Vitamin D Deficiency (Rickets) in Children
Introduction to Vitamin D Deficiency (Rickets) in Children
Rickets is a metabolic bone disease characterized by impaired mineralization of bone matrix in children. It primarily occurs due to vitamin D deficiency, although other causes exist. This condition affects the growing skeleton, leading to various skeletal deformities and growth abnormalities.
Key points:
- Rickets is most common in children aged 3 months to 18 months
- It's a global health issue, affecting both developed and developing countries
- The prevalence has increased in recent years due to reduced sun exposure and dietary factors
- Early recognition and treatment are crucial to prevent long-term complications
Etiology of Rickets
The primary causes of rickets include:
- Vitamin D deficiency (most common cause):
- Inadequate sunlight exposure
- Insufficient dietary intake
- Malabsorption syndromes
- Calcium deficiency
- Phosphate deficiency
- Genetic disorders:
- X-linked hypophosphatemic rickets
- Vitamin D-dependent rickets type I and II
- Chronic kidney disease
Risk factors include:
- Dark skin pigmentation
- Exclusive breastfeeding without vitamin D supplementation
- Living in higher latitudes
- Cultural practices limiting sun exposure
- Certain medications (e.g., anticonvulsants, glucocorticoids)
Pathophysiology of Rickets
The pathophysiology of rickets involves:
- Vitamin D metabolism:
- Vitamin D3 (cholecalciferol) is synthesized in the skin upon UVB exposure
- Vitamin D2 (ergocalciferol) is obtained from diet
- Both forms are hydroxylated in the liver to 25-hydroxyvitamin D
- Further hydroxylation occurs in the kidneys to form 1,25-dihydroxyvitamin D (active form)
- Effects of vitamin D deficiency:
- Decreased intestinal calcium and phosphate absorption
- Reduced serum calcium levels
- Increased parathyroid hormone (PTH) secretion
- PTH-induced phosphaturia and bone resorption
- Impaired mineralization of bone matrix
- Bone changes:
- Widening and cupping of metaphyses
- Softening and bowing of weight-bearing bones
- Delayed closure of fontanelles
- Craniotabes (softening of skull bones)
Clinical Presentation of Rickets
The clinical features of rickets vary with age and severity:
Skeletal manifestations:
- Craniotabes (in infants <3 months)
- Delayed fontanelle closure
- Frontal bossing
- Rachitic rosary (enlarged costochondral junctions)
- Harrison's groove (horizontal depression along lower chest)
- Widening of wrists and ankles
- Bowing of legs (genu varum) or knock-knees (genu valgum)
- Delayed dentition
- Enamel hypoplasia
Non-skeletal manifestations:
- Hypocalcemic seizures (in severe cases)
- Muscle weakness and hypotonia
- Growth retardation
- Delayed motor development
- Irritability
- Increased susceptibility to infections
Diagnosis of Rickets
Diagnosis of rickets is based on clinical, biochemical, and radiographic findings:
1. Clinical examination
- Assessment of skeletal deformities
- Evaluation of growth and development
2. Laboratory tests
- Serum calcium: Normal or low
- Serum phosphate: Low
- Serum alkaline phosphatase: Elevated
- Serum 25-hydroxyvitamin D: Low (<20 ng/mL)
- Serum parathyroid hormone (PTH): Elevated
- Urine calcium: Low
3. Radiographic findings
- Cupping, fraying, and widening of metaphyses
- Widening of growth plates
- Osteopenia
- Cortical thinning
- Bowing of long bones
4. Bone biopsy (rarely needed)
- Increased osteoid thickness
- Decreased mineralization
Treatment of Rickets
The treatment of rickets aims to correct the underlying deficiency and heal bone lesions:
1. Vitamin D supplementation
- Oral vitamin D2 or D3: 2000-5000 IU daily for 2-3 months
- Alternatively, a single high dose of 300,000-600,000 IU (stoss therapy)
- Maintenance dose: 400-1000 IU daily
2. Calcium supplementation
- 30-75 mg/kg/day of elemental calcium in divided doses
3. Phosphate supplementation (if needed)
- In cases of hypophosphatemic rickets
4. Treatment of underlying conditions
- Management of malabsorption syndromes
- Treatment of renal tubular disorders
5. Monitoring
- Regular follow-up of clinical symptoms
- Serum calcium, phosphate, and alkaline phosphatase levels
- Repeat radiographs to assess healing
Prevention of Rickets
Preventive measures for rickets include:
1. Vitamin D supplementation
- For breastfed infants: 400 IU/day from birth
- For formula-fed infants: 400 IU/day if consuming less than 1 liter of formula
- For older children and adolescents: 600-1000 IU/day
2. Adequate sunlight exposure
- 10-30 minutes of midday sun exposure, 2-3 times per week
- Considering factors like skin pigmentation and latitude
3. Dietary sources of vitamin D
- Fatty fish (salmon, tuna)
- Egg yolks
- Fortified foods (milk, cereals)
4. Calcium-rich diet
- Dairy products
- Leafy green vegetables
- Fortified foods
5. Screening high-risk groups
- Children with dark skin
- Those living in higher latitudes
- Children with chronic diseases affecting vitamin D metabolism
Complications of Rickets
If left untreated, rickets can lead to various complications:
1. Skeletal complications
- Permanent bone deformities
- Short stature
- Increased risk of fractures
- Osteomalacia in adulthood
2. Dental problems
- Enamel defects
- Increased risk of dental caries
- Malocclusion
3. Neurological complications
- Seizures (due to hypocalcemia)
- Tetany
- Developmental delays
4. Cardiorespiratory issues
- Respiratory infections
- Pulmonary insufficiency (in severe chest deformities)
5. Other complications
- Growth retardation
- Muscle weakness
- Increased susceptibility to infections
Introduction to Types of Rickets
Rickets is a condition characterized by impaired mineralization of growing bone and cartilage. While the most common form is nutritional rickets due to vitamin D deficiency, several other types exist, each with distinct genetic and biochemical features. Understanding these variations is crucial for accurate diagnosis and appropriate management.
