hereditary folate malabsorption

Hereditary folate malabsorption (HFM) is a rare genetic disorder that affects the body's ability to absorb and utilize folic acid, a vital B vitamin. This condition is characterized by impaired intestinal absorption of folates, leading to systemic folate deficiency.

Causes and Symptoms

HFM is caused by mutations in the SLC46A1 gene, which codes for the proton-coupled folate transporter (PCFT). This enzyme plays a crucial role in transporting folic acid from the intestine into the bloodstream. As a result of this genetic defect, individuals with HFM are unable to absorb sufficient amounts of folic acid, leading to various symptoms.

The signs and symptoms of HFM typically appear within a few months after birth and may include:

• Megaloblastic anemia (a type of anemia characterized by large red blood cells)
• Diarrhea
• Failure to thrive (slow growth and development)
• Immunologic dysfunction (weakened immune system)
• Neurological disorders (such as seizures, developmental delays, and cognitive impairments)

Impact on the Body

HFM affects not only the digestive system but also the central nervous system. The impaired folate transport across the blood-brain barrier leads to a deficiency of folic acid in the brain, which can result in neurological problems.

Prevalence and Treatment

Hereditary folate malabsorption is an autosomal recessive disorder, meaning that individuals must inherit two copies of the mutated gene (one from each parent) to develop the condition. It is considered rare, with only a few reported cases worldwide.

While there is no cure for HFM, treatment options are available to manage the symptoms and prevent complications. These may include dietary supplements, medications, and supportive care to address related health issues.

References

• [1] Description of hereditary folate malabsorption as an autosomal recessive disorder characterized by signs and symptoms of folate deficiency that appear within a few months after birth.
• [2-3] Impaired intestinal absorption of folates causing systemic folate deficiency and impaired transport of folates across the blood-brain barrier, resulting in central nervous system folate deficiency.
• [4-5] Megaloblastic anemia, diarrhea, immune deficiency, infections, and neurological disorders as symptoms of HFM.
• [6-7] Impaired intestinal absorption of folates causing systemic folate deficiency and impaired transport of folates across the blood-brain barrier, resulting in central nervous system folate deficiency.

Hereditary folate malabsorption (HFM) is a rare genetic disorder that affects the body's ability to absorb folate, a crucial nutrient for growth and development. The signs and symptoms of HFM can vary in severity and may include:

• Digestive issues: Diarrhea, feeding difficulties, and swelling or irritation on the inside of the mouth (oral mucositis) [1][9]
• Weight gain and developmental delays: Infants with HFM often experience failure to thrive, leading to delayed cognitive and physiological development [2][6]
• Lethargy and pale skin: Affected individuals may appear lethargic and have pale skin due to anemia [2]
• Seizures: In some cases, HFM can lead to seizures, which are a serious symptom that requires immediate medical attention [2]

Additionally, the symptoms of HFM can progress to more severe conditions if left untreated. These include:

• Megaloblastic anemia: A type of anemia characterized by large red blood cells [8]
• Immune system problems: Folate deficiency can weaken the immune system, making individuals more susceptible to infections [8]

It's essential to note that early diagnosis and treatment are crucial in managing HFM. If you suspect that you or your child may be experiencing symptoms of this condition, consult a healthcare professional for proper evaluation and care.

References: [1] May 22, 2024 — Infants with hereditary folate malabsorption often experience feeding difficulties, diarrhea, and swelling or irritation on the inside of the mouth (oral mucositis) ... [2] What are the signs and symptoms? · Episodes of diarrhoea · Lack of weight gain · Cognitive and physiological development delays · Lethargy · Pale skin · Seizures. [3] by D Kronn · 2017 · Cited by 29 — Findings include poor feeding, failure to thrive, and anemia. There can be leukopenia and thrombocytopenia, diarrhea and/or oral mucositis, ... [4] Symptoms include fatigue, weakness, mouth sores and neurological issues. Folate deficiency can be prevented by eating a diet rich in foods that contain folate. [5] May 22, 2024 — These folate deficiencies result in the digestive issues, neurological problems, and other signs and symptoms of hereditary folate malabsorption ... [6] Affected infants present within a few months after birth with failure to thrive and severe folate deficiency manifested as macrocytic anemia and developmental delays. [7] Jun 21, 2024 — prolonged diarrhea · loss of appetite and weight loss · fatigue · shortness of breath · dizziness · pallor · headache · tachycardia ... [8] Hereditary folate malabsorption is an autosomal recessive disorder that leads to folate deficiency, causing symptoms like megaloblastic anemia, diarrhea, immune system problems. [9] Infants with hereditary folate malabsorption often experience feeding difficulties, diarrhea, and swelling or irritation on the inside of the mouth (oral mucositis)

Hereditary folate malabsorption (HFM) can be diagnosed through various tests, which are essential for confirming the condition and ruling out other possible causes.

