[Apathetic state of mind due to pernicious anemia]. / Apathische gemoedstoestand ten gevolge van een pernicieuze anemie.

In this case study we describe a man who came to a mental health care centre (MHCC) with difficult to interpret complaints such as loss of fear and empathy, apathy and cognitive symptoms. In addition, he experienced a pronounced fatigue. Later he suffered from cold extremities, bilateral hypoesthesia of the hands and paresthesias of the legs. Routine laboratory tests initially showed no abnormalities. Only later a decreased hemoglobin and vitamin B12 value was seen in the context of a pernicious anemia. A treatment with vitamin B12 supplementation was started, after which gradual improvement of the symptoms was seen. This case study shows that vitamin B12 deficiency can result in both psychiatric and cognitive symptoms including memory and attention problems. The initial presentation of pernicious anemia can involve only psychiatric symptoms before neurological and hematological symptoms are present and before anemia is objectively diagnosed.

Nutritional neuropathies.

Neuropathies associated with nutritional deficiencies are routinely encountered by the practicing neurologist. Although these neuropathies assume different patterns, most are length-dependent, sensory axonopathies. Cobalamin deficiency neuropathy is the exception, often presenting with a non-length-dependent sensory neuropathy. Patients with cobalamin and copper deficiency neuropathy characteristically have concomitant myelopathy, whereas vitamin E deficiency is uniquely associated with a spinocerebellar syndrome. In contrast to those nutrients for which deficiencies produce neuropathies, pyridoxine toxicity results in a non-length-dependent sensory neuronopathy. Deficiencies occur in the context of malnutrition, malabsorption, increased nutrient loss (such as with dialysis), autoimmune conditions such as pernicious anemia, and with certain drugs that inhibit nutrient absorption. When promptly identified, therapeutic nutrient supplementation may result in stabilization or improvement of these neuropathies.

[Cancer or vitamin B12 deficiency? Difficult differential diagnosis in elderly]. / Nowotwór czy niedobór witaminy B12? Trudna diagnostyka róznicowa u osób starszych.

Vitamin B12 deficiency anaemia in adults is usually caused by Addison- Biermer's disease. The presence of antibodies against gastric parietal cells and intrinsic factor (IF) in blood is typical for the disease. The gastrointestinal malabsorption or a diet poor in vitamin B12 are rarer causes. The disease manifests in hematological, neurological, psychiatric disorders and trophic changes of the tongue and oral mucosa, which leads to weight loss. A CASE REPORT: The authors describe a case of a 70-year-old woman with severe vitamin B12 deficiency based on chronic inflammatory lesions of the gastric mucosa caused by Helicobacter pylori infection. The patient had haematological (pancytopenia), neurological (problems with memory, concentration, numbness of the limbs, gait instability) and gastrological disorders (loss of appetite, weight loss). The laboratory and imaging diagnostics were performed. The neoplasmatic background was abandoned and pure vitamin B12 deficiency was diagnosed. All symptoms resolved completely after the supplementation and eradication of Helicobacter pylori. CONCLUSIONS: The article demonstrates the problem of many severe, non- specific complications of vitamin B12 deficiency which requires extensive diagnostics and treatment. The similarity of symptoms may suggest a malignant disease especially in elderly patients.

Venous thromboembolism and hyperhomocysteinemia as first manifestation of pernicious anemia: a case series.

BACKGROUND: Hyperhomocysteinemia has been suspected of favoring thrombosis. Several case-control studies and even a meta-analysis have confirmed a link between venous thrombosis and hyperhomocysteinemia. Homocysteine is due to genetic and acquired factors (poor diet in folate and vitamin B12, older age, renal impairment, thyroid diseases, and malignancies) induced by the intake and the concentrations of vitamin B9 or B12 in the majority of cases. CASES PRESENTATION: We report the cases of four Moroccan patients who presented with acute vein thrombosis of different sites: a 34-year-old man, a 60-year-old man, a 58-year-old man, and a 47-year-old woman. All patients had a low level of cobalamin with marked hyperhomocysteinemia with normal serum and red cell folic acid. Venous thrombosis revealed pernicious anemia in all patients. Their low levels of cobalamin, atrophic gastritis, and positive results for gastric parietal cell antibodies confirmed the diagnosis of pernicious anemia. There was no evidence of immobilization, recent surgery, malignancy, antiphospholipid antibody, myeloproliferative disorder, or hormone replacement therapy. No deficiencies in protein C and protein S were detected; they had normal antithrombin III function and factor V Leiden; no prothrombin gene mutations were detected. Treatment included orally administered anticoagulation therapy and cobalamin supplementation. The outcome was favorable in all cases. CONCLUSIONS: These reports demonstrate that pernicious anemia, on its own, can lead to hyperhomocysteinemia that is significant enough to lead to thrombosis. Understanding the molecular pathogenesis of the development of thrombosis in patients with hyperhomocysteinemia related to Biermer disease would help us to identify patients at risk and to treat them accordingly. The literature concerning the relationship between homocysteine and venous thrombosis is briefly reviewed.

