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Abnormal blood folate concentration

MedGen UID:
866690
Concept ID:
C4021037
Finding
Synonyms: Abnormal serum folate; Abnormality of folate in blood
 
HPO: HP:0040087

Definition

Any deviation from the normal concentration of folate in the blood circulation. [from HPO]

Conditions with this feature

Transcobalamin II deficiency
MedGen UID:
137976
Concept ID:
C0342701
Disease or Syndrome
Transcobalamin II deficiency (TCN2D) is an autosomal recessive disorder with onset in early infancy characterized by failure to thrive, megaloblastic anemia, and pancytopenia. Other features include methylmalonic aciduria, recurrent infections, and vomiting and diarrhea. Treatment with cobalamin results in clinical improvement, but the untreated disorder may result in mental retardation and neurologic abnormalities (summary by Haberle et al., 2009). Hall (1981) gave a clinically oriented review of congenital defects of vitamin B12 transport, and Frater-Schroder (1983) gave a genetically oriented review.
Methylcobalamin deficiency type cblG
MedGen UID:
344426
Concept ID:
C1855128
Disease or Syndrome
Disorders of intracellular cobalamin metabolism have a variable phenotype and age of onset that are influenced by the severity and location within the pathway of the defect. The prototype and best understood phenotype is cblC; it is also the most common of these disorders. The age of initial presentation of cblC spans a wide range: In utero with fetal presentation of nonimmune hydrops, cardiomyopathy, and intrauterine growth restriction. Newborns, who can have microcephaly, poor feeding, and encephalopathy. Infants, who can have poor feeding and slow growth, neurologic abnormality, and, rarely, hemolytic uremic syndrome (HUS). Toddlers, who can have poor growth, progressive microcephaly, cytopenias (including megaloblastic anemia), global developmental delay, encephalopathy, and neurologic signs such as hypotonia and seizures. Adolescents and adults, who can have neuropsychiatric symptoms, progressive cognitive decline, thromboembolic complications, and/or subacute combined degeneration of the spinal cord.
Constitutional megaloblastic anemia with severe neurologic disease
MedGen UID:
462555
Concept ID:
C3151205
Disease or Syndrome
Dihydrofolate reductase deficiency is an autosomal recessive metabolic disorder characterized by the hematologic findings of megaloblastic anemia and variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy (Banka et al., 2011) to childhood absence epilepsy with learning difficulties to lack of symptoms (Cario et al., 2011). Treatment with folinic acid can ameliorate some of the symptoms.
Imerslund-Grasbeck syndrome type 1
MedGen UID:
865256
Concept ID:
C4016819
Finding
3-Methylglutaconic aciduria type I (MGCA1) is a rare autosomal recessive disorder of leucine catabolism. The metabolic landmark is urinary excretion of 3-methylglutaconic acid (3-MGA) and its derivatives 3-methylglutaric acid (3-MG) and 3-hydroxyisovaleric acid (3-HIVA). Two main presentations have been described: one with onset in childhood associated with the nonspecific finding of psychomotor retardation, and the other with onset in adulthood of a progressive neurodegenerative disorder characterized by ataxia, spasticity, and sometimes dementia; these patients develop white matter lesions in the brain. However, some asymptomatic pediatric patients have been identified by newborn screening and show no developmental abnormalities when reexamined later in childhood (summary by Wortmann et al., 2010). Genetic Heterogeneity and Classification of Methylglutaconic Aciduria Methylglutaconic aciduria is a clinically and genetically heterogeneous disorder. Type II MGCA (MGCA2), also known as Barth syndrome (BTHS; 302060), is caused by mutation in the tafazzin gene (TAZ; 300394) on chromosome Xq28. It is characterized by mitochondrial cardiomyopathy, short stature, skeletal myopathy, and recurrent infections; cognitive development is normal. Type III MGCA (MGCA3; 258501), caused by mutation in the OPA3 gene (606580) on chromosome 19q13, involves optic atrophy, movement disorder, and spastic paraplegia. In types II and III, the elevations of 3-methylglutaconate and 3-methylglutarate in urine are modest. Type IV MGCA (MGCA4; 250951) represents an unclassified group of patients who have severe psychomotor retardation and cerebellar dysgenesis. Type V MGCA (MGCA5; 610198), caused by mutation in the DNAJC19 gene (608977) on chromosome 3q26, is characterized by early-onset dilated cardiomyopathy with conduction defects, nonprogressive cerebellar ataxia, testicular dysgenesis, and growth failure in addition to 3-methylglutaconic aciduria (Chitayat et al., 1992; Davey et al., 2006). Type VI MGCA (MGCA6; 614739), caused by mutation in the SERAC1 gene (614725) on chromosome 6q25, includes deafness, encephalopathy, and a Leigh-like syndrome. Type VII MGCA (MGCA7B, 616271 and MGCA7A, 619835), caused by mutation in the CLPB gene (616254) on chromosome 11q13, includes cataracts, neurologic involvement, and neutropenia. Type VIII MGCA (MGCA8; 617248) is caused by mutation in the HTRA2 gene (606441) on chromosome 2p13. Type IX MGCA (MGCA9; 617698) is caused by mutation in the TIMM50 gene (607381) on chromosome 19q13. Eriguchi et al. (2006) noted that type I MGCA is very rare, with only 13 patients reported in the literature as of 2003. Wortmann et al. (2013) proposed a pathomechanism-based classification for 'inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature.'
Immunodeficiency 114, folate-responsive
MedGen UID:
1848890
Concept ID:
C5882719
Disease or Syndrome
Folate-responsive immunodeficiency-114 (IMD114) is an autosomal recessive immunologic disorder characterized by the onset of oral ulcers and recurrent skin and respiratory infections in early infancy. Affected individuals have lip fissures, skin sores and abscesses, genital dermatitis, chronic diarrhea, and poor overall growth. Laboratory studies show megaloblastic anemia, thrombocytopenia, and lymphopenia with decreased Ig levels. Some individuals have global developmental delay, often with brain imaging abnormalities. Treatment with folic acid supplementation results in significant clinical improvement of the hematologic and immunologic abnormalities, although neurologic abnormalities, if already present, do not respond to treatment. Early intervention and treatment with folic acid supplementation may prevent or delay neurologic deficits in affected infants (Gok et al., 2023; Shiraishi et al., 2023).

