Megaloblastic Anemias in Children
Introduction to Megaloblastic Anemias in Children
Megaloblastic anemias are a group of disorders characterized by the presence of abnormally large, immature erythrocytes (megaloblasts) in the bone marrow and peripheral blood. These anemias result from impaired DNA synthesis, most commonly due to deficiencies in vitamin B12 (cobalamin) or folate. In children, megaloblastic anemias can have significant impacts on growth and development, making early diagnosis and treatment crucial.
Key points:
- Megaloblastic anemias are macrocytic anemias caused by defective DNA synthesis
- Most common causes in children are vitamin B12 and folate deficiencies
- Can lead to severe hematological and neurological complications if left untreated
- Proper diagnosis and management are essential for optimal outcomes in pediatric patients
Etiology of Megaloblastic Anemias in Children
The etiology of megaloblastic anemias in children can be diverse, but the most common causes are nutritional deficiencies and genetic disorders affecting vitamin B12 or folate metabolism.
Vitamin B12 (Cobalamin) Deficiency
- Dietary deficiency: Rare in children, except in strict vegans or those with severe malnutrition
- Malabsorption:
- Intrinsic factor deficiency (congenital or juvenile pernicious anemia)
- Intestinal disorders: Crohn's disease, celiac disease, short bowel syndrome
- Gastric bypass surgery
- Genetic disorders:
- Imerslund-Gräsbeck syndrome (selective vitamin B12 malabsorption)
- Transcobalamin II deficiency
- Inborn errors of cobalamin metabolism (e.g., methylmalonic acidemia)
Folate Deficiency
- Dietary deficiency: More common in infants fed with goat's milk or in children with poor nutrition
- Increased requirements: Rapid growth, chronic hemolytic anemias, malignancies
- Malabsorption: Celiac disease, inflammatory bowel disease
- Medications: Anticonvulsants, methotrexate, trimethoprim
- Genetic disorders: Inborn errors of folate metabolism (e.g., methylenetetrahydrofolate reductase deficiency)
Other Causes
- Orotic aciduria (hereditary disorder of pyrimidine metabolism)
- Thiamine-responsive megaloblastic anemia syndrome
- Drug-induced: Antifolates, antimetabolites, some antiretroviral drugs
Clinical Manifestations of Megaloblastic Anemias in Children
The clinical presentation of megaloblastic anemias in children can vary depending on the underlying cause, severity, and duration of the deficiency. Symptoms may develop gradually and can affect multiple organ systems.
General Symptoms
- Pallor
- Fatigue and weakness
- Irritability
- Poor feeding or appetite
- Failure to thrive or growth retardation
- Developmental delays
Hematologic Manifestations
- Anemia: Symptoms may include tachycardia, dyspnea on exertion, and in severe cases, congestive heart failure
- Jaundice (due to ineffective erythropoiesis)
- Mild splenomegaly
- Neutropenia and thrombocytopenia (in severe cases)
Gastrointestinal Symptoms
- Glossitis (smooth, red tongue)
- Angular stomatitis
- Diarrhea
- Nausea and vomiting
Neurological Manifestations (more common in B12 deficiency)
- Developmental regression
- Hypotonia or hypertonia
- Seizures
- Ataxia
- Peripheral neuropathy
- Psychiatric symptoms: Irritability, apathy, depression
Dermatologic Findings
- Hyperpigmentation (more common in B12 deficiency)
- Vitiligo (associated with pernicious anemia)
It's important to note that infants with congenital causes of megaloblastic anemia may present with symptoms in the first few months of life, while those with acquired deficiencies may have a more insidious onset of symptoms.
Diagnosis of Megaloblastic Anemias in Children
Diagnosing megaloblastic anemias in children requires a comprehensive approach, including clinical evaluation, laboratory tests, and sometimes specialized investigations.
