Untitled Quiz

Hypocalcemia Definition

• Hypocalcemia is defined as a total serum calcium level below 8.5 mg/dL (corrected for albumin) or a serum calcium level below 4.65 mg/dL (1.16 mmol/L)
• Corrected total calcium level = measured total calcium level + (0.8 × [4 − measured albumin level in g/dL])
• A total serum calcium level between 7.6 mg/dL to 8.5 mg/dL may be symptomatic
• Hypocalcemia below the reference range can be asymptomatic or severe

Calcium Metabolism and Function

• 99% of the body's calcium is stored in bones
• Serum calcium can be present in free (ionized, 50%) or bound form (either bound to proteins, 40% or complexed with bicarbonate, citrate, and phosphate, 10%)
• Calcium plays critical roles in:
  • Cellular function regulation by acting as a messenger system
  • Activating cellular enzyme cascades
  • Smooth muscle and myocardial contraction
  • Nerve impulse conduction
  • Secretory activity of exocrine glands

Magnesium

• Magnesium is found in bone (50%) and soft tissues (50%)
• Half of the magnesium in bone is readily exchangeable with the extracellular fluid, acting as a buffer against changes in extracellular magnesium concentration

Phosphate Metabolism

• 85% of phosphate is located in the mineral phase of bone, while the rest is found in inorganic or organic form in extracellular and intracellular compartments
• Phosphate levels in the blood are regulated by growth factors, such as insulin-like growth factor 1 (IGF1) and hormones of bone mineralization
• Phosphate plays a crucial role in numerous kinase and phosphatase regulatory cascades

Etiology: Early Onset Neonatal Hypocalcemia

• Occurs within 48-72 hours of birth
• Causes:
  • Prematurity: inadequate nutritional intake, decreased parathyroid hormone response to vitamin D, increased calcitonin levels
  • Birth asphyxia: delayed feeding, increased calcitonin production, increased endogenous phosphate load
  • Infants of diabetic mothers: maternal magnesium depletion causes hypomagnesemia in the fetus, leading to functional hypoparathyroidism and hypocalcemia in the infant
  • Intrauterine growth restriction: decreased transplacental passage of calcium

Etiology: Late-Onset Neonatal Hypocalcemia

• Occurs 3-7 days after birth, occasionally as late as 6 weeks
• Causes:
  • Exogenous phosphate load: common in developing countries, due to phosphate-rich formula or cow's milk feeding
  • Vitamin D deficiency: vitamin D insufficiency or deficiency and hypomagnesemia
  • DiGeorge syndrome: primary immunodeficiency disorder characterized by cellular (T-cell) deficiency, facial features, congenital heart disease, and hypocalcemia

Etiology: Hypocalcemia in Infants and Children

• Hypoparathyroidism
  • Post surgical hypoparathyroidism: most common cause of chronic hypocalcemia
    • Transient: parathyroid function recovers within 12 months after parathyroid surgery
    • Permanent: hypoparathyroidism persists beyond 12 months after onset
  • Aplasia or hypoplasia of parathyroid gland: DiGeorge syndrome, Haploinsufficiency of GATA3 transcription factor causes HDR syndrome
  • Autoimmune parathyroiditis: autoimmune polyendocrine syndrome type 1
  • Infiltrative lesions: Hemosiderosis, Wilson disease, thalassemia
  • Idiopathic causes

Genetic Parathyroid Disorders

• Disorders of Parathyroid Gland Formation:
  • Tbx1 transcription factor loss in 22q11 deletion syndrome (DiGeorge syndrome, velocardiofacial syndrome) likely causes hypoparathyroidism in this syndrome
  • CHARGE syndrome: rare disorders with phenotypic overlap between 21q11DS and HDR, caused by SEMAE3 or CHD7 mutations
  • Haploinsufficiency of the transcription factor GATA3: causes the HDR (hypoparathyroidism, deafness, and renal dysplasia) syndrome