Professional guidelines

PubMed

Reilly R, McNulty H, Pentieva K, Strain JJ, Ward M
Proc Nutr Soc 2014 Feb;73(1):47-56. Epub 2013 Oct 17 doi: 10.1017/S0029665113003613. PMID: 24131523
Tettenborn B
CNS Drugs 2006;20(5):373-87. doi: 10.2165/00023210-200620050-00003. PMID: 16696578
Sarkar PK, Lambert LA
Int J Clin Pract 2001 May;55(4):262-8. PMID: 11406912

Recent clinical studies

Etiology

Crider K, Williams J, Qi YP, Gutman J, Yeung L, Mai C, Finkelstain J, Mehta S, Pons-Duran C, Menéndez C, Moraleda C, Rogers L, Daniels K, Green P
Cochrane Database Syst Rev 2022 Feb 1;2(2022) doi: 10.1002/14651858.CD014217. PMID: 36321557Free PMC Article
Chen H, Zhang Y, Wang D, Chen X, Li M, Huang X, Jiang Y, Dou Y, Wang Y, Ma X, Sheng W, Jia B, Yan W, Huang G; SPCC (Shanghai Preconception Cohort) Group
Ann Intern Med 2022 Sep;175(9):1212-1220. Epub 2022 Aug 23 doi: 10.7326/M22-0741. PMID: 35994746
Obeid R, Oexle K, Rißmann A, Pietrzik K, Koletzko B
J Perinat Med 2016 Apr;44(3):261-8. doi: 10.1515/jpm-2014-0346. PMID: 25825915
Langman LJ, Cole DE
Crit Rev Clin Lab Sci 1999 Aug;36(4):365-406. doi: 10.1080/10408369991239231. PMID: 10486705
Bailey LB
J Nutr 1990 Nov;120 Suppl 11:1508-11. doi: 10.1093/jn/120.suppl_11.1508. PMID: 2243297

Diagnosis

Crider K, Williams J, Qi YP, Gutman J, Yeung L, Mai C, Finkelstain J, Mehta S, Pons-Duran C, Menéndez C, Moraleda C, Rogers L, Daniels K, Green P
Cochrane Database Syst Rev 2022 Feb 1;2(2022) doi: 10.1002/14651858.CD014217. PMID: 36321557Free PMC Article
Sahin-Uysal N, Gulumser C, Kocaman E, Varan B, Bayraktar N, Yanık F
J Matern Fetal Neonatal Med 2020 Aug;33(15):2649-2656. Epub 2019 Jul 1 doi: 10.1080/14767058.2019.1633300. PMID: 31256695
Obeid R, Oexle K, Rißmann A, Pietrzik K, Koletzko B
J Perinat Med 2016 Apr;44(3):261-8. doi: 10.1515/jpm-2014-0346. PMID: 25825915
Tsang BL, Devine OJ, Cordero AM, Marchetta CM, Mulinare J, Mersereau P, Guo J, Qi YP, Berry RJ, Rosenthal J, Crider KS, Hamner HC
Am J Clin Nutr 2015 Jun;101(6):1286-94. Epub 2015 Mar 18 doi: 10.3945/ajcn.114.099994. PMID: 25788000
Savage D, Lindenbaum J
Medicine (Baltimore) 1986 Sep;65(5):322-38. doi: 10.1097/00005792-198609000-00005. PMID: 3747828