Initial Evaluation
- Thorough history: Dietary habits, family history, medications, associated symptoms
- Physical examination: Look for signs of anemia, growth parameters, neurological status
Laboratory Tests
- Complete Blood Count (CBC):
- Macrocytic anemia (elevated MCV)
- Decreased hemoglobin and hematocrit
- Possible neutropenia and thrombocytopenia
- Peripheral Blood Smear:
- Macrocytes, oval macrocytes
- Hypersegmented neutrophils
- Possible megaloblasts
- Reticulocyte Count: Usually low or normal despite anemia
- Serum Vitamin B12 and Folate Levels
- Methylmalonic Acid (MMA) and Homocysteine: Elevated in B12 deficiency
- Iron Studies: To rule out concomitant iron deficiency
Specialized Tests
- Bone Marrow Examination: Shows megaloblastic changes, not always necessary for diagnosis
- Schilling Test: To evaluate B12 absorption (rarely used now)
- Genetic Testing: For suspected inherited disorders of B12 or folate metabolism
- Anti-Intrinsic Factor and Anti-Parietal Cell Antibodies: For suspected pernicious anemia
- Metabolic Studies: Urine organic acids, plasma amino acids for inborn errors of metabolism
Additional Investigations
- Endoscopy and Small Bowel Biopsy: In cases of suspected malabsorption
- Neuroimaging: MRI in cases with significant neurological symptoms
The diagnosis of megaloblastic anemia should prompt a thorough investigation to determine the underlying cause, as this will guide appropriate treatment and management.
Treatment of Megaloblastic Anemias in Children
The treatment of megaloblastic anemias in children focuses on addressing the underlying cause and correcting the deficiency. The approach may vary depending on the etiology, severity of symptoms, and presence of complications.
General Principles
- Identify and treat the underlying cause
- Correct the specific vitamin deficiency
- Monitor response to treatment
- Address any complications
Vitamin B12 Deficiency Treatment
- Parenteral B12 Supplementation:
- Initial high-dose regimen: 1000 μg IM daily for 7 days
- Followed by 1000 μg weekly for 4-8 weeks
- Maintenance: 1000 μg monthly lifelong for pernicious anemia or other chronic causes
- Oral B12 Supplementation: May be considered in some cases, especially for dietary deficiency
- Dosage: 1000-2000 μg daily
- Not suitable for pernicious anemia or severe malabsorption
Folate Deficiency Treatment
- Oral Folate Supplementation:
- Typical dosage: 1-5 mg daily for 1-4 months
- Higher doses may be needed in malabsorption states
- Dietary Counseling: Encourage folate-rich foods
Management of Complications
- Severe Anemia: May require blood transfusion (packed red blood cells)
- Neurological Complications: Prompt initiation of B12 therapy; may require neurological follow-up
- Heart Failure: Supportive care and correction of anemia
Special Considerations
- Genetic Disorders: May require lifelong treatment and specialized management
- Malabsorption Disorders: Treat underlying condition (e.g., celiac disease, IBD)
- Drug-Induced Megaloblastic Anemia: Discontinue offending drug if possible, or adjust dosage
Monitoring and Follow-up
- Regular CBC to assess response to treatment
- Reticulocyte count typically increases within 3-5 days of starting treatment
- Monitor serum B12 or folate levels as appropriate
- Long-term follow-up for chronic conditions or genetic disorders
Early and appropriate treatment of megaloblastic anemias in children is crucial to prevent long-term complications, especially neurological sequelae in B12 deficiency. The treatment plan should be individualized based on the specific cause and the child's clinical status.
Prognosis of Megaloblastic Anemias in Children
The prognosis for children with megaloblastic anemias varies depending on the underlying cause, severity of the deficiency, duration of symptoms before diagnosis, and timely initiation of appropriate treatment.
General Prognosis
- Most cases have a good prognosis with appropriate treatment
- Hematological parameters typically improve rapidly with vitamin supplementation
- Complete resolution of anemia is usually seen within 6-8 weeks of starting treatment
Factors Affecting Prognosis
- Underlying Cause:
- Nutritional deficiencies: Excellent prognosis with proper supplementation and dietary changes
- Genetic disorders: May require lifelong management; prognosis depends on the specific disorder
- Malabsorption syndromes: Prognosis tied to management of the underlying condition
- Timing of Diagnosis and Treatment:
- Early diagnosis and treatment generally lead to better outcomes
- Delayed treatment, especially in B12 deficiency, may result in irreversible neurological damage
- Severity of Deficiency:
- Mild to moderate cases typically respond well to treatment
- Severe deficiencies may have a more prolonged recovery period
- Presence of Complications:
- Neurological complications may not fully resolve, especially if treatment is delayed
- Growth and developmental delays usually improve with treatment, but catch-up may take time
Long-term Outlook
- Most children with acquired deficiencies have an excellent long-term prognosis
- Regular follow-up is important to prevent recurrence
- Children with genetic disorders may require ongoing management and have variable long-term outcomes
- Neurodevelopmental outcomes in infants with congenital B12 deficiency depend on the timing of diagnosis and treatment initiation
Potential Complications
- Persistent neurological deficits in severe or prolonged B12 deficiency
- Growth and developmental delays may persist in some cases
- Increased risk of gastrointestinal malignancies in pernicious anemia (rare in children)
Overall, with proper diagnosis, treatment, and follow-up, most children with megaloblastic anemias have a favorable prognosis. However, prevention of deficiencies through proper nutrition and early recognition of symptoms is key to avoiding potential long-term complications.
