ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing

Hickey, Scott E.; Curry, Cynthia J.; Toriello, Helga V.

doi:10.1038/gim.2012.165

Cited by 131 publications

(102 citation statements)

References 76 publications

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“…Using current procedural terminology of the American Medical Association (CPT) laboratory codes to estimate test cost, the WVUH clinical laboratory billed approximately $120 to perform testing of both MTHFR alleles in each of 1,141 patients, for a CPT conservative cost estimate of $137,000. Our data support the growing consensus that MTHFR testing should not be routinely ordered for thrombophilia testing [USPSTF 2009;Leawood 2012;Hickey, Curry, Toriello 2013], and we intend to bring these data to the attention of the clinicians who order these tests.…”

Section: Resultssupporting

confidence: 75%

Non-Association of Methylenetetrahydrofolate Reductase (MTHFR) Polymorphisms with Homocysteine Levels, Venous or Arterial Thromboses in 1,141 North-Central Appalachian Patients

Khimani

Perrotta

Hobbs

et al. 2016

CCO

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Objectives: MTHFR polymorphism testing has been used by clinicians for thrombophilia risk assessment. We questioned the utility of such testing.Methods: 1,141 patients age 18 and above had MTHFR testing for both C677T and A1298C polymorphisms, 2006 through 2012. Available plasma homocysteine levels were obtained and ICD-9 billing codes were grouped to identify venous or arterial clots in these patients.Results: 901 women and 240 men were tested; median age in women was 33 years (range 18-86); median age in men was 47 years (range 18-83). County of residence mapping confirmed that this MTHFR tested population was from north-central Appalachia. Only 144 (13%) of the 1,141 patients had no polymorphism at either the C677T or the A1298C locus; only 4 patients (0.4%) had 3 or more polymorphisms; 993 patients (87%) had either one or two polymorphisms.We found polymorphism frequency pattern similar in both sexes. Although men had higher homocysteine levels, MTHFR polymorphisms did not associate with homocysteine levels in either sex. In 901 women tested, the ICD-9 coded incidence of arterial clots was 20%, and of venous clots was 21%; in 240 men tested, the incidence of arterial clots was 48% and of venous clots was 40%. MTHFR polymorphisms did not associate with arterial or venous clots in either sex.Based on CPT billing codes, a minimal cost estimate was $137,000 for performing these 1,141 MTHFR tests.Conclusions: MTHFR testing was costly and did not add useful information during thrombophilia evaluation in this patient population.

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Section: Resultssupporting

confidence: 75%

Non-Association of Methylenetetrahydrofolate Reductase (MTHFR) Polymorphisms with Homocysteine Levels, Venous or Arterial Thromboses in 1,141 North-Central Appalachian Patients

Khimani

Perrotta

Hobbs

et al. 2016

CCO

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“…36 The association of MTHFR mutations with stroke and thrombosis not only is inconsistent but has virtually been disproven to the point of new guidelines suggesting testing is no longer warranted. 37 The predominance of this so-called genetic thrombophilia in the literature for so long across so many studies may highlight the complexities of defining such relationships and the high risk of falsepositive associations.…”

