vitamin-b-12 and Thrombotic-Microangiopathies

Classically, deficiencies of vitamin B

Topics: Anemia, Hemolytic; Female; Folic Acid; Folic Acid Deficiency; Humans; Middle Aged; Purpura, Thrombotic Thrombocytopenic; Thrombotic Microangiopathies; Vitamin B 12; Vitamins

Topics: Humans; Thrombotic Microangiopathies; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Topics: Diagnosis, Differential; Folic Acid Deficiency; Humans; Thrombotic Microangiopathies; Vitamin B 12; Vitamin B 12 Deficiency

Cobalamin C (cblC), a vitamin B12 processing protein, plays a crucial role in metabolism for the conversion of homocysteine to methionine and methylmalonyl-CoA to succinyl-CoA. CblC deficiency, an inborn error of cobalamin processing, is a rare cause of atypical hemolytic-uremic syndrome (aHUS) and results in hyperhomocysteinemia and methylmalonic aciduria. Both substances are thought to contribute to thrombotic microangiopathy (TMA) in cblC deficiency patients. However, the roles of homocysteine and methylmalonic acid (MMA) in these patients remain unclear. We want to shed more light on the contributions of homocysteine and MMA levels as contributing factors for thrombotic microangiopathy (TMA)/aHUS by a follow-up of a cblC deficiency patient over 6 years.. A 27-day-old Hispanic female presented with abnormal C3-carnitine on her newborn screen, poor feeding, decreased activity, and oligouria. She was diagnosed with cblC deficiency after laboratory results revealed elevated serum homocysteine, and serum MMA along with genetic testing showing a homozygous pathogenic frameshift variant in MMACHC. The patient developed aHUS and acute kidney injury (AKI), which resolved after appropriate therapy. Over 6 years, she continued to have normal kidney function with no thrombocytopenia despite persistently elevated homocysteine and MMA levels.. We question the roles of homocysteine and MMA as causative of aHUS/TMA in cblC deficiency as they remained elevated during follow-up but did not result in aHUS/TMA or AKI. Hyperhomocysteinemia and/or MMA caused by other metabolic diseases do not result in aHUS/TMA or AKI. This suggests that other nephrotoxic factors may trigger aHUS/TMA in cblC patients.

Topics: Acute Kidney Injury; Amino Acid Metabolism, Inborn Errors; Atypical Hemolytic Uremic Syndrome; Female; Homocysteine; Humans; Hyperhomocysteinemia; Infant, Newborn; Kidney; Methylmalonic Acid; Oxidoreductases; Thrombotic Microangiopathies; Vitamin B 12; Vitamin B 12 Deficiency

Thrombotic microangiopathies (TMAs) are a group of life-threatening conditions requiring urgent management and characterized by a clinical triad of microangiopathic hemolytic anemia, thrombocytopenia, and ischemic tissue injury. Severe vitamin B12 (Cobalamin-Cbl) deficiency or defective cobalamin metabolism, particularly defects in intracellular B12 metabolism, may lead to a TMA-like picture. The latter has been termed metabolism-mediated TMA (MM-TMA). This confusing picture is mediated partly by ineffective erythropoiesis with significant red cell fragmentation resulting in a hemolytic pattern, coupled with reduced platelet production and endothelial injury with organ damage resulting from accumulated toxic byproducts of B12 dysmetabolism. However, unlike in classic thrombotic thrombocytopenic purpura, where therapeutic plasma exchange has to be initiated promptly, cases of MM-TMA can be treated, if diagnosed properly, with adequate B12 replacement.

Topics: Humans; Purpura, Thrombotic Thrombocytopenic; Thrombotic Microangiopathies; Vitamin B 12

Topics: Humans; Thrombotic Microangiopathies; Vitamin B 12; Vitamin B 12 Deficiency

Acquired vitamin B

Topics: Aged; Aged, 80 and over; Anemia, Hemolytic; Female; Humans; Purpura, Thrombotic Thrombocytopenic; Thrombotic Microangiopathies; Vitamin B 12; Vitamin B 12 Deficiency