Vitamin B12 Deficiency in Children
Vitamin B12 (cobalamin) deficiency is a significant cause of megaloblastic anemia in children. It can result from various factors, including dietary insufficiency, malabsorption, or genetic disorders.
Etiology
- Dietary deficiency:
- Exclusive breastfeeding by B12-deficient mothers
- Strict vegan or vegetarian diets without supplementation
- Severe malnutrition
- Malabsorption:
- Intrinsic factor deficiency (congenital or juvenile pernicious anemia)
- Gastric bypass surgery
- Crohn's disease, celiac disease, or other intestinal disorders
- Genetic disorders:
- Imerslund-Gräsbeck syndrome
- Transcobalamin II deficiency
- Inborn errors of cobalamin metabolism
Clinical Manifestations
- Hematologic:
- Pallor, fatigue, and weakness
- Tachycardia, dyspnea on exertion
- Jaundice (in severe cases)
- Neurologic:
- Developmental delay or regression
- Hypotonia or hypertonia
- Seizures
- Peripheral neuropathy
- Psychiatric symptoms (irritability, apathy)
- Gastrointestinal:
- Glossitis
- Anorexia, failure to thrive
- Diarrhea
- Dermatologic:
- Hyperpigmentation
- Vitiligo (in pernicious anemia)
Diagnosis
- Complete blood count: Macrocytic anemia, possible pancytopenia
- Peripheral blood smear: Macrocytes, hypersegmented neutrophils
- Serum B12 levels: Low (<200 pg/mL)
- Elevated methylmalonic acid and homocysteine levels
- Schilling test (rarely used now)
- Anti-intrinsic factor and anti-parietal cell antibodies (for pernicious anemia)
- Genetic testing for suspected inherited disorders
Treatment
- Parenteral B12 supplementation:
- Initial: 1000 μg IM daily for 7 days
- Followed by 1000 μg weekly for 4-8 weeks
- Maintenance: 1000 μg monthly for chronic conditions
- Oral B12 supplementation (in some cases):
- 1000-2000 μg daily
- Treatment of underlying cause (if identified)
- Dietary counseling and long-term supplementation as needed
Prognosis
With prompt diagnosis and appropriate treatment, the prognosis is generally good. However, delayed treatment, especially in infants, can lead to irreversible neurological damage. Regular follow-up and lifelong treatment may be necessary in some cases.
Folate Deficiency in Children
Folate deficiency is another common cause of megaloblastic anemia in children. It can occur due to inadequate intake, increased requirements, or impaired absorption.
Etiology
- Dietary insufficiency:
- Malnutrition
- Goat's milk feeding in infants
- Chronic alcoholism in adolescents
- Increased requirements:
- Rapid growth (infancy, adolescence)
- Chronic hemolytic anemias
- Malignancies
- Malabsorption:
- Celiac disease
- Inflammatory bowel disease
- Short bowel syndrome
- Medications:
- Anticonvulsants (e.g., phenytoin, phenobarbital)
- Methotrexate
- Trimethoprim
- Sulfasalazine
- Genetic disorders:
- Methylenetetrahydrofolate reductase (MTHFR) deficiency
- Other inborn errors of folate metabolism
Clinical Manifestations
- Hematologic:
- Pallor, fatigue, and weakness
- Tachycardia, dyspnea on exertion
- Gastrointestinal:
- Glossitis
- Angular stomatitis
- Diarrhea
- Growth retardation
- Neurologic (less common than in B12 deficiency):
- Irritability
- Developmental delays
- Depression (in adolescents)
Diagnosis
- Complete blood count: Macrocytic anemia
- Peripheral blood smear: Macrocytes, hypersegmented neutrophils
- Serum folate levels: Low (<3 ng/mL)
- Red blood cell folate levels: More accurate for chronic deficiency
- Elevated homocysteine levels (normal methylmalonic acid)
- Bone marrow examination: Megaloblastic changes (not always necessary)
Treatment
- Oral folate supplementation:
- 1-5 mg daily for 1-4 months
- Higher doses may be needed in malabsorption states
- Dietary counseling: Encourage folate-rich foods
- Treatment of underlying cause (if identified)
- Correction of concomitant iron deficiency, if present
Prognosis
The prognosis for folate deficiency is generally excellent with appropriate treatment. Hematological parameters typically improve within a few weeks of starting folate supplementation. However, in cases of chronic deficiency or underlying disorders, long-term management and follow-up may be necessary.