Hypersegmented neutrophils and oval macrocytes in the setting of B12 deficiency and pancytopaenia.

Vitamin B12 deficiency is a recognised pathology in several populations, with a particular prevalence in an older adult population. We present two cases whereby vitamin B12 deficiency is the causative factor in marked pancytopaenia. Oval macrocytosis and hypersegmented neutrophils were noted on both peripheral blood samples, which are a characteristic finding in macrocytic anaemia due to B12 deficiency. Distinct underlying pathologies were identified in both cases; food-cobalamin malabsorption and pernicious anaemia. Parenteral vitamin B12 supplementation resulted in a marked reticulocytosis and rapid improvement of haematological indices in both cases. We present this series to serve as a reminder that B12 deficiency can present as life-threatening pancytopaenia.It has has multiple underlying pathologies,defined risk populations and has characteristic blood film findings which can guide investigations, diagnosis and treatment.

COEXISTENCE OF ADDISON'S DISEASE AND PERNICIOUS ANEMIA: IS THE NEW CLASSIFICATION OF AUTOIMMUNE POLYGLANDULAR SYNDROME APPROPRIATE?

A case of autoimmune polyglandular syndrome (APS) is presented. A 45-year-old man was admitted due to fatigue, malaise and inappetence. He had a history of primary hypothyroidism and was on levothyroxine substitution therapy. One year before, he was diagnosed with normocytic anemia and vitamin B12 deficiency, which was treated with vitamin B12 substitution therapy. Physical examination revealed hypotension and marked hyperpigmentation. Laboratory testing showed hyponatremia, hyperkaliemia and severe normocytic anemia. Endocrinological evaluation disclosed low morning cortisol and increased adrenocorticotropic hormone levels. Hence, the diagnosis of Addison's disease was established. Additional laboratory workup showed positive parietal cell antibodies. However, his vitamin B12 levels were increased due to vitamin B12 supplementation therapy, which was initiated earlier. Gastroscopy and histopathology of gastric mucosa confirmed atrophic gastritis. Based on prior low serum vitamin B12 levels, positive parietal cell antibodies and atrophic gastritis, the patient was diagnosed with pernicious anemia. Hydrocortisone supplementation therapy was administered and titrated according to urinary-free cortisol levels. Electrolyte disbalance and red blood cell count were normalized. This case report demonstrates rather unique features of pernicious anemia in a patient with Addison's disease. It also highlights the link between type II and type III APS. Not only do they share the same etiological factors, but also overlap in pathophysiological and clinical characteristics. This case report favors older classification of APS, which consolidates all endocrine and other organ-specific autoimmune diseases into one category. This is important since it might help avoid pitfalls in the diagnosis and treatment of patients with APS.

Advances in mechanisms, diagnosis, and treatment of pernicious anemia.

Pernicious anemia (PA) is an entity initially described in 1849 as a condition that consisted of pallor, weakness, and progressive health decline. Since then several advances led to the conclusion that PA is an autoimmune disease characterized by the deficient absorption of dietary cobalamin. It is currently recognized as the most common cause of cobalamin deficiency worldwide. We hereby review the current understanding of the disease and its neurological, hematological, and biochemical manifestations with emphasis on the diagnostic approach, treatment, and monitoring strategies. We propose an algorithm for the diagnostic approach considering the current performance and limitations of the available diagnostic tools for evaluation of cobalamin status and the presence of autoimmune chronic atrophic gastritis (CAG). Patients with PA require lifelong treatment with cobalamin replacement therapy. The current widely available treatment can be provided through enteral or parenteral cobalamin supplements, with comparable efficacy and tolerability.

