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D52.1 – Drug-Induced Folate Deficiency
D52.1 is the ICD-10 code for drug-induced folate deficiency. Certain medications interfere with the absorption or metabolism of folic acid, leading to a clinically relevant deficiency.
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D52.1 is the ICD-10 code for drug-induced folate deficiency. Certain medications interfere with the absorption or metabolism of folic acid, leading to a clinically relevant deficiency.
What is D52.1?
D52.1 is an ICD-10 diagnostic code that describes drug-induced folate deficiency. Folic acid (also known as folate or vitamin B9) is an essential B vitamin required for cell division, the production of red blood cells, and DNA synthesis. When certain medications interfere with the absorption or metabolism of folic acid, a clinically significant deficiency can develop.
Causes
Drug-induced folate deficiency is caused by medications that interfere with folate metabolism in various ways:
- Methotrexate: Inhibits the enzyme dihydrofolate reductase, blocking the conversion of folate into its active form.
- Antiepileptic drugs (e.g., phenytoin, phenobarbital, primidone): Increase hepatic folate degradation and reduce intestinal absorption.
- Trimethoprim and pyrimethamine: Also inhibit dihydrofolate reductase, disrupting folate metabolism.
- Sulfonamides: Impair folate synthesis and utilization.
- Oral contraceptives: May lower blood folate levels with long-term use.
- Metformin: Can reduce the intestinal absorption of folate and vitamin B12 with prolonged use.
Symptoms
Folate deficiency can develop gradually and affect multiple organ systems:
- Megaloblastic anemia: Formation of enlarged, immature red blood cells that cannot function properly.
- Fatigue, weakness, and general malaise
- Pallor of the skin and mucous membranes
- Angular cheilitis (cracks at the corners of the mouth) and a sore or burning tongue
- Difficulties with concentration and memory
- During pregnancy: increased risk of neural tube defects in the unborn child
Diagnosis
The diagnosis of drug-induced folate deficiency involves several steps:
- Complete blood count: Detection of megaloblastic anemia with an elevated mean corpuscular volume (MCV).
- Serum folate: Measurement of folate levels in the blood (normal range typically above 3 ng/ml).
- Red blood cell folate: Reflects longer-term folate stores in the body and is more informative than serum levels alone.
- Homocysteine: An elevated blood homocysteine level is a sensitive marker for folate or vitamin B12 deficiency.
- Medication history: A thorough review of all medications taken to establish the causal relationship.
Treatment
Treatment depends on the underlying cause and the severity of the deficiency:
- Folic acid supplementation: Oral administration of folic acid (typically 1–5 mg per day), or parenterally in severe cases. Dosage is adjusted individually.
- Medication adjustment: Where possible, the causative drug is reduced in dose or replaced with an alternative.
- Leucovorin (folinic acid): Often given alongside methotrexate therapy as an active form of folate that bypasses the enzymatic block.
- Dietary measures: Increased intake of folate-rich foods (e.g., leafy green vegetables, legumes, whole grains) as a complementary measure.
- Regular monitoring: Ongoing surveillance of blood counts and folate/homocysteine levels during therapy with folate-affecting medications.
Prevention
In patients at known risk of drug-induced folate deficiency – for example, during long-term therapy with antiepileptics or methotrexate – clinical guidelines recommend prophylactic folic acid supplementation. This is especially important for women of childbearing age, as folate deficiency in early pregnancy significantly increases the risk of neural tube defects in the developing fetus.
References
- World Health Organization (WHO): Serum and red blood cell folate concentrations for assessing folate status in populations. WHO, Geneva, 2015. www.who.int
- Bailey LB, Stover PJ, McNulty H et al.: Biomarkers of Nutrition for Development – Folate Review. Journal of Nutrition, 145(7):1636S–1680S, 2015. doi:10.3945/jn.114.206599
- Green R, Miller JW: Folate Deficiency Beyond Megaloblastic Anemia: Hyperhomocysteinemia and Other Manifestations of Dysfunctional Folate Status. Seminars in Hematology, 36(1):47–64, 1999.
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