Rickets

Overview

Rickets is an impairment of bone mineralization prior to epiphyseal closure. The most common cause of rickets is Vitamin D deficiency (does not occur naturally in foods, needs fortification/supplementation).

• Classes of causes of rickets
  • Vitamin D deficiency or receptor mutation
  • Calcium deficiency (more of the congenital causes)
  • Phosphate deficiency

Rickets manifests as skeletal malformations

• Risk factors for Rickets
  • Premature infants
  • Unbalanced infant nutrition: protracted exclusive Breast Feeding, vegetarian diets
  • No vitamin D supplementation in formula infants
  • Maternal vitamin D deficiency
  • Lack of sun exposure
• Signs and symptoms
  • Genu varum (bowlegedness, young children)
  • Genu valgus (knock-knees, older children)
  • Kyphoscoliosis
  • Pronounced lumbar lordosis
  • Craniotabes (soft skull)
  • Costochondral swelling (”rachitic rosary”)
  • Metaphyseal cupping (esp of the wrist and ankles)
  • Tendency to fracture (Greenstick fracture)
  • Dental problems e.g. delayed eruption
  • Muscle weakness (d/t hypocalcemia)
  • Harrison’s groove (Very specific sign of rickets)
  • Parietal and frontal bossing
  • Late closing of fontanelles (check occipital)
• Investigations
  • Basic Metabolic Panel, including Ca, PO4, and Mg levels
  • Urine electrolytes (Ca and PO4)
  • 25-OH-Vitamin D and Calcitriol levels
  • PTH levels
  • CBC
  • Radiographs e.g. AP and Lateral X-ray of the wrist: Metaphyseal Cupping
  • Assess for specific nutritional deficiency

Vitamin D-related rickets

Vitamin D deficiency rickets

MCC of rickets wordwide. Common in developing countries where Viamin D fortified foods are not readily available. Dx is based on nutritional Hx, radiograpbs, and lab findings. Consider malabsorption if the pt has appropriate diet and/or there sx consistent with malabsorption (fat in stool, FTT, low weight etc.)

• Investigations
  • 25-OH-Vit D: low
  • Calcitriol: low
  • Serum calcium: variable (may be compensated d/t inc PTH)
  • Serum phosphate: high
  • PTH: high
  • Urine calcium: low
  • Urine phosphate: high
• Treatment
  • Vitamin D replacement
  • Patient and parent education (make sure they get Vitamin D supplementation with their diet)

Vitamin D dependent rickets, Type 1

Caused by 1-OHase deficiency, which converts 25-OH-Vit D to 1,25-OH-Vit D. Signs and symptoms of Vitamin D deficiency despite getting sufficiency dietary Vitamin D. Major differential is Malabsorption or CKD (more obvious in the History).

• Investigations
  • 25-OH Vit D: normal or high
  • Calcitriol: low
  • Serum calcium: variable (may be compensated d/t inc PTH)
  • Serum phosphate: high
  • PTH: high
  • Urine calcium: low
  • Urine phosphate: high
• Treatment
  • Vitamin D replacement with Calcitriol

Vitamin D dependent rickets, Type 2

Caused by deactivating mutation of the calcitiol receptor, preventing the body from responding to calcitriol despite high levels. AR.

Signs and symptoms of vitamin D deficiency despite getting sufficiency dietary Vitamin D. Typically present in infancy and alopecia may be present (reflects the severity of their Vit D deficiency). Difficult to treat.

• Investigations:
  • Calcitriol: high
  • Serum calcium: variable (may be compensated d/t inc PTH)
  • Serum phosphate: high
  • PTH: high
  • Urine calcium: low
  • Urine phosphate: high
• Treatment
  • Megadoses of calcitriol and calcium (not all children will respond)

Hypocalcemia-related rickets

Renal osteomalacia

This is rickets superimposed on Chronic Kidney Disease (CKD). Child will have a H/O of renal failure in addition to signs and symptoms of bone disease

• What 2 problems in CKD predispose the child to rickets
  • 1-OHase deficiency (Reduced production of calcitriol)
  • Impaired tubular resorption of calcium (Calcium wasting)
• Investigations
  • Calcitriol: Low
  • 25-OH-Vit D: normal
  • Serum calcium: low
  • Serum phosphate: high
  • U/E/C: elevated creatinine
• Treatment
  • Cacitriol replacement
  • Low phosphate diet
  • Phosphate binder

Hypocalcemia ricket

Often coexits with Vitamin-D deficiency and manifests in children who are breast feeding without calcium supplementation OR children who are consuming unfortified formulas. Malabsorption can be a differential (of calcium and Vitamin D). Can look like renal osteomalacia, however the child will have normal renal function.

• Investigations
  • Serum calcium: low
  • Urine calcium: low
  • Urine phosphate: high
  • U/E/Cs: normal
• Treatment
  • Adequate dietary calcium/Supplementation
  • Treat any concurrent deficiency

Hypophosphatemia-related rickets

Very difficult to get phosphate deficiency based on diet alone because it is very ubiquitous.

X-linked hypophosphatemic rickets (XLHR)

Caused by overproduction of FGF-23 which stimulates phosphate excretion and inhibits 1-OHase. Will have a FHx (little boys, brother and father of mother etc.)

• Investigations
  • 25-OH-Vit D: normal
  • Calcitriol: Low
  • Serum phosphate: Low
  • Urinary phosphate: High
• Treatment
  • Calcitiol
  • Phosphate supplementation

Autosomal dominant hereditary rickets (ADHR) and Autosomal recessive hereditary rickets (ARHR)

Simiar profile to and management to XLHR.

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH)

Due to defective sodium-phosphate cotransporter in the proximal tubule which causes Hypophosphatemia → and increased PTH → high serum calcium and serum low serum phosphate. Urine calcium and phosphate wil be high.

• Treatment
  • Phosphate supplementation

Other causes of hypophosphatemia

• High FGF-23/Phosphantoins (looks like XLHR)
  • Tumor-induced osteomalacia
  • McCune-Albright syndrome (overall reduction in hormones)
  • Epidermal nevus syndrome
  • Neurofibromatosis
• Fanconi syndrome (proximal tubular defect; episodes of metablic acidsosi d/t bicarbonate loss)
• Dent’s disease