Hepatic fungal infection in a young beagle with unrecognised hereditary cobalamin deficiency (Imerslund-Gräsbeck syndrome).

A 12-month-old beagle presented for anorexia, pyrexia and vomiting. The dog had been treated intermittently with antibiotics and corticosteroids for inappetence and lethargy since five months of age. Previous laboratory abnormalities included macrocytosis and neutropenia. At presentation, the dog was lethargic, febrile and thin. Laboratory examination findings included anaemia, a left shift, thrombocytopenia, hypoglycaemia and hyperbilirubinaemia. Multiple, small, hypoechoic, round hepatic lesions were observed on abdominal ultrasound. Cytological examination of hepatic fine needle aspirates revealed a fungal infection and associated pyogranulomatous inflammation. The dog's general condition deteriorated despite supportive measures and treatment with fluconazole, and owners opted for euthanasia before hypocobalaminaemia was identified. Subsequent genomic analysis revealed a CUBN:c.786delC mutation in a homozygous state, confirming hereditary cobalamin malabsorption (Imerslund-Gräsbeck syndrome). Similar to human infants, dogs with Imerslund-Gräsbeck syndrome may rarely be presented for infectious diseases, distracting focus from the underlying primary disorder.

The role of Helicobacter pylori infection in hematological disorders.

Helicobacter pylori (H. pylori) is a Gram-negative spiral bacterium, classified as a carcinogen of class I, according to the World Health Organization (WHO). The infection is a major cause of gastritis, gastric and duodenal ulcer disease and increases the risk of gastric cancer. It has been implicated in the pathogenesis of several gastrointestinal, systemic or hematological diseases. The present review aims in deciphering the role of the bacterium in hematological disorders, increasing the awareness of gastroenterologists, hematologists and internal medicine practitioners, regarding the bacterium-associated hematological diseases. The efficacy of H. pylori eradication in increasing the platelet count in adult patients with primary immune thrombocytopenia (ITP) has been confirmed, linking the infection with the disease. Moreover, as the bacterium causes iron deficiency anemia (IDA) by several mechanisms, recent guidelines indicate H. pylori infection (Hp-I) to be sought in IDA patients if histology is negative and to be eradicated if present. Furthermore, it has been widely recognized that anti-H. pylori treatment causes regression of the low-grade B-cell gastric MALT lymphomas. Despite the well established associations of Hp-I with the aforementioned hematological disorders, we highlight the possible role of the infection to other hematological diseases or conditions such as non-Hodgkin lymphomas of the stomach, monoclonal gammopathy of undetermined significance, megaloblastic anemia and myelodysplastic syndromes. We finally underline the elevated risk of childhood leukemia and of hemorrhage in patients with coagulation disorders, due to the infection.

[Megaloblastic anemia associated with chronic diarrhea. A prospective and multicenter study in Lima]. / Anemia megaloblástica asociada a diarrea crónica. Estudio prospectivo y multicéntrico en Lima.

Since 1986 we have been observing an increased number of patients with megaloblastic anaemia (MA) associated to chronic diarrhea. In 60% of the cases we could not identify any etiologic factor. In the last three years a prospective study in Lima (Peru) has been carried on aimed to investigate this aspect; patients with diseases recognized to be associated to MA were excluded. 45 patients were included age average 37.5 years, all of them have a confirmed diagnosis by bone marrow; 64% with low serum B12 and folic acid, 20% with low serum B12, and 16% with low serum folic acid. Gastric biopsies did not show atrophy in 67%; intragastric pH was lower than 4 in 50% duodenal content culture was positive in 35% (6/17) to aerobic gram negative agents; 62% (5/8) of duodenal biopsies, 83% (5/6) of jejunal biopsies, 4/4 (100%) of ileal biopsies, showed diverse structural changes; 100% did not show Diphyllobothrium pacificum. All these findings make us suggest that a significative number of patients with MA and chronic diarrhea in Lima are related to small bowel bacterial overgrowth. These bacteria can "sequestrate" or consume folates and cobalamines besides the direct damage they can cause to intestinal morphology. Future studies are needed to confirm our proposal and define if these cases belong to a variety of tropical sprue.

Production of vitamin B 12 analogues in patients with small-bowel bacterial overgrowth.

We investigated the presence of vitamin B 12 analogues (cobamides) and the bacterial conversion of 57Co-B12 (vitamin B12 cyanocobalamin, [57Co]-CN-Cbl) into cobamides in the intestinal contents of four patients with bacterial overgrowth. The (57Co)-CN-Cbl bound to intrinsic factor was given orally. Jejunal contents were aspirated for 24 h and cultured aerobically and anaerobically. The CN-Cbl and cobamides were separated by electrophoresis and chromatography and identified by bioautography. Radioactivity of cobamide zones from duplicate chromatograms showed bacterial conversion of (57Co)-cn-cbl into cobamides. Cobamides ([Ade]CNCBA, [2-Me Ade] CNCba, [CN]2Cbi and factor E) were found in the intestinal contents in three of the four patients, and in two of three patients cobamides represented more than 25% of the administered CN-Cbl. Thus bacterial production of cobamides, both de novo and from ingested CN-Cbl bound to intrinsic factor, occurs in humans with bacterial overgrowth states and results in a significant loss of vitamin B12 to the host.