Therapy

Crider K, Williams J, Qi YP, Gutman J, Yeung L, Mai C, Finkelstain J, Mehta S, Pons-Duran C, Menéndez C, Moraleda C, Rogers L, Daniels K, Green P
Cochrane Database Syst Rev 2022 Feb 1;2(2022) doi: 10.1002/14651858.CD014217. PMID: 36321557Free PMC Article
Crider KS, Qi YP, Yeung LF, Mai CT, Head Zauche L, Wang A, Daniels K, Williams JL
Annu Rev Nutr 2022 Aug 22;42:423-452. doi: 10.1146/annurev-nutr-043020-091647. PMID: 35995050Free PMC Article
Chen H, Zhang Y, Wang D, Chen X, Li M, Huang X, Jiang Y, Dou Y, Wang Y, Ma X, Sheng W, Jia B, Yan W, Huang G; SPCC (Shanghai Preconception Cohort) Group
Ann Intern Med 2022 Sep;175(9):1212-1220. Epub 2022 Aug 23 doi: 10.7326/M22-0741. PMID: 35994746
Obeid R, Oexle K, Rißmann A, Pietrzik K, Koletzko B
J Perinat Med 2016 Apr;44(3):261-8. doi: 10.1515/jpm-2014-0346. PMID: 25825915
Bailey LB
J Nutr 1990 Nov;120 Suppl 11:1508-11. doi: 10.1093/jn/120.suppl_11.1508. PMID: 2243297

Prognosis

Crider K, Williams J, Qi YP, Gutman J, Yeung L, Mai C, Finkelstain J, Mehta S, Pons-Duran C, Menéndez C, Moraleda C, Rogers L, Daniels K, Green P
Cochrane Database Syst Rev 2022 Feb 1;2(2022) doi: 10.1002/14651858.CD014217. PMID: 36321557Free PMC Article
van Uitert EM, Steegers-Theunissen RP
Mol Nutr Food Res 2013 Apr;57(4):582-95. Epub 2012 Dec 4 doi: 10.1002/mnfr.201200084. PMID: 23213022
Obeid R, Herrmann W
Curr Drug Metab 2012 Oct;13(8):1184-95. doi: 10.2174/138920012802850137. PMID: 22746304
Snodgrass SR
Mol Neurobiol 1992 Spring;6(1):41-73. doi: 10.1007/BF02935566. PMID: 1463588
Savage D, Lindenbaum J
Medicine (Baltimore) 1986 Sep;65(5):322-38. doi: 10.1097/00005792-198609000-00005. PMID: 3747828

Clinical prediction guides

Crider K, Williams J, Qi YP, Gutman J, Yeung L, Mai C, Finkelstain J, Mehta S, Pons-Duran C, Menéndez C, Moraleda C, Rogers L, Daniels K, Green P
Cochrane Database Syst Rev 2022 Feb 1;2(2022) doi: 10.1002/14651858.CD014217. PMID: 36321557Free PMC Article
Singh CK, Kumar A, Lavoie HA, Dipette DJ, Singh US
Exp Biol Med (Maywood) 2013 May;238(5):482-90. Epub 2013 May 29 doi: 10.1177/1535370212473704. PMID: 23436883Free PMC Article
van Uitert EM, Steegers-Theunissen RP
Mol Nutr Food Res 2013 Apr;57(4):582-95. Epub 2012 Dec 4 doi: 10.1002/mnfr.201200084. PMID: 23213022
Snodgrass SR
Mol Neurobiol 1992 Spring;6(1):41-73. doi: 10.1007/BF02935566. PMID: 1463588
Savage D, Lindenbaum J
Medicine (Baltimore) 1986 Sep;65(5):322-38. doi: 10.1097/00005792-198609000-00005. PMID: 3747828

Recent systematic reviews

Crider K, Williams J, Qi YP, Gutman J, Yeung L, Mai C, Finkelstain J, Mehta S, Pons-Duran C, Menéndez C, Moraleda C, Rogers L, Daniels K, Green P
Cochrane Database Syst Rev 2022 Feb 1;2(2022) doi: 10.1002/14651858.CD014217. PMID: 36321557Free PMC Article
Oussalah A, Levy J, Filhine-Trésarrieu P, Namour F, Guéant JL
Am J Clin Nutr 2017 Oct;106(4):1142-1156. Epub 2017 Aug 16 doi: 10.3945/ajcn.117.156349. PMID: 28814397Free PMC Article
Shere M, Bapat P, Nickel C, Kapur B, Koren G
J Obstet Gynaecol Can 2015 Jun;37(6):527-33. doi: 10.1016/s1701-2163(15)30229-2. PMID: 26334605
Marchetta CM, Devine OJ, Crider KS, Tsang BL, Cordero AM, Qi YP, Guo J, Berry RJ, Rosenthal J, Mulinare J, Mersereau P, Hamner HC
Nutrients 2015 Apr 10;7(4):2663-86. doi: 10.3390/nu7042663. PMID: 25867949Free PMC Article
Tsang BL, Devine OJ, Cordero AM, Marchetta CM, Mulinare J, Mersereau P, Guo J, Qi YP, Berry RJ, Rosenthal J, Crider KS, Hamner HC
Am J Clin Nutr 2015 Jun;101(6):1286-94. Epub 2015 Mar 18 doi: 10.3945/ajcn.114.099994. PMID: 25788000

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