Section: Discussionmentioning

confidence: 99%

Thrombophilia risk is not increased in children after perinatal stroke

Curtis

Mineyko

Massicotte

et al. 2017

Blood

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Key Points• Thrombophilia in children with perinatal stroke is rare, with rates similar to those in the normal population.• Routine testing in childhood is not indicated.Perinatal stroke causes cerebral palsy and lifelong disability. Specific diseases are definable, but mechanisms are poorly understood. Evidence suggests possible associations between arterial perinatal stroke and prothrombotic disorders, but population-based, controlled, disease-specific studies are limited. Understanding thrombophilia in perinatal stroke informs pathogenesis models and clinical management.We conducted a population-based, prospective, case-control study to determine the association of specific perinatal stroke diseases with known thrombophilias. Children with idiopathic magnetic resonance imaging-classified neonatal arterial ischemic stroke (NAIS), arterial presumed perinatal ischemic stroke (APPIS), or fetal periventricular venous infarction (PVI) were recruited. Standardized thrombophilia evaluations were performed after 12 months of age on stroke cases and controls, including quantified proteins C and S, antithrombin, factors VIII/IX/XI, fibrinogen, lipoprotein(a), homocysteine, lupus anticoagulant, anticardiolipin antibodies and genotyping of factor V Leiden (FVL), factor II G20210A (FII), and methylenetetrahydrofolate reductase C677T. A total of 212 children were studied: 46 with NAIS, 34 with APPIS, 55 with PVI, and 77 controls (male, 53%; median age, 4.8 years). Of 14 parameters, no differences were observed in 12, including all common thrombophilias. Mean prothrombin time was shorter in arterial strokes (P < .001). Rates of antiphospholipid antibodies were low, comparable to those in controls, and resolved on repeat testing. FVL and FII rates were comparable to population norms. Total number of possible abnormalities did not differ between cases and controls. Our prospective, population-based, controlled, disease-specific study suggests minimal association between perinatal stroke and thrombophilia. This does not exclude the possibility of disordered coagulation at the time of stroke but suggests testing in childhood is not indicated. (Blood. 2017;129(20):2793-2800 Medscape Continuing

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“…MTHFR gene polymorphisms have been linked to a variety of conditions ranging from autism to cancer, from hypertension to recurrent pregnancy loss, as well as peripheral artery disease, migraine, and various neuropsychiatric diseases. 19,20 Folic acid, is a synthetic vitamin which is not found in large amounts in food. Folic acid is stable while the natural forms of folate are unstable.…”

Section: Discussionmentioning

confidence: 99%

Folic Acid; Is Simple Folic Acid Effective to Replenish RBC Folate Stores Among Pakistani Femal Epatients? Small Case.

Yasmin

2017

TPMJ

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ABSTRACT… Objectives: The objective of our study was to assess the effectiveness of folic acid in optimizing the red blood cells folate levels and to observe the frequency of folate resistance among Pakistani female patients. Setting: Outpatient Department of Obstetrics & Gynaecology, Jinnah Post graduate Medical Centre (JPMC), Karachi. Period: January-July 2016. Methodology: Participants fulfilling the inclusion criteria were included after informed consent. Detail history and physical examination was done in each participant. All study participants received 5mg (400 µg) folic acid as a daily supplement for 24 weeks. Red blood cell folate concentrations were measured at baseline and after 24 weeks of therapy. Paired sample t-test was used to find out significant difference between folate levels. Results: A total of 44 women (23 pregnant while 21 non pregnant) were included in the study. Mean age of the participants was 27.6 ± 5.9years and mean BMI was 23.9 ± 4.1kg/m 2 respectively. The mean values of Red blood cells folate at baseline and at 24 weeks were 623.6 ± 406.6 and 861.9 ± 432.4respectively. Paired sample t-test results showed that there was no significant difference. Thirty-two (70.4%) women showed an increase in RBC folate status while 13 (29.6%) women had steady or decreased levels of folate after taking folic acid for 24 weekswhich may be due to RBS enzyme methylenetetrahydrofolate reductase (MTHFR) deficiency. Conclusion: Simple folic acid supplementation is not very helpful in improving folate status in female Pakistani patients. Resistant to improvement may be due to MTHFR deficiency in our study subjects. Key words:Folic

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ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing

Cited by 131 publications

References 76 publications

Non-Association of Methylenetetrahydrofolate Reductase (MTHFR) Polymorphisms with Homocysteine Levels, Venous or Arterial Thromboses in 1,141 North-Central Appalachian Patients

Non-Association of Methylenetetrahydrofolate Reductase (MTHFR) Polymorphisms with Homocysteine Levels, Venous or Arterial Thromboses in 1,141 North-Central Appalachian Patients

Thrombophilia risk is not increased in children after perinatal stroke

Folic Acid; Is Simple Folic Acid Effective to Replenish RBC Folate Stores Among Pakistani Femal Epatients? Small Case.

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