Colitis associated with deficiency of the sixth component of complement and congenital chronic neutropenia

Sir, A deŽ ciency of the sixth component of complement (C6 deŽ ciency) characterized by invasive neisserial infection is unusual in Japan (1). Congenital neutropenia is a rare condition which is caused by many aetiologies and results in frequent bacterial infections (2). We report on a case of C6 deŽ ciency and congenital chronic neutropenia, with colitis. A Japanese infant, the second son of consanguineous parents, had a normal delivery at 37 wk gestation, birthweight 2.57 kg, but at day 1 of age, he was admitted to our neonatal intensive care unit because of sepsis caused by Staphylococcus aureus. Laboratory data were: haemoglobin 155 g/L; white blood cells 2.06 10/L with 8% band forms, 10% segmented neutrophils, 17% monocytes, and 65% lymphocytes; platelets 223 10/L. The patient recovered from the sepsis after a course of antibiotics, but neutropenia (range 0.5– 1.0 10/L) persisted despite the administration of granulocyte-colony stimulating factor (G-CSF). A bone marrow examination showed moderate hyper-cellularity of granulocytic cells without dysplasia or maturation arrest. Analysis of neutrophil function in vitro demonstrated normal phagocytosis and microbicidal activity, but signiŽ cantly impaired chemotaxis. A test for total haemolytic complement activity (CH50) showed a nondetectable level. All components of the classical pathway were normal except for C6, which was nondetectable. Other family members were healthy with normal white blood cell and neutrophil counts, and normal levels of CH50. Subsequently, the boy complained of frequent simultaneous episodes of high fever, abdominal cramps and diarrhoea from the age of 4 11/12 y. The  at abdomen was soft without tenderness. Repeated stool examinations for culture were negative. The C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were 7 to 10 mg/dl and 40 to 55 mm/h, respectively. Antibiotics, anti-fungal agents and G-CSF were not effective. Colonoscopy at the age of 6 y showed surrounding ulceration in the cecum and a few small ulcers from the ascending and transverse colon. Microscopic examination of biopsy material showed marked inŽ ltration of neutrophils and lymphocytes with granulation tissue. Treatment with prednisolone (1 mg/kg/d) was followed by rapid relief from all symptoms and a remarkable fall in CRP and ESR levels. A colonoscopy 5 mo after the start of prednisolone showed a considerable improvement in the patient’s condition, which then remained stable on a low dose of prednisolone. C6 deŽ ciency is occasionally associated with rheumatic diseases such as systemic lupus erythematosus (SLE) (3), Sjgren syndrome (3), glomerulonephritis (4) and arthritis (5). The mechanism is unclear, but an inability to eliminate weak pathogens that generate immune complexes by their antigens may be considered. However, the association of C6 deŽ ciency with colitis has not been described previously. In several reports the association of colitis with neutropenia and/or neutrophil dysfunction has been described. The association of Crohn’s disease with chronic (6), autoimmune (7) and cyclic types (8) of neutropenia has also been reported. In a collaborative European Study it was found that 77% of patients with glycogen storage disease type Ib have evidence of in ammatory bowel disease (IBD), and that all of them had neutropenia (neutrophil count 500/l), but IBD was not found in the patients without neutropenia (9). So far, there has been no record of the relationship between C6 deŽ ciency and congenital chronic neutropenia and with later manifestation of colitis. Although the occurrence of the two disorders may be coincidental, the possibility that the immunological abnormality is of importance for the development of colitis has to be considered.