The main categories of rickets include:
- Nutritional Rickets (Vitamin D and/or Calcium deficiency)
- Genetic forms of Vitamin D-Dependent Rickets
- Hypophosphatemic Rickets (various genetic forms)
- Other rare forms (e.g., Hypophosphatasia)
Each type has unique pathophysiology, clinical presentation, and treatment approaches, which will be detailed in the following sections.
Nutritional Rickets
Etiology
- Vitamin D deficiency (most common)
- Calcium deficiency
- Combined vitamin D and calcium deficiency
Pathophysiology
In vitamin D deficiency:
- Decreased intestinal calcium absorption
- Hypocalcemia
- Secondary hyperparathyroidism
- Increased bone resorption and decreased mineralization
In calcium deficiency:
- Inadequate calcium intake or absorption
- Secondary hyperparathyroidism
- Increased 1,25-dihydroxyvitamin D production
- Impaired mineralization due to lack of calcium
Clinical Features
- Skeletal deformities (bowed legs, knock knees)
- Rachitic rosary
- Craniotabes in infants
- Growth retardation
- Muscle weakness
Diagnosis
- Low serum 25-hydroxyvitamin D (<20 ng/mL)
- Elevated alkaline phosphatase
- Low or normal serum calcium and phosphate
- Elevated PTH
- Characteristic radiographic changes
Treatment
- Vitamin D supplementation (2000-5000 IU daily for 2-3 months)
- Calcium supplementation (30-75 mg/kg/day)
- Maintenance therapy and nutritional counseling
Vitamin D-Dependent Rickets Type 1 (VDDR1)
Etiology
- Autosomal recessive disorder
- Mutations in the CYP27B1 gene (encoding 1α-hydroxylase)
Pathophysiology
- Impaired conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D
- Decreased intestinal calcium absorption
- Hypocalcemia and secondary hyperparathyroidism
Clinical Features
- Onset in infancy or early childhood
- Growth retardation
- Hypotonia
- Skeletal deformities similar to nutritional rickets
Diagnosis
- Low serum calcium and phosphate
- Elevated alkaline phosphatase
- Normal or elevated 25-hydroxyvitamin D
- Low 1,25-dihydroxyvitamin D
- Genetic testing for CYP27B1 mutations
Treatment
- Lifelong calcitriol (1,25-dihydroxyvitamin D) supplementation
- Calcium supplementation as needed
- Regular monitoring of serum calcium, phosphate, and PTH
Vitamin D-Dependent Rickets Type 2 (VDDR2)
Etiology
- Autosomal recessive disorder
- Mutations in the VDR gene (encoding vitamin D receptor)
Pathophysiology
- End-organ resistance to 1,25-dihydroxyvitamin D
- Impaired intestinal calcium absorption
- Hypocalcemia and secondary hyperparathyroidism
Clinical Features
- Early onset (first year of life)
- Severe rickets
- Alopecia (in some cases)
- Growth retardation
- Hypocalcemic seizures may occur
Diagnosis
- Low serum calcium and phosphate
- Elevated alkaline phosphatase
- Very high 1,25-dihydroxyvitamin D levels
- Genetic testing for VDR mutations
Treatment
- High-dose calcitriol (up to 2 μg/kg/day)
- High-dose calcium supplementation (1-3 g/day)
- Some cases may require intravenous calcium infusions
- Regular monitoring of serum calcium, phosphate, and urinary calcium excretion
X-Linked Hypophosphatemic Rickets (XLH)
Etiology
- X-linked dominant disorder
- Mutations in the PHEX gene
Pathophysiology
- Increased production of fibroblast growth factor 23 (FGF23)
- FGF23-mediated phosphate wasting in the kidneys
- Impaired 1α-hydroxylation of vitamin D
Clinical Features
- Lower limb deformities (often asymmetrical)
- Short stature
- Dental abscesses
- Bone pain and arthropathy in adults
Diagnosis
- Low serum phosphate
- Normal serum calcium
- Elevated alkaline phosphatase
- Normal or slightly elevated PTH
- Elevated FGF23 levels
- Genetic testing for PHEX mutations
Treatment
- Oral phosphate supplementation
- Calcitriol or alfacalcidol
- Regular monitoring of serum phosphate, calcium, PTH, and urinary calcium
- Burosumab (anti-FGF23 monoclonal antibody) for severe cases
- Orthopedic management for skeletal deformities
Autosomal Dominant Hypophosphatemic Rickets (ADHR)
Etiology
- Autosomal dominant disorder
- Mutations in the FGF23 gene
Pathophysiology
- Gain-of-function mutations in FGF23
- Increased circulating levels of FGF23
- Renal phosphate wasting
- Impaired 1α-hydroxylation of vitamin D