Imerslund-Gräsbeck Syndrome
Imerslund-Gräsbeck Syndrome (IGS), also known as Selective Vitamin B12 Malabsorption with Proteinuria, is a rare autosomal recessive disorder characterized by vitamin B12 deficiency and megaloblastic anemia.
Etiology
- Genetic mutations:
- CUBN gene (encoding cubilin)
- AMN gene (encoding amnionless)
- These mutations affect the cubam receptor complex, crucial for vitamin B12-intrinsic factor complex absorption in the terminal ileum
Clinical Manifestations
- Typically presents in early childhood (6 months to 5 years)
- Hematologic:
- Megaloblastic anemia
- Pallor, fatigue, and weakness
- Neurologic:
- Developmental delay
- Hypotonia
- Seizures (in some cases)
- Gastrointestinal:
- Failure to thrive
- Glossitis
- Renal:
- Mild to moderate proteinuria (hallmark of the syndrome)
Diagnosis
- Complete blood count: Macrocytic anemia
- Peripheral blood smear: Megaloblasts, hypersegmented neutrophils
- Low serum vitamin B12 levels
- Elevated methylmalonic acid and homocysteine levels
- Urine analysis: Proteinuria
- Normal intrinsic factor and parietal cell antibodies
- Genetic testing: Mutations in CUBN or AMN genes
- Schilling test (if available): Abnormal B12 absorption, not corrected by intrinsic factor administration
Treatment
- Lifelong parenteral vitamin B12 supplementation:
- Initial: 1000 μg IM daily for 7 days
- Followed by 1000 μg weekly for 4-8 weeks
- Maintenance: 1000 μg monthly
- Monitoring of renal function and proteinuria
- Genetic counseling for families
Prognosis
With early diagnosis and appropriate lifelong treatment, children with Imerslund-Gräsbeck Syndrome generally have a good prognosis. Regular B12 injections can prevent the development of anemia and neurological complications. However, the proteinuria typically persists despite treatment. Long-term follow-up is essential to monitor for potential renal complications and ensure adequate B12 supplementation.
Transcobalamin II Deficiency
Transcobalamin II deficiency is a rare autosomal recessive disorder characterized by the inability to transport vitamin B12 effectively in the bloodstream, leading to functional B12 deficiency and megaloblastic anemia.
Etiology
- Genetic mutations in the TCN2 gene, which encodes transcobalamin II
- Transcobalamin II is crucial for the transport of vitamin B12 from the intestine to tissues
Clinical Manifestations
- Usually presents in early infancy (first few weeks to months of life)
- Hematologic:
- Severe megaloblastic anemia
- Pancytopenia
- Neurologic:
- Developmental delay
- Seizures
- Microcephaly
- Gastrointestinal:
- Failure to thrive
- Vomiting and diarrhea
- Immunologic:
- Recurrent infections due to immunodeficiency
Diagnosis
- Complete blood count: Severe macrocytic anemia, often with neutropenia and thrombocytopenia
- Peripheral blood smear: Megaloblasts, hypersegmented neutrophils
- Normal or elevated serum vitamin B12 levels (paradoxical finding)
- Markedly elevated methylmalonic acid and homocysteine levels
- Low holotranscobalamin (active B12) levels
- Genetic testing: Mutations in the TCN2 gene
- Cultured fibroblasts may show decreased synthesis of transcobalamin II
Treatment
- Aggressive parenteral vitamin B12 supplementation:
- Initial: 1000 μg IM daily
- Maintenance: 1000 μg IM weekly or more frequently as needed
- Doses may need to be higher than in other forms of B12 deficiency
- Lifelong therapy is required
- Monitoring of hematological parameters and metabolites (methylmalonic acid, homocysteine)
- Supportive care:
- Blood transfusions may be necessary initially
- Nutritional support
- Management of infections
- Genetic counseling for families
Prognosis
The prognosis for children with transcobalamin II deficiency varies depending on how early the diagnosis is made and treatment is initiated. With prompt diagnosis and aggressive, lifelong B12 therapy, many children can achieve normal growth and development. However, if diagnosis is delayed, neurological sequelae may persist despite treatment. Regular follow-up is crucial to ensure adequate B12 supplementation and monitor for potential complications.
