Folate Malabsorption, Hereditary

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OMIM 57 229050 Orphanet 59 ORPHA90045 ICD10 via Orphanet 34 D52.8 UMLS via Orphanet 74 C0342705

MedGen 42 C0342705 KEGG 37 H01252 SNOMED-CT via HPO 69 258211005 197927001 26284000 45534005 25786006 277843001 398979000 228156007 247578003 91138005 128613002 246545002 313307000 84757009 91175000 85102008 398151007 398152000 224958001 86854008 36440009 432788009 302215000 415116008 165517008 127034005 84828003 53165003 267060006 62315008 16932000 16331000 235595009 698065002 79890006 44913001 58593005 17944005 234532001 74035001 119250001 302226006 386033004 42658009 9748009 7847004 more UMLS 73 C0342705

NIH Rare Diseases : ⁵³ The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 90045Disease definitionHereditary folate malabsorption (HFM) is an inherited disorder of folate transport characterized by a systemic and central nervous system (CNS) folate deficiency manifesting as megaloblastic anemia, failure to thrive, diarrhea and/or oral mucositis, immunologic dysfunction and neurological disorders.EpidemiologyThe prevalence is unknown. Approximately 30 cases have been reported to date.Clinical descriptionDisease onset usually occurs a few months after birth. Manifestations include failure to thrive, diarrhea and/or mouth ulcers, various neurological manifestations (motor impairment, seizures, developmental delay, cognitive and behavioral disorders), megaloblastic anemia and hypoimmunoglobulinemia. Megaloblastic anemia is the primary manifestation of HFM and can be very severe if untreated. Hypoimmunoglobulinemia results in unusual infections with Pneumocystis jiroveccii, C. difficile and cytomegalovirus (CMV) which can be recurrent and life-threatening in undiagnosed infants. Neurological manifestations may be the presenting symptoms in some but are absent in others. Seizures, if present, begin in infancy or later in childhood. Intracranial calcifications have been observed in some.EtiologyHFM is caused by mutations in the SLC46A1 gene found on chromosome 17q11.2 which encodes the proton-coupled folate transporter (PCFT). PCFT is essential for intestinal folate absorption and transport of folates across the blood-cerebrospinal fluid (CSF) barrier. A defect in this protein leads to a systemic folate and CNS folate deficiency. Infants cannot absorb adequate folate from breast milk/formula and become deficient once their stores accumulated during gestation are exhausted.Diagnostic methodsDiagnosis is based on clinical and laboratory findings. It is confirmed by findings of an impaired absorption of an oral folate load (even after correction of serum folate concentration) and a low CSF folate concentration (0-1.5nM). Bone marrow biopsy confirms the presence of megaloblastic anemia. Sequence analysis of the SLC46A1 coding region can identify any mutations present in the gene, also confirming diagnosis of HFM.Differential diagnosisThe immunodeficiency seen in HFM may resemble severe combined immune deficiency (SCID; see this term). Other differential diagnoses include methionine synthase deficiency with megaloblastic anemia and developmental delay, formiminoglutamic aciduria, tyrosinemia type 1, methylenetetrahydrofolate reductase deficiency and erythroleukemia (see these terms).Antenatal diagnosisAntenatal diagnosis is possible via prenatal testing. Screening of newborns with a family history of HFM allows for early diagnosis and treatment with folate immediately after birth, before symptoms occur.Genetic counselingHFM is inherited autosomal recessively. Genetic counseling is possible.Management and treatmentHigh dose oral or parenteral 5-formyltetrahydrofolate (5-formylTHF) and oral L-5-methyltetrahydrofolate (L-5-methylTHF) are the two types of reduced folates used to treat HFM. Dosage is monitored and adjusted (individualized for each patient) so that the CSF folate levels remain within the normal range (around 100nM in infants-2 year olds). Folic acid should not be used as it binds to folate receptors and blocks folate transport. If anemia is severe, a transfusion may be necessary. Early treatment with reduced folates before the appearance of symptoms can prevent the metabolic consequences of HFM. Patients should have regular blood tests to monitor complete blood count, serum and CSF folate and homocysteine concentrations and serum immunoglobulin concentrations.PrognosisWith proper treatment the prognosis is good and reversal of most of the systemic consequences of the disease is usually achieved. Only when untreated is the prognosis poor.Visit the Orphanet disease page for more resources.

MalaCards based summary : Folate Malabsorption, Hereditary, also known as hereditary folate malabsorption, is related to hemifacial microsomia and epilepsy occipital calcifications, and has symptoms including ataxia, athetosis and diarrhea. An important gene associated with Folate Malabsorption, Hereditary is SLC46A1 (Solute Carrier Family 46 Member 1), and among its related pathways/superpathways are Vitamin digestion and absorption and Mineral absorption. Affiliated tissues include testes, bone marrow and brain, and related phenotypes are recurrent urinary tract infections and glossitis

Genetics Home Reference : ²⁵ 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.

OMIM : ⁵⁷ 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). (229050)

UniProtKB/Swiss-Prot : ⁷⁵ Hereditary folate malabsorption: Rare autosomal recessive disorder characterized by impaired intestinal folate absorption with folate deficiency resulting in anemia, hypoimmunoglobulinemia with recurrent infections, and recurrent or chronic diarrhea. In many patients, neurological abnormalities such as seizures or mental retardation become apparent during early childhood, attributed to impaired transport of folates into the central nervous system. When diagnosed early, the disorder can be treated by administration of folate. If untreated, it can be fatal and, if treatment is delayed, the neurological defects can become permanent.

Wikipedia : ⁷⁶ Hereditary folate malabsorption (HFM - OMIM #229050) is a rare autosomal recessive disorder caused by... more...

GeneReviews: NBK1673

Clinical features from OMIM:

229050

Search Clinical Trials , NIH Clinical Center for Folate Malabsorption, Hereditary

Search GEO for disease gene expression data for Folate Malabsorption, Hereditary.