Hypervitaminosis in Children

Hypervitaminosis refers to a condition of abnormally high storage levels of vitamins, which can lead to toxic symptoms. While the body has mechanisms to excrete excess water-soluble vitamins (B and C), fat-soluble vitamins (A, D, E, and K) are stored in the liver and adipose tissue, making them more prone to accumulation and toxicity. In children, this often results from excessive supplementation, accidental ingestion, or food faddism.

Hypervitaminosis A

Vitamin A toxicity can occur from the ingestion of large doses of preformed vitamin A (retinol or retinyl esters). It is distinct from carotenemia, which is caused by excess beta-carotene intake.

Etiology

• Acute Toxicity: Ingestion of large doses, typically greater than 50,000 IU/day, often seen with accidental ingestion of supplements.
• Chronic Toxicity: Daily ingestion of doses exceeding physiological needs (e.g., >6,000 µg or ~20,000 IU in children) for weeks or months. Common causes include excessive use of vitamin supplements, fish liver oils, or therapeutic preparations for acne.
• "Gulf Syndrome": A specific historical reference to hypervitaminosis A and D resulting from excessive intake of attractive fish oil pearls brought from Middle-East countries.

Clinical Manifestations

• Acute Toxicity:
  • CNS: Symptoms of raised intracranial pressure (pseudotumor cerebri) including vomiting, irritability, bulging fontanel (in infants), diplopia, and severe headache.
  • General: Stupor, limited motion, and vertigo.
• Chronic Toxicity:
  • Dermatological: Dry, itchy, desquamating skin; fissuring at the corners of the mouth (cheilosis); alopecia (hair loss) and coarsening of hair; yellow-orange dislocation of palms and soles (if associated with carotenemia).
  • Musculoskeletal: Painful swelling of long bones due to subperiosteal bone formation, bone tenderness, and arthralgia.
  • Hepatic: Hepatomegaly and splenomegaly; can progress to cirrhosis and portal hypertension.
  • General: Anorexia, failure to thrive (lack of weight gain), and fatigue.
• Teratogenicity: High doses of vitamin A (isotretinoin/retinoic acid) during early pregnancy can cause spontaneous abortions and severe congenital malformations (craniofacial abnormalities).

Diagnostic Findings

• Serum Levels: Elevated serum vitamin A levels (retinyl esters are elevated while retinol-binding protein is saturated).
• Radiology: Hyperostosis (cortical thickening) affecting the middle of the shafts of long bones, particularly the ulna and tibia (long, wavy cortical hyperostosis). Metaphyseal changes are typically absent.
• Bone Scans: May show increased uptake before radiographic changes appear.

Management

• Cessation: Immediate withdrawal of vitamin A sources leads to rapid subsidence of symptoms, though skeletal changes may take months to resolve.
• Supportive Care: Symptomatic treatment for elevated intracranial pressure or skin lesions.

Carotenemia

• Definition: Yellow-orange pigmentation of the skin caused by excessive intake of carotene-rich foods (e.g., carrots, papaya, squash).
• Differentiation: Distinguished from jaundice by the absence of scleral icterus (sclerae remain white).
• Clinical Course: Benign condition; skin color returns to normal 2–6 weeks after reducing carotene intake.

Hypervitaminosis D

Vitamin D toxicity is the most potentially serious hypervitaminosis due to its severe renal and cardiovascular sequelae. It is usually iatrogenic or due to accidental overdose.

Etiology

• Excessive Supplementation: Misuse of high-dose supplements (e.g., stoss therapy errors), unmonitored use of calcitriol (active vitamin D), or over-fortification of milk/foods.
• Hypersensitivity: Conditions like William's syndrome or idiopathic infantile hypercalcemia where children are sensitive to normal or slightly elevated vitamin D levels.
• Mechanism: Toxicity is never caused by excessive sunlight exposure due to cutaneous regulation.

Pathophysiology

• Excess vitamin D leads to uncontrolled intestinal calcium absorption and bone resorption.
• This results in hypercalcemia and hypercalciuria.
• High serum calcium suppresses Parathyroid Hormone (PTH).