Pseudo-thrombotic microangiopathy, or Moschcowitz syndrome, is a rare manifestation of vitamin B12 deficiency. It is characterized by microangiopathic hemolytic anemia, reticulocytes, and hematimetric indices that can be normal or that might present a mild megaloblastosis, and which are associated with neurological manifestations. Vitamin B12 can be found in animal-based protein foods. Breastfeeding is an adequate source of this vitamin for children, when maternal serum levels are normal. The case of a 16-month-old infant is presented. She was admitted for hemolytic anemia with transfusion requirement, thrombocytopenia, failure to thrive and developmental delay. During her hospitalization, she was diagnosed with pseudothrombotic microangiopathy caused by vitamin B12 deficiency.. La seudomicroangiopatía trombótica o síndrome de Moschcowitz es una manifestación infrecuente del déficit de vitamina B12. Se caracteriza por anemia hemolítica con características microangiopáticas, reticulocitos e índices hematimétricos normales o con ligera megaloblastosis, asociados a manifestaciones neurológicas. La vitamina B12 está presente en alimentos proteicos de origen animal. La lactancia materna es una fuente adecuada para los niños cuando los niveles maternos son normales. Se presenta a una paciente de 16 meses que se internó por anemia hemolítica con requerimiento transfusional, plaquetopenia, mal progreso pondoestatural y retraso neuromadurativo. Durante su internación se arribó al diagnóstico de seudomicroangiopatía trombótica secundaria a déficit de vitamina B12.

Topics: Anemia, Hemolytic; Female; Humans; Infant; Thrombotic Microangiopathies; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

The pathophysiology of sickle cell disease (SCD) includes vasculopathy as well as anaemia. Elevated plasma homocysteine is a risk factor for vascular disease and may be associated with increased risk of vascular complications in SCD patients. In the present study, microvascular characteristics were assessed in the bulbar conjunctiva of 18 paediatric and 18 adult SCD patients, using the non-invasive technique of computer-assisted intravital microscopy. A vasculopathy severity index (SI) was computed to quantify the degree of microvasculopathy in each patient. Plasma homocysteine and several of its determinants [serum folate and vitamin B12, plasma pyridoxal-5'-phosphate (vitamin B6 status) and creatinine (kidney function)] were measured. Age was strongly correlated with microvasculopathy in the SCD patients, with the SI increasing about 0·1 unit per one-year increase in age (P < 0·001). After adjusting for age, gender, B-vitamin status and creatinine, homocysteine concentration was directly correlated with severity index (P < 0·05). Age and homocysteine concentration were independent predictors of microvasculopathy in SCD patients. It remains to be determined whether lowering homocysteine concentrations using appropriate B-vitamin supplements (folate and vitamins B12 and B6) - particularly if started early in life - could ameliorate microvasculopathy and its associated complications in SCD patients.

Topics: Adolescent; Adult; Anemia, Sickle Cell; Child; Child, Preschool; Creatine; Folic Acid; Homocysteine; Humans; Intravital Microscopy; Microcirculation; Middle Aged; Pyridoxal Phosphate; Severity of Illness Index; Thrombotic Microangiopathies; Vitamin B 12

Topics: Breast Feeding; Humans; Infant; Male; Methylmalonic Acid; Thrombotic Microangiopathies; Vitamin B 12

Topics: Breast Feeding; Humans; Infant; Male; Methylmalonic Acid; Thrombotic Microangiopathies; Vitamin B 12; Vitamin B 12 Deficiency

Microangiopathic haemolytic anaemia with thrombocytopenia, called pseudo-thrombotic microangiopathy (TMA), is a clinically important complication in patients with vitamin B12 deficiency. We herein present a case of an 80-year-old woman with pseudo-TMA after gastrectomy. She was initially suspected with thrombotic thrombocytopenic purpura based on rapid progression of anaemia with schistocytes and thrombocytopenia; however, her anaemia and thrombocytopenia were improved by vitamin B12 supplementation alone, with a single session of plasma exchange. Vitamin B12 deficiency was finally confirmed by low vitamin B12 levels from the patient's initial blood sample. In addition, normal ADAMTS13 activity was proven, lowering the likelihood of thrombotic thrombocytopenic purpura. Therefore, this patient was diagnosed with pseudo-TMA caused by vitamin B12 deficiency. Pseudo-TMA can occur in patients with vitamin B12 deficiency post-gastrectomy.

