U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Congenital defect of folate absorption

MedGen UID:
83348
Concept ID:
C0342705
Disease or Syndrome
Synonym: Hereditary Folate Malabsorption
SNOMED CT: Congenital defect of folate absorption (62578003); Congenital malabsorption of folic acid (62578003); Folic acid transport defect (62578003); Hereditary folate malabsorption (62578003); Folate transport defect (62578003)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): SLC46A1 (17q11.2)
 
Monarch Initiative: MONDO:0009238
OMIM®: 229050
Orphanet: ORPHA90045

Disease characteristics

Excerpted from the GeneReview: Hereditary Folate Malabsorption
Hereditary folate malabsorption (HFM) is characterized by folate deficiency due to impaired intestinal folate absorption and impaired folate transport into the central nervous system. Findings include poor feeding, failure to thrive, and anemia. There can be leukopenia and thrombocytopenia, diarrhea and/or oral mucositis, hypoimmunoglobulinemia, and other immunologic dysfunction resulting in infections, most often Pneumocystis jirovecii pneumonia. Neurologic manifestations include developmental delays, cognitive and motor disorders, behavioral disorders, and seizures. [from GeneReviews]
Authors:
I David Goldman   view full author information

Additional descriptions

From OMIM
Hereditary folate malabsorption is an autosomal recessive disorder characterized by signs and symptoms of folate deficiency that appear within a few months after birth. Infants exhibit low blood and cerebrospinal fluid folate levels with megaloblastic anemia, diarrhea, immune deficiency, infections, and neurologic deficits. Treatment with folate supplementation results in resolution of the signs and symptoms. The disorder is caused by impaired intestinal folate absorption and impaired transport of folate into the central nervous system (summary by Qiu et al., 2006).  http://www.omim.org/entry/229050
From MedlinePlus Genetics
Hereditary folate malabsorption is a disorder that interferes with the body's ability to absorb certain B vitamins (called folates) from food. Folates are important for many cell functions, including the production of DNA and its chemical cousin, RNA.

Infants with hereditary folate malabsorption are born with normal amounts of folates in their body because they obtain these vitamins from their mother's blood before birth. They generally begin to show signs and symptoms of the disorder within the first few months of life because their ability to absorb folates from food is impaired.

Infants with hereditary folate malabsorption experience feeding difficulties, diarrhea, and failure to gain weight and grow at the expected rate (failure to thrive). Affected individuals usually develop a blood disorder called megaloblastic anemia. Megaloblastic anemia occurs when a person has a low number of red blood cells (anemia), and the remaining red blood cells are larger than normal (megaloblastic). The symptoms of this blood disorder may include decreased appetite, lack of energy, headaches, pale skin, and tingling or numbness in the hands and feet. People with hereditary folate malabsorption may also have a deficiency of white blood cells (leukopenia), leading to increased susceptibility to infections. In addition, they may have a reduction in the amount of platelets (thrombocytopenia), which can result in easy bruising and abnormal bleeding.

Some infants with hereditary folate malabsorption exhibit neurological problems such as developmental delay and seizures. Over time, untreated individuals may develop intellectual disability and difficulty coordinating movements (ataxia).  https://medlineplus.gov/genetics/condition/hereditary-folate-malabsorption

Clinical features

From HPO
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Malabsorption
MedGen UID:
811453
Concept ID:
C3714745
Finding
Impaired ability to absorb one or more nutrients from the intestine.
Athetosis
MedGen UID:
2115
Concept ID:
C0004158
Disease or Syndrome
A slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Athetosis involves continuous smooth movements that appear random and are not composed of recognizable sub-movements or movement fragments. In contrast to chorea, in athetosis, the same regions of the body are repeatedly involved. Athetosis may worsen with attempts at movement of posture, but athetosis can also occur at rest.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Dyskinesia
MedGen UID:
8514
Concept ID:
C0013384
Disease or Syndrome
A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements.
Peripheral neuropathy
MedGen UID:
18386
Concept ID:
C0031117
Disease or Syndrome
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Irritability
MedGen UID:
397841
Concept ID:
C2700617
Mental Process
A proneness to anger, i.e., a tendency to become easily bothered or annoyed.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Megaloblastic anemia, folate-responsive
MedGen UID:
440842
Concept ID:
C2749656
Finding
Folate-responsive megaloblastic anemia (MEGAF) is an autosomal recessive metabolic disorder characterized by megaloblastic anemia resulting from decreased folate transport into erythrocytes. Although serum levels of folate are normal, there is folate deficiency in tissues, including erythrocytes and possibly nerve cells. Serum homocysteine levels are increased and vitamin B12 levels may be decreased. Treatment with oral folate corrects the anemia and normalizes homocysteine (summary by Svaton et al., 2020)
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Basal ganglia calcification
MedGen UID:
234651
Concept ID:
C1389280
Pathologic Function
The presence of calcium deposition affecting one or more structures of the basal ganglia.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Leukopenia
MedGen UID:
6073
Concept ID:
C0023530
Disease or Syndrome
An abnormal decreased number of leukocytes in the blood.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Reduced blood folate concentration
MedGen UID:
42057
Concept ID:
C0016412
Disease or Syndrome
A reduced circulating concentration of folic acid, which is also known as vitamin B9.
Oral ulcer
MedGen UID:
57699
Concept ID:
C0149745
Disease or Syndrome
Erosion of the mucous mebrane of the mouth with local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCongenital defect of folate absorption
Follow this link to review classifications for Congenital defect of folate absorption in Orphanet.