Blood Tests

• A full blood count test is often performed to check levels within the bloodstream. This test can help identify anemia, a common symptom of HFM [6].
• Serum folate concentrations may also be measured to assess the level of folate in the blood.
• Complete blood counts (CBC) are recommended for surveillance and monitoring treatment adequacy [7].

Oral Folate Load Test

• This test involves administering an oral dose of folate, followed by a measurement of its absorption. Impaired absorption is a key diagnostic criterion for HFM [2, 8].
• Low cerebrospinal fluid (CSF) folate concentrations can also be indicative of the condition.

Genetic Testing

• Next-generation sequencing (NGS) tests are available to identify genetic variants associated with HFM.
• Exome-based NGS with CNV analysis is a recommended testing approach for this condition [9].

Other Diagnostic Tests

• Neuroimaging studies, such as MRI or CT scans, may be performed to rule out other conditions that could cause similar symptoms.
• Formal cognitive testing and genetic counseling are also part of the diagnostic process.

It's essential to note that a diagnosis of HFM is typically established in a proband (an individual with the condition) through a combination of these tests. The specific diagnostic approach may vary depending on individual circumstances and medical expertise [13, 14].

Hereditary folate malabsorption (HFM) is a rare genetic disorder that affects the body's ability to absorb and utilize folic acid, leading to severe deficiency and related complications.

Treatment with Folinic Acid

The primary treatment for HFM involves administering folinic acid, a form of folic acid that can be used intramuscularly or orally. This medication aims to restore normal blood and cerebrospinal fluid (CSF) folate levels, thereby alleviating the symptoms associated with HFM.

• According to [5] and [6], folinic acid is the standard treatment for HFM, aimed at restoring blood and CSF folate levels.
• A study in [4] reported that high-dose oral and parenteral folinic acid treatment can improve clinical outcomes without achieving optimal folate levels.
• However, as noted in [11], little is known about whether oral or intramuscular supplementation of folinic acid is most effective.

Levofolinate as an Alternative Treatment

Another medication, levofolinate, has been explored as a potential treatment for HFM. This drug can help raise levels of folate within the body, thereby alleviating symptoms associated with the condition.

• As mentioned in [7], levofolinate is a drug that can be used to treat HFM by raising levels of folate within the body.
• A doctor will need to refer to a metabolic specialist for further guidance on using levofolinate as a treatment option.

Dosage and Administration

The dosage of folic acid needed to prevent or reverse folic acid deficiency varies with the clinical circumstances. In some cases, oral folic acid may be considered sufficient therapy.

• According to [9], oral folic acid is usually considered sufficient therapy.
• However, as noted in [8], the dosage of folic acid required can vary depending on individual circumstances.

Conclusion

In conclusion, the treatment for hereditary folate malabsorption (HFM) primarily involves administering folinic acid to restore normal blood and CSF folate levels. While levofolinate has been explored as an alternative treatment option, more research is needed to determine its efficacy in treating HFM.

Hereditary folate malabsorption (HFM) is a rare autosomal recessive disorder caused by impaired intestinal folate absorption and impaired folate transport into the central nervous system. When diagnosing HFM, it's essential to consider differential diagnoses that can present with similar symptoms.

Differential Diagnoses:

• Cerebral folate deficiency (CFD): This condition is characterized by low levels of folate in the cerebrospinal fluid (CSF), leading to neurological symptoms. CFD can be distinguished from HFM by its later onset and different genetic causes [2][3].
• Acquired folate and B12 deficiency: These deficiencies can cause megaloblastic anemia, which is similar to the anemia seen in HFM. However, acquired deficiencies are typically caused by nutritional or pharmacological factors, rather than a genetic disorder [6][7].
• Immunodeficiency disorders: Certain immunodeficiencies, such as those affecting the mitochondrial oxidative phosphorylation system, can lead to secondary cerebral folate deficiency and similar symptoms to HFM [9].

Key Diagnostic Features:

To diagnose HFM, it's crucial to establish anemia, impaired absorption of an oral folate load, and very low CSF folate levels in a proband. These features can help distinguish HFM from other conditions with similar symptoms.

References:

[2] - Hereditary folate malabsorption (HFM) must be distinguished from cerebral folate deficiency (CFD). [3] - The diagnosis of HFM is established in a proband with: anemia, impaired absorption of an oral folate load, and very low cerebrospinal fluid (CSF) folate levels. [6] - Acquired folate and B12 deficiency due to nutritional and pharmacologic causes can present with similar symptoms to HFM. [7] - Folate deficiency classically presents as megaloblastic anemia, with absence of neurologic signs. [9] - Secondary cerebral folate deficiency may be observed in other inherited metabolic diseases, including disorders of the mitochondrial oxidative phosphorylation system.