Mineral disorders

Calcium, phosphorus, vitamin D, and the hormones that regulate them are very important in skeletal development and mineralization. Abnormalities in these can disrupt calcium homeostasis and therefore cause disorders of mineral metabolism or skeletal disorders of childhood.

Calcium homeostasis

calcium homeostasis
Figure 15. Low serum calcium stimulates release of PTH from the parathyroid glands. PTH stimulates calcium release
from bone and the kidneys to reabsorb calcium. The kidneys also excrete phosphorus and produce more vitamin D.
Vitamin D stimulates intestinal absorption of calcium.

Hypocalcemia

Etiologies:

Types

Physiology

Examples

Neonatal Hypocalcemia
  • Exaggeration of physiologic decrease in serum calcium
  • Insufficient PTH due to immature parathyroid hormone or immature kidney response; more commonly seen in premature infants
  • Late onset more frequently associated with hyperphosphatemia
  • Early - birth to 3 days of life
  • Late - onset at 1 week of life
    • Congenital hypoparathyroidism
    • Maternal hypercalcemia
    • Phosphorus overload from cow's milk formula
    • Uremia
    • Congenital Vitamin D deficiency

Illness
  • Relative hypoparathyroidism
  • Hypercalcitoninemia
  • Burn injuries
  • Cardiac surgery

Hypoparathyroidism
  • Improper parathyroid gland formation
  • Destruction of parathyroid glands
  • Impaired parathyroid gland function
  • Parathyroid and thymus hypoplasia: DiGeorge Syndrome
  • Parathyroid dysgenesis: Kenny-Caffey Syndrome and Sanjad-Sakati Syndrome
  • Parathyroid aplasia or dysplasia: inactivation of GCM2 gene
  • APS type 1: triad of hypoparathyroidism, adrenal insufficiency, and mucocutaneous candidiasis
  • PTH gene mutations
  • Anti-CaSR antibodies
  • Mitochondrial disease

Table 6. Etiologies of Hypocalcemia

Diagnosis: Measure serum calcium and vitamin-25OHD with corresponding phosphorus and PTH. Also, magnesium and alkaline phosphatase should also be checked. An ECG should be obtained to evaluate for changes related to hypocalcemia (i.e. prolonged QT interval).

Treatment:

Hypercalcemia

Etiologies:

Types

Physiology

Examples

Familial hypocalciuric hypercalcemia

Hypercalcemia with elevated PTH, normal phosphorus, normal magnesium, elevated alkaline phosphatase, and low urinary calcium

Mutation of CaSR gene

Williams Syndrome

Elevated calcium and calcitriol

Facial anomalies, cardiac and renal defects, hyperacusis, and cognitive impairment

Hyperparathyroidism

Elevated calcium, elevated PTH, low phosphorus, and elevated calcitriol

Childhood neck irradiation

Immobilization

Decreased skeletal mineral

Elevated serum calcium and urinary calcium

Prolonged immobilization

Weightless space travel

Malignancy

Osteoclastic activity leading to excessive calcium release from bone

 Lymphomas

Squamous cell carcinoma

Breast cancer

Renal cell carcinom, bladder carcinoma

Multiple myeloma

Table 7. Etiologies of Hypercalcemia

Diagnosis: Measure calcium, phosphorus, PTH, magnesium, Vitamin-25OHD, and alkaline phosphatase. ECG will show shortened ST segment and heart block.

Treatment: Increase urinary excretion of sodium with furosemide. Start calcitonin to indirectly inhibit osteoclastic bone resoprtion or inhibit bone resorption directly with bisphosphonates.

Metabolic Bone Disease

Rickets occurs when there is defective mineralization of the epiphyseal growth plate. Although there are different causes of rickets, all forms show characteristic widening and flaring of the epiphyses. 

Etiologies:

 

Causes

Examples

Vitamin D deficiency
  • Exclusively breast-fed infants for at least 6 months
  • Lack of exposure to direct sunlight
  • GI disorders: biliary atresia, CF, IBD, and celiac disease
  • Liver disease
  • Drugs that induce CYP450 enzymes

Calcium Deficiency Rickets

Unclear underlying causes

Rickets of prematurity
  • TPN dependence
  • Incomplete calcium attrition normally attained in third trimester

Hypophosphatemic Rickets
  • X-linked hypophosphatemia
  • Autosomal dominant/recessive   hypophosphatemic rickets
  • Hereditary hypophosphatemic rickets with hypercalciuria

 Table 8. Etiologies of Metabolic Bone Disease.  

 


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