Recent clinical studies

Etiology

Samodelov SL, Gai Z, Kullak-Ublick GA, Visentin M
Nutrients 2019 Oct 2;11(10) doi: 10.3390/nu11102353. PMID: 31581752Free PMC Article
Ebara S
Congenit Anom (Kyoto) 2017 Sep;57(5):138-141. Epub 2017 Jul 25 doi: 10.1111/cga.12233. PMID: 28603928
Hovdenak N, Haram K
Eur J Obstet Gynecol Reprod Biol 2012 Oct;164(2):127-32. Epub 2012 Jul 6 doi: 10.1016/j.ejogrb.2012.06.020. PMID: 22771225
Molloy AM
Int J Vitam Nutr Res 2002 Jan;72(1):46-52. doi: 10.1024/0300-9831.72.1.46. PMID: 11887752
Donnelly JG
Crit Rev Clin Lab Sci 2001 Jun;38(3):183-223. doi: 10.1080/20014091084209. PMID: 11451208

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
Ebara S
Congenit Anom (Kyoto) 2017 Sep;57(5):138-141. Epub 2017 Jul 25 doi: 10.1111/cga.12233. PMID: 28603928
Whitehead VM
Br J Haematol 2006 Jul;134(2):125-36. doi: 10.1111/j.1365-2141.2006.06133.x. PMID: 16846473
Kapadia CR
Gastroenterologist 1995 Dec;3(4):329-44. PMID: 8775094
Bruni J, Willmore LJ
Can J Neurol Sci 1979 Aug;6(3):345-9. doi: 10.1017/s0317167100023982. PMID: 487326

Therapy

Dolin CD, Deierlein AL, Evans MI
Fetal Diagn Ther 2018;44(3):161-165. Epub 2018 Aug 22 doi: 10.1159/000491786. PMID: 30134243
Ebara S
Congenit Anom (Kyoto) 2017 Sep;57(5):138-141. Epub 2017 Jul 25 doi: 10.1111/cga.12233. PMID: 28603928
Hovdenak N, Haram K
Eur J Obstet Gynecol Reprod Biol 2012 Oct;164(2):127-32. Epub 2012 Jul 6 doi: 10.1016/j.ejogrb.2012.06.020. PMID: 22771225
Corbeel L, Van den Berghe G, Jaeken J, Van Tornout J, Eeckels R
Eur J Pediatr 1985 Mar;143(4):284-90. doi: 10.1007/BF00442302. PMID: 3987728
Bruni J, Willmore LJ
Can J Neurol Sci 1979 Aug;6(3):345-9. doi: 10.1017/s0317167100023982. PMID: 487326

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
Zamek-Gliszczynski MJ, Zhang X, Mudunuru J, Du Y, Chen JL, Taskar KS, Huang J, Huang Y, Romach EH
Drug Metab Dispos 2019 Aug;47(8):890-898. Epub 2019 Jun 5 doi: 10.1124/dmd.119.087635. PMID: 31167838
Bruni J, Willmore LJ
Can J Neurol Sci 1979 Aug;6(3):345-9. doi: 10.1017/s0317167100023982. PMID: 487326

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
Zamek-Gliszczynski MJ, Zhang X, Mudunuru J, Du Y, Chen JL, Taskar KS, Huang J, Huang Y, Romach EH
Drug Metab Dispos 2019 Aug;47(8):890-898. Epub 2019 Jun 5 doi: 10.1124/dmd.119.087635. PMID: 31167838
Zinck JW, de Groh M, MacFarlane AJ
Am J Clin Nutr 2015 Jun;101(6):1295-304. Epub 2015 May 6 doi: 10.3945/ajcn.115.107219. PMID: 25948668
van der Put NM, van Straaten HW, Trijbels FJ, Blom HJ
Exp Biol Med (Maywood) 2001 Apr;226(4):243-70. doi: 10.1177/153537020122600402. PMID: 11368417
Boddie AM, Dedlow ER, Nackashi JA, Opalko FJ, Kauwell GP, Gregory JF 3rd, Bailey LB
Am J Clin Nutr 2000 Jul;72(1):154-8. doi: 10.1093/ajcn/72.1.154. PMID: 10871574

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
Ledowsky C, Mahimbo A, Scarf V, Steel A
Nutrients 2022 Jun 29;14(13) doi: 10.3390/nu14132715. PMID: 35807899Free 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
Jans G, Matthys C, Bogaerts A, Lannoo M, Verhaeghe J, Van der Schueren B, Devlieger R
Adv Nutr 2015 Jul;6(4):420-9. Epub 2015 Jul 15 doi: 10.3945/an.114.008086. PMID: 26178026Free PMC Article
Shankar P, Boylan M, Sriram K
Nutrition 2010 Nov-Dec;26(11-12):1031-7. Epub 2010 Apr 3 doi: 10.1016/j.nut.2009.12.003. PMID: 20363593

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...