Patient journeys: diagnosis and treatment of pernicious anaemia.

BACKGROUND: Instigating a patient support group for patients with pernicious anaemia (PA) revealed dissatisfaction with its current diagnosis and treatment. The authors investigated the clinical features, patient experience of diagnosis and treatment of PA in the UK. METHODS: A total of 889 patients registered with the PA Society support group completed an online survey or postal questionnaire. Outcome measures included clinical features, length of time to diagnosis and patient satisfaction with current treatment RESULTS: One-third of patients experienced symptoms for up to 1 year before diagnosis; 14% waited more than 10 years for a diagnosis. Neurological features were highly prevalent, the most common being memory loss and poor concentration. Nearly two-thirds of respondents were dissatisfied with current treatment; 10% used a non-licensed form of B12 to supplement their prescribed injections. CONCLUSION: The diagnosis and treatment of PA should be subject to a thorough review. This article discusses the patient survey and results and makes recommendations for how the diagnosis and treatment of PA may be evaluated.

Anaemia in pregnancy.

Anaemia in pregnancy, defined as a haemoglobin concentration (Hb) < 110 g/L, affects more than 56 million women globally, two thirds of them being from Asia. Multiple factors lead to anaemia in pregnancy, nutritional iron deficiency anaemia (IDA) being the commonest. Underlying inflammatory conditions, physiological haemodilution and several factors affecting Hb and iron status in pregnancy lead to difficulties in establishing a definitive diagnosis. IDA is associated with increased maternal and perinatal morbidity and mortality, and long-term adverse effects in the new born. Strategies to prevent anaemia in pregnancy and its adverse effects include treatment of underlying conditions, iron and folate supplementation given weekly for all menstruating women including adolescents and daily for women during pregnancy and the post partum period, and delayed clamping of the umbilical cord at delivery. Oral iron is preferable to intravenous therapy for treatment of IDA. B12 and folate deficiencies in pregnancy are rare and may be due to inadequate dietary intake with the latter being more common. These vitamins play an important role in embryo genesis and hence any relative deficiencies may result in congenital abnormalities. Finding the underlying cause are crucial to the management of these deficiencies. Haemolytic anaemias rare also rare in pregnancy, but may have life-threatening complications if the diagnosis is not made in good time and acted upon appropriately.

[Recurrent ischemic stroke revealing Biermer's disease]. / Infarctus cérébral récidivant révélant une maladie de Biermer.

INTRODUCTION: Biermer's disease is an autoimmune disorder characterized by vitamin B12 deficiency. Ischemic stroke is an uncommon complication of Biermer's disease, possibly though hyperhomocysteinemia. CASE REPORT: A 58-year-old male presented with recurrent ischemic stroke. Extensive investigations were normal, except for a high plasma level of homocysteine in the context of pernicious anemia which was otherwise asymptomatic. DISCUSSION: Hyperhomocysteinemia is a known marker, and probably a risk factor, for stroke, fostering atherosclerosis and thrombosis. It can be found among individuals suffering from homocysteinuria, but also when there is deficiency of vitamin B12 or folic acid. Vitamin B12 supplementation would reduce homocysteine concentration which in turn would reduce the risk of ischemic stroke.

Pernicious anemia.

Pernicious anemia is severe anemia most often affecting older adults, caused by failure of the stomach to absorb vitamin B12 and characterized by abnormally large red blood cells, gastrointestinal disturbances, and lesions of the spinal cord. Pernicious anemia is caused by a lack of intrinsic factor and could be an autoimmune disorder. The identification of various autoantibodies helps in the confirmation of the diagnosis and hence towards the patient management. In such patients, oral supplements or intramuscular injections of vitamin B12 are indicated.

Two newborns with nutritional vitamin B12 deficiency: challenges in newborn screening for vitamin B12 deficiency.