Inborn Errors of Cobalamin Metabolism
Inborn errors of cobalamin (vitamin B12) metabolism are a group of rare genetic disorders that affect the intracellular processing and utilization of vitamin B12. These disorders can lead to megaloblastic anemia and various neurological and metabolic abnormalities.
Types and Etiology
- cblA and cblB: Defects in mitochondrial methylmalonyl-CoA mutase
- cblC, cblD, cblF, cblJ: Defects affecting both methylcobalamin and adenosylcobalamin synthesis
- cblE and cblG: Defects in methionine synthase or its reductase
Clinical Manifestations
Symptoms can vary widely depending on the specific defect, but may include:
- Hematologic:
- Megaloblastic anemia (not always present)
- Pancytopenia
- Neurologic:
- Developmental delay or regression
- Seizures
- Hypotonia or hypertonia
- Ataxia
- Microcephaly
- Metabolic:
- Metabolic acidosis
- Hyperammonemia
- Hypoglycemia
- Ophthalmologic:
- Retinopathy (in cblC defect)
- Optic atrophy
- Other:
- Failure to thrive
- Vomiting and feeding difficulties
- Cardiovascular abnormalities (in some types)
Diagnosis
- Complete blood count: May show megaloblastic anemia
- Serum B12 levels: Usually normal or elevated
- Elevated methylmalonic acid and homocysteine levels (pattern depends on specific defect)
- Acylcarnitine profile: Elevated propionylcarnitine in some types
- Urine organic acid analysis: Elevated methylmalonic acid in some types
- Genetic testing: Mutations in specific genes associated with each type
- Enzyme assays on cultured fibroblasts (in some cases)
Treatment
Treatment varies depending on the specific defect but may include:
- Hydroxocobalamin injections: High-dose, frequent administration
- Betaine supplementation (for disorders affecting homocysteine metabolism)
- Dietary protein restriction (in some cases)
- L-carnitine supplementation
- Folate and other vitamin supplementation as needed
- Management of acute metabolic crises
- Supportive care and treatment of complications
Prognosis
Prognosis varies widely depending on the specific defect and the age at diagnosis and initiation of treatment. Some forms (like cblA and cblB) may respond well to treatment, while others (like cblC) can have significant long-term neurological and ophthalmological sequelae despite treatment. Early diagnosis through newborn screening and prompt, appropriate management are crucial for improving outcomes.
Orotic Aciduria
Orotic aciduria, also known as uridine monophosphate synthase (UMPS) deficiency, is a rare autosomal recessive disorder of pyrimidine metabolism. It can cause megaloblastic anemia and orotic acid crystalluria.
Etiology
- Mutations in the UMPS gene, which encodes uridine monophosphate synthase
- This enzyme catalyzes the final two steps in the de novo pyrimidine biosynthetic pathway
- Deficiency leads to accumulation of orotic acid and impaired pyrimidine nucleotide synthesis
Clinical Manifestations
- Hematologic:
- Megaloblastic anemia (often presenting in infancy)
- Neutropenia and thrombocytopenia may occur
- Growth and Development:
- Failure to thrive
- Developmental delay
- Urinary:
- Orotic acid crystalluria (may cause obstruction)
- Neurologic:
- Intellectual disability (in untreated cases)
- Immunologic:
- Increased susceptibility to infections
Diagnosis
- Complete blood count: Megaloblastic anemia
- Peripheral blood smear: Megaloblasts, hypersegmented neutrophils
- Urinalysis: Elevated orotic acid levels
- Normal serum folate and vitamin B12 levels
- Genetic testing: Mutations in the UMPS gene
- Enzyme assay: Decreased UMPS activity in erythrocytes or fibroblasts
Treatment
- Uridine supplementation:
- Oral uridine: 150-200 mg/kg/day in 4-6 divided doses
- Dosage adjusted based on clinical response and laboratory parameters
- Monitoring:
- Regular blood counts
- Urinary orotic acid levels
- Growth and development assessments
- Supportive care:
- Nutritional support
- Management of infections
- Genetic counseling for families
Prognosis
With early diagnosis and appropriate uridine supplementation, the prognosis for children with orotic aciduria is generally good. Hematological abnormalities typically resolve, and normal growth and development can be achieved. However, if diagnosis and treatment are delayed, some neurological sequelae may persist. Lifelong treatment with uridine is necessary, and regular follow-up is important to ensure optimal outcomes and adjust treatment as needed.
