Congenital neutropenia: diagnosis, molecular bases and patient management

The term congenital neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, severe (<0.5 G/l) or mild (between 0.5-1.5 G/l), which may also affect other organ systems such as the pancreas, central nervous system, heart, muscle and skin. Neutropenia can lead to life-threatening pyogenic infections, acute gingivostomatitis and chronic parodontal disease, and each successive infection may leave permanent sequelae. The risk of infection is roughly inversely proportional to the circulating polymorphonuclear neutrophil count and is particularly high at counts below 0.2 G/l. When neutropenia is detected, an attempt should be made to establish the etiology, distinguishing between acquired forms (the most frequent, including post viral neutropenia and auto immune neutropenia) and congenital forms that may either be isolated or part of a complex genetic disease. Except for ethnic neutropenia, which is a frequent but mild congenital form, probably with polygenic inheritance, all other forms of congenital neutropenia are extremely rare and have monogenic inheritance, which may be X-linked or autosomal, recessive or dominant. About half the forms of congenital neutropenia with no extra-hematopoetic manifestations and normal adaptive immunity are due to neutrophil elastase (ELANE) mutations. Some patients have severe permanent neutropenia and frequent infections early in life, while others have mild intermittent neutropenia. Congenital neutropenia may also be associated with a wide range of organ dysfunctions, as for example in Shwachman-Diamond syndrome (associated with pancreatic insufficiency) and glycogen storage disease type Ib (associated with a glycogen storage syndrome). So far, the molecular bases of 12 neutropenic disorders have been identified. Treatment of severe chronic neutropenia should focus on prevention of infections. It includes antimicrobial prophylaxis, generally with trimethoprim-sulfamethoxazole, and also granulocyte-colony-stimulating factor (G-CSF). G-CSF has considerably improved these patients' outlook. It is usually well tolerated, but potential adverse effects include thrombocytopenia, glomerulonephritis, vasculitis and osteoporosis. Long-term treatment with G-CSF, especially at high doses, augments the spontaneous risk of leukemia in patients with congenital neutropenia.     

Campylobacter fetus bacteremia in an immunocompromised patient: case report and review of the literature

A 33-year-old woman underwent a liver transplantation and splenectomy in 1985 and had followed immunosuppressive therapy until 1995. Afterwards a non-Hodgkin lymphoma was diagnosed and chemotherapy was started. In January 2000, because of suspect transplantation rejection she was treated with steroid and immunosuppressive therapy. Fever occurred after two months and Cytomegalovirus (CMV) infection was diagnosed. Ganciclovir was started with clinical remission. In November 2000 fever recurred without clinical symptoms. Lymphoma recurrence was excluded and CMV was detected by PCR in several biological fluids. Blood cultures were positive for a bacterium that was identified as Campylobacter fetus. The patient was successfully treated with intravenous ciprofloxacin. For persistent CMV viremia therapy with gancyclovir was stopped and foscarnet was used (60mg/Kg/tid i.v. for two weeks). Bacteremia due to C. fetus is rare, occurring mainly in immunocompromised patients. In our patient the immunosuppressive therapy, chemotherapy for lymphoma and CMV infection had made the patient susceptible to bacteremia with this infrequently found bacterium. The clinical microbiologist should be aware of this infection in immunocompromised hosts.     

Congenital alacrima in a patient with G (Opitz Frias) syndrome

Congenital alacrima is an autosomal dominant disorder showing markedly deficient lacrimation and punctate corneal epithelial erosions. The G (Opitz-Frias) syndrome is also an autosomal dominant disorder characterised by hypertelorism, hypospadias, stridor, and dysphagia. Here we report a 5-year-old boy with the G syndrome presenting congenital alacrima. Received: 23 August 1995 / Revised: 25 September 1995     

Anaerobic respiration of fumarate as a differential test betweenCampylobacter fetus andCampylobacter jejuni

The effect of formate and of various electron acceptors—fumarate, aspartate, or nitrate—on the growth of 36 catalase-producingCampylobacter strains was quantitatively investigated in a semisynthetic medium, under aerobic (5% oxygen, 10% carbon dioxide, 85% nitrogen) or anaerobic (10% carbon dioxide, 90% nitrogen) conditions. Under anaerobic conditions, 24 strains ofC. jejuni failed to grow, or grew poorly, in the presence of fumarate, whereas ten strains ofC. fetus subsp.fetus and two strains ofC. fetus subsp.venerealis grew abundantly, rather better than under aerobic conditions. The quantitative differences of growth yields were very significant between the two species with fumarate, but less pronounced with aspartate or nitrate. The activity of fumarate-reductase inC. fetus was substantiated by identification of relevant metabolites by gas liquid chromatography and by mass spectrometry. The anaerobic fumarate respiration in the genusCampylobacter has taxonomic implications.