Vitamin B12 deficiency causes decreased Methionine Synthase and L-Methylmalonyl-CoA Mutase activity and results in accumulation of Homocysteine, Methylmalonic acid and Propionylcarnitine. Propionylcarnitine is included in tandem mass spectrometry-based newborn screening programs for detection of certain inborn errors of metabolism. We report two asymptomatic newborns with Vitamin B12 deficiency due to maternal deficiencies. One was detected incidentally at 3 weeks of age; the second on supplemental newborn screening based on elevated Propionylcarnitine at 2 days of age. This illustrates the potential for false negative results for Vitamin B12 deficiency screening by acylcarnitine profiling in newborn screening. Homocysteine and Methylmalonic acid may be better markers of Vitamin B12 deficiency. In conclusion, we suggest measuring Methylmalonic acid, Propionylcarnitine and Homocysteine levels in blood spots in expanded newborn screening in order to detect asymptomatic newborns with Vitamin B12 deficiency. Further studies are needed to establish the sensitivity of these three markers in screening for Vitamin B12 deficiency.

[Vitamin B(12) deficiency anaemia in a 7.5 months old girl]. / Niedokrwistosc z niedoboru witaminy B(12) u 7.5-miesiecznej dziewczynki.

Vitamin B(12) stores at birth are adequate for infants until the end of the first year of life even if it 's concentration in maternal breast milk is low. However, there are some situations in which infants have depleted vitamin B(12) stores and in addition have a low dietary intake of cobalamin. Vitamin B(12) depletion occurs in infants who are exclusively breastfed by mothers who have unrecognized pernicious anemia or are strict vegetarians for many years. In those infants symptoms of bone marrow disfunction and impaired development of the central nervous system appear already in the first months of life. Unrecognized cobalamin deficiency may lead to serious neurologic consequences, and even to the death of the child. The authors present a case of a 7.5 month old girl admitted to the Department of Paediatrics, Haematology, Oncology and Endocrinology. Gdansk Medical University suspected of acute leukaemia. Based on a detailed diagnostic procedure a final diagnosis of vitamin B(12) deficiency anaemia was established. The child was exclusively breast-fed. Results of investigations into the reason for cobalamin deficiency in the patient s organism. Led to the diagnosis of pernicious anaemia in the mother. Such a suspicion had been made during pregnancy, but no continuation of investigations nor appropriate treatment were implemented. After treatment with vitamin B(12) supplements and modification of the diet the patient improved quickly and remarkably. A few months follow-up was enough to observe remarkable improvement of psychomotor development of this child.

Does folic acid harm people with vitamin B12 deficiency?

Oral folic acid given before and during pregnancy can prevent about 75% of fetal neural tube defects. Even in large dose (20 mg daily) folic acid has never been shown to harm normal people, but it has acquired a bad reputation in pernicious anaemia. Before 1930, if untreated patients survived the anaemia, they succumbed to peripheral neuritis, subacute combined degeneration of the spinal cord, and death. The speed of this progression was extremely variable. From 1947 onwards, there were many reports of rapid neurological deterioration during administration of folic acid as sole therapy to people with pernicious anaemia. However, a review of clinical studies published before the introduction of liver and vitamin B12 therapy shows that neurological deterioration was often quite as rapid and severe in untreated patients. Oral folic acid can usually correct or prevent the anaemia of pernicious anaemia. Thus it could mask the underlying disease, and allow the development or progression of neurological deterioration, if diagnosis depended on the presence of anaemic symptoms. This possibility can readily be overcome by adequate education of doctors, so that a macrocytic anaemia is not regarded as a necessary accompanying sign of the neurological disorder. The hypothetical and avoidable side-effects of food fortification with folic acid have to be balanced against the certain benefit of preventing neural tube defects in unplanned pregnancies, and also against the probability that adults may be spared the neuropsychiatric and other ill-effects which result from inadequate dietary folic acid.

Unsuspected pernicious anemia in a patient with sickle cell disease receiving routine folate supplementation.

Although the issue of folate supplementation in sickle cell anemia remains controversial, routine supplementation has become common. The major drawback to indiscriminate folate therapy is the potential of masking findings of vitamin B12 (cobalamin) deficiency. This has been dismissed as a problem in sickle cell anemia because of the generally young age of the patients. However, because young blacks, especially women, are at higher risk for developing pernicious anemia than whites, sickle cell anemia and pernicious anemia can be expected to coexist occasionally. In this article we describe such a patient and recommend that routine folate supplementation should not be given in sickle cell anemia before determining the vitamin B12 status.