immunology, and Rheumatology Poster Symposium, Sunday, 5/2

We describe 2 children studied at our institution in the last 3 years who share distinctive physical, hematologic and immunologic abnormalities.

Case 1 was a male infant born at 27 weeks gestation. The pregnancy was complicated by oligohydramnios and intrauterine growth retardation. At 3 months of age he remained hospitalized because of acquired pancytopenia, poor growth, and hypertension. He was found to have bilateral basal ganglia calcifications. No congenital infection could be identified. A bone marrow aspirate (BMA) showed severe hypoplasia of all cell lines. Serum IgG was 91 and IgM <4 ug/ml. His absolute CD4 count was 604 (71%) and CD8 count 221/ul (26%). CD19+/CD3- B cells were absent and surface expression of immunoglobulin was not detected. T cell proliferation in response to mitogens was normal. Proliferative responses to Candida were subnormal. Anti-neutrophil and anti-platelet antibodies were not detected. Intravenous immunoglobulin (IVIG) therapy did not affect his pancytopenia. Neutropenia improved with administration of G-CSF, however the patient continued to require red cell and platelet transfusions and expired at 5 months of age.

Case 2 is a girl born at term following an uncomplicated pregnancy. In the first year of life she had poor growth and moderate developmental delay and was found to have hydrocephalus and bilateral basal ganglia calcifications. An extensive evaluation for congenital infections was negative. She had multiple episodes of otitis media and pneumonia. She was admitted to hospital at 19 months of age with the new onset of pancytopenia, otitis media and polymicrobial bacteremia. BMA showed hypoplasia of all cell lines. Serum IgG was 33, IgA 7 and IgM 13 mg/ml. Her absolute CD4 count was 1571 (61%) and CD8 count 957/ul(37%). Her absolute CD19+/CD3- cell count was 31/ul (1%) with 0- 1% of cells positive for surface immunoglobulin. T cell proliferation in response to ConA, PHA, tetanus toxoid and Candida were normal, whereas PWM responses were low. Anti-neutrophil and anti-platelet antibodies were not detected. Following treatment with IVIG and G-CSF she remains clinically well with persistent moderate pancytopenia.

No evidence of congenital infection was found in either patient. No other family members were reported to have similar medical problems and both patients had healthy older female siblings. This unusual constellation of findings suggests a new syndrome, with possible autosomal recessive inheritance. The incidence of this disorder is unknown, but our identification of 2 subjects in a relatively short period of time suggests that it may not be extremely rare. Children with growth failure, intracranial calcifications, and hematologic abnormalities are frequently evaluated for congenital infections. Our experience suggests that immunologic assessment of these children is also indicated.