Clinical Manifestations

Symptoms are primarily those of hypercalcemia:

• Gastrointestinal: Nausea, vomiting, anorexia, constipation, abdominal pain, and pancreatitis.
• Renal: Polyuria and polydipsia (nephrogenic diabetes insipidus), nephrocalcinosis (calcium deposits in kidney), nephrolithiasis, and progressive renal insufficiency.
• Neurological: Hypotonia, irritability, lethargy, stupor, and confusion.
• Cardiovascular: Hypertension, shortened QT interval, arrhythmias.
• Metastatic Calcification: Calcification of soft tissues, including blood vessels, cornea (band keratopathy), and kidneys.

Investigations

• Serum Biochemistry:
  • Calcium: Marked hypercalcemia.
  • Phosphate: Hyperphosphatemia (distinct from hyperparathyroidism where phosphate is low).
  • ALP: Normal or low.
  • PTH: Suppressed/Low.
  • Vitamin D metabolites: Markedly elevated 25-hydroxyvitamin D (>100 ng/mL). Levels of 1,25-dihydroxyvitamin D may be normal due to renal regulation.
• Imaging: Renal ultrasound may show nephrocalcinosis. X-rays may show metastatic calcifications or increased bone density.

Management

• Immediate: Discontinue vitamin D and calcium supplements. Avoid sun exposure.
• Hydration: Aggressive IV hydration with normal saline to expand volume and promote calciuresis.
• Diuretics: Loop diuretics (e.g., Furosemide) to increase urinary calcium excretion (after rehydration).
• Glucocorticoids: Prednisone (1–2 mg/kg/day) reduces intestinal calcium absorption and is highly effective in vitamin D toxicity.
• Bisphosphonates: Inhibit osteoclast-mediated bone resorption.
• Dialysis: Hemodialysis with low-calcium dialysate for life-threatening hypercalcemia refractory to other measures.

Hypervitaminosis E

Vitamin E is relatively non-toxic compared to other fat-soluble vitamins.

• Clinical Features:
  • High doses (>1000 mg/day) can antagonize vitamin K, leading to a bleeding diathesis (prolonged prothrombin time).
  • Gastrointestinal symptoms: Nausea, diarrhea, flatulence.
  • Constitutional: Fatigue, muscle weakness, headache.
  • Neonates: Excessive administration in preterm infants has been associated with necrotizing enterocolitis (NEC) and sepsis in historical cohorts.
• Management: Discontinuation of the supplement leads to rapid resolution.

Hypervitaminosis K

Naturally occurring Vitamin K1 (phylloquinone) is generally safe. Toxicity is associated with the water-soluble synthetic analogue, Vitamin K3 (menadione/Synkavit).

• Clinical Features:
  • Hemolysis: Induces oxidative stress leading to hemolytic anemia, particularly in G6PD deficient individuals and preterm infants.
  • Hyperbilirubinemia: Resulting from hemolysis, increasing the risk of kernicterus (bilirubin encephalopathy) in neonates.
  • Liver: Hepatotoxicity with large doses.
• Prevention: Use of natural Vitamin K1 (phylloquinone) for hemorrhagic disease of the newborn prophylaxis has largely eliminated this complication.

Hypervitaminosis of Water-Soluble Vitamins

While generally excreted in urine, massive doses ("megavitamin therapy") can cause toxicity.

• Vitamin C (Ascorbic Acid):

  • GI: Abdominal pain, osmotic diarrhea, nausea.
  • Renal: Increased oxalate excretion leading to renal stones (nephrolithiasis).
  • Metabolic: Can precipitate hemolysis in G6PD deficiency. Large doses can interfere with B12 absorption.
  • Rebound Scurvy: Sudden withdrawal after chronic high intake can precipitate scurvy in the fetus/neonate.

• Niacin (Vitamin B3):

  • Cutaneous: Intense flushing, burning sensation, and pruritus (histamine release).
  • Hepatic: Hepatotoxicity, jaundice, and elevated enzymes with sustained high doses.
  • Metabolic: Hyperglycemia and hyperuricemia.

• Pyridoxine (Vitamin B6):

  • Neurological: Sensory neuropathy (ataxia, numbness, paresthesia) with chronic intake of >200–500 mg/day. It creates a dependency state; withdrawal can cause seizures in infants.

• Folate:

  • Masks hematological signs of Vitamin B12 deficiency (pernicious anemia) while neurological damage progresses.

Summary Table of Key Toxicities

References

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