Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.7.1 (methylenetetrahydrofolate reductase)
 2,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review highlights the features of cobalamin and folate deficiency and insufficiency that are particular to children. Maternal deficiency of cobalamin and insufficiency or deficiency of folate are the principal causes of deficiencies of these vitamins in the newborn. Maternal cobalamin deficiency can be caused by pernicious anemia or postgastrectomy, but most often results from a diet lacking in animal protein. The mothers are usually not anemic and failure to thrive and neurological deficits are more common in their infants than is megaloblastic anemia. Inborn errors of cobalamin transport and metabolism present with homocystinuria and methylmalonic aciduria, either alone or in combination. They share many of the clinical features of nutritional cobalamin deficiency. Maternal folate insufficiency results in neural tube defects, fetal loss, prematurity, and fetal growth retardation. Inborn errors of folate metabolism are rare, but polymorphisms affecting the gene for methylenetetrahydrofolate reductase (MTHFR) are common and may have significant health implications. Elevation of plasma methylmalonic acid (MMA) levels reflects a functional lack of cobalamin, whereas elevated total homocysteine levels are associated with a lack of either folate or cobalamin. The determination of these should be part of the investigation of failure to thrive, neurological disorders, and unexplained anemia or cytopenias in children.
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PMID:Cobalamin and folate deficiency: acquired and hereditary disorders in children. 993 May 66

The specific aim of the current study of 133 women with at least 1 pregnancy and measures of hypofibrinolytic and thrombophilic gene mutations was to determine retrospectively whether the mutations were associated with adverse pregnancy outcomes including prematurity, miscarriage, stillbirth, intrauterine growth retardation (IUGR), eclampsia, and abruptio placentae. Four gene mutations (factor V Leiden, methylenetetrahydrofolate reductase [MTHFR], prothrombin, and 4G/5G polymorphism of the plasminogen activator inhibitor type 1 [PAI-1] gene) were assessed by polymerase chain reaction (PCR). One hundred twenty-two women were genotyped for all 4 genes and divided into gene mutation (n = 68) and non-gene (n = 54) groups. The gene mutation group included those with at least 1 thrombophilic mutation (heterozygous for factor V Leiden, heterozygous for prothrombin, and homozygous for MTHFR), or hypofibrinolysis with homozygosity for the 4G polymorphism of the PAI-1 gene. The non-gene mutation group included those with no mutation for all 4 genes (wild-type normal) or who were wild-type normal for the prothrombin and factor V Leiden mutations and heterozygous for MTHFR and/or 4G/5G for the PAI-1 gene, neither heterozygosity associated with coagulation abnormalities. The 68 women with gene mutations, versus 54 in the non-gene mutation group, has more prematurity (10% v 4%, chi2 = 5.4, P = .021), more IUGR (3% v 0%, P = .035), and more total complications of pregnancy (37% v 21%, chi2 = 11.6, P = .001). The number of pregnancies (P = .0001) and 4G/4G polymorphism of the PAI-1 gene (P = .029) were positively associated with complications of pregnancy by stepwise logistic regression when the age, number of pregnancies, and all 4 gene mutations were the explanatory variables. Heritable hypofibrinolysis, mediated by 4G/4G homozygosity for the PAI-1 gene, is an independent significant, potentially reversible risk factor for pregnancy complications, probably acting through thrombotic induction of placental insufficiency.
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PMID:The 4G/4G polymorphism of the hypofibrinolytic plasminogen activator inhibitor type 1 gene: an independent risk factor for serious pregnancy complications. 1090 93

Diamond-Blackfan anemia is a congenital hypoproliferative anemia known to be associated with diverse physical anomalies affecting the thumb, craniofacial bones, urogenital system, and heart; prematurity; and fetal demise. We report the case of a 16-month-old boy with Diamond-Blackfan anemia noted to have decreased use of his right side since birth. Magnetic resonance imaging demonstrated a large area of encephalomalacia in the left middle cerebral artery territory. Magnetic resonance angiography showed marked attenuation of the left middle cerebral artery, suggesting a remote thromboembolic event. The laboratory results were remarkable for a decreased hemogolobin of 9.5 g/dL and increased platelets of 591,000/microL. He was heterozygous for the methylenetetrahydrofolate reductase gene C677T mutation. An echocardiogram demonstrated a patent foramen ovale versus an atrial septal defect with left to right shunting. Perinatal stroke may be a rare complication of Diamond-Blackfan anemia in the setting of other risk factors.
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PMID:A child with Diamond-Blackfan anemia, methylenetetrahydrofolate reductase mutation, and perinatal stroke. 1469 10