Megaloblastic Anemias in Children
- QUESTION: What are the two main causes of megaloblastic anemia?
ANSWER: Vitamin B12 deficiency and folate deficiency - QUESTION: Which of the following is a characteristic feature of megaloblastic anemia?
ANSWER: Macrocytosis (increased mean corpuscular volume) - QUESTION: What is the most common cause of vitamin B12 deficiency in children?
ANSWER: Inadequate dietary intake or malabsorption - QUESTION: Which of the following conditions can lead to folate deficiency in children?
ANSWER: Malabsorption syndromes, such as celiac disease - QUESTION: What is the primary function of vitamin B12 in the body?
ANSWER: DNA synthesis and red blood cell maturation - QUESTION: Which of the following is NOT a common symptom of megaloblastic anemia in children?
ANSWER: Jaundice - QUESTION: What is the most sensitive marker for tissue vitamin B12 deficiency?
ANSWER: Methylmalonic acid (MMA) - QUESTION: Which of the following tests can help differentiate between vitamin B12 and folate deficiency?
ANSWER: Serum homocysteine levels - QUESTION: What is the recommended daily intake of vitamin B12 for children aged 4-8 years?
ANSWER: 1.2 mcg - QUESTION: Which of the following is a rich dietary source of folate?
ANSWER: Leafy green vegetables - QUESTION: What is the most common treatment for vitamin B12 deficiency in children?
ANSWER: Intramuscular vitamin B12 injections - QUESTION: How long does it typically take for reticulocyte count to increase after starting treatment for megaloblastic anemia?
ANSWER: 3-5 days - QUESTION: Which of the following is a potential neurological complication of untreated vitamin B12 deficiency?
ANSWER: Subacute combined degeneration of the spinal cord - QUESTION: What is the term for the presence of hypersegmented neutrophils in the peripheral blood smear?
ANSWER: Neutrophil hypersegmentation - QUESTION: Which of the following conditions can cause vitamin B12 deficiency in breastfed infants?
ANSWER: Maternal pernicious anemia - QUESTION: What is the most common cause of folate deficiency in infants?
ANSWER: Inadequate dietary intake - QUESTION: Which of the following is NOT a typical finding in megaloblastic anemia?
ANSWER: Microcytosis - QUESTION: What is the recommended daily intake of folate for children aged 9-13 years?
ANSWER: 300 mcg - QUESTION: Which of the following medications can interfere with folate metabolism?
ANSWER: Methotrexate - QUESTION: What is the term for the presence of oval macrocytes in the peripheral blood smear?
ANSWER: Macroovalocytes - QUESTION: Which of the following is NOT a common side effect of oral folate supplementation?
ANSWER: Nausea and vomiting - QUESTION: What is the primary storage form of vitamin B12 in the body?
ANSWER: Methylcobalamin - QUESTION: Which of the following conditions can mimic megaloblastic anemia in children?
ANSWER: Myelodysplastic syndrome - QUESTION: What percentage of total body vitamin B12 is typically stored in the liver?
ANSWER: About 50% - QUESTION: Which of the following is a sign of severe folate deficiency in infants?
ANSWER: Failure to thrive - QUESTION: What is the term for the presence of nucleated red blood cells in the peripheral blood smear?
ANSWER: Erythroid hyperplasia - QUESTION: Which of the following is NOT a risk factor for megaloblastic anemia in children?
ANSWER: Iron overload - QUESTION: What is the recommended first-line screening test for vitamin B12 deficiency in children?
ANSWER: Serum vitamin B12 level - QUESTION: Which of the following is a late sign of vitamin B12 deficiency?
ANSWER: Glossitis (inflammation of the tongue) - QUESTION: What is the most common cause of megaloblastic anemia in adolescents?
ANSWER: Nutritional deficiency (inadequate intake of vitamin B12 or folate)