Topics: ADAMTS13 Protein; Administration, Intravenous; Aged, 80 and over; Anemia, Hemolytic; Asian People; Diagnosis, Differential; Female; Gastrectomy; Humans; Plasmapheresis; Thrombotic Microangiopathies; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B. We report a case of a 46-year-old Moroccan man presenting with severe hemolytic anemia, thrombocytopenia, and renal failure in absence of macrocytosis, thus mimicking a genuine thrombotic thrombocytopenic purpura. Rapid improvement of renal function observed with only hydration and transfusions of packed red blood cells and the presence of pancytopenia suggested a bone marrow deficiency associated to a hemolytic component of unclear origin. Detection of low levels of vitamin B. Diagnosis of pseudothrombotic thrombocytopenic purpura caused by vitamin B

Topics: Acute Kidney Injury; Diagnosis, Differential; Erythrocyte Transfusion; Fluid Therapy; Humans; Kidney Function Tests; Male; Middle Aged; Purpura, Thrombotic Thrombocytopenic; Thrombotic Microangiopathies; Treatment Outcome; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

Inborn errors of cobalamin (Cbl) metabolism form a large group of rare diseases. One of these, Cbl deficiency type C (CblC), is a well-known cause of thrombotic microangiopathy (TMA), especially in infants. However, there has only been a single published case of TMA associated to Cbl deficiency type G (CblG), also known as methionine synthase deficiency (MSD).. A 21-month-old boy presented with pallor and oral ulcers during episodes of upper respiratory infection (URI). Further examination revealed signs of TMA, and the patient progressed to acute renal failure (ARF). Renal biopsy showed TMA. Evaluation for infection and autoantibodies were negative. The C3 and C4 complement fractions were normal. Analysis of the bone marrow aspirate suggested megaloblastic anemia and signs of hematopoiesis activation (secondary to peripheral hemolysis). Although the serum vitamin B12 level was normal, the patient was treated with cyanocobalamin, with no improvement. The ARF and hematologic parameters improved with conservative treatment. A severe relapse occurred during the follow-up, with normal ADAMTS13 activity. The presumed diagnosis was atypical hemolytic uremic syndrome, and the patient was started on eculizumab, but his response was poor, even when the dosage was increased. At this point it was also recognized that his developmental speech was delayed. Based on these findings, whole exome sequencing was performed, leading to the detection of two novel deleterious variants in the gene coding for methionine synthase, confirming the diagnosis of MSD. Subsequent treatment consisted of elevating the patient's serum homocysteine level and starting him on hydroxicobalamin, with normalization of all hematologic parameters although the microalbuminuria remained.. Methionine synthase deficiency is very rare and characterized by megaloblastic anemia and neurological symptoms. We report the second case of MSD associated to TMA previously diagnosed as aHUS in which the patient had a poor response to eculizumab.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Acute Kidney Injury; ADAMTS13 Protein; Anemia, Megaloblastic; Antibodies, Monoclonal, Humanized; Atypical Hemolytic Uremic Syndrome; Biopsy; Bone Marrow; Exome Sequencing; Humans; Hydroxocobalamin; Hyperhomocysteinemia; Infant; Kidney; Language Development Disorders; Male; Metabolism, Inborn Errors; Recurrence; Thrombotic Microangiopathies; Vitamin B 12; Vitamin B Complex

Cobalamin C (CblC) defects are inherited autosomal recessive disorders of vitamin B12 metabolism due to mutations in the MMACHC gene. Renal manifestations include thrombotic microangiopathy (TMA), acute or chronic renal failure, tubulointerstitial nephritis, and proximal renal tubular acidosis. However, reports about glomerular pathologies are scarce.. A 4-year-old boy presented with nephrotic syndrome, arterial hypertension, and chronic anemia but no signs of hemolysis. Renal biopsy showed TMA with ischemic glomerular collapse, foot process effacement, and tubulointerstitial fibrosis. Elevated serum levels of homocysteine suggested a cobalamin C disorder. This was confirmed by the identification of compound heterozygous mutations in the MMACHC gene. Initial therapy consisted of antihypertensive treatment including angiotensin converting enzyme inhibitor (ACEi) leading to blood pressure control and a significant reduction of proteinuria. After a definite diagnosis of CblC deficiency, hydroxocobalamin was introduced. Thereafter, homocysteine levels decreased, anemia resolved, and a further decline of proteinuria with normalization of serum protein levels was noted. Renal function remained stable.. Although uncommon, the clinical picture of CblC defects may be ruled by nephrotic syndrome mimicking glomerulonephritis, minimal change disease, or primary focal and segmental glomerulosclerosis. Key to a correct diagnosis is elevated serum levels of homocysteine, and a definite diagnosis can be confirmed by genetic testing.

Topics: Anemia; Angiotensin-Converting Enzyme Inhibitors; Biopsy; Carrier Proteins; Child, Preschool; Homocysteine; Humans; Hydroxocobalamin; Hypertension, Renal; Kidney; Male; Nephrotic Syndrome; Oxidoreductases; Thrombotic Microangiopathies; Vitamin B 12; Vitamin B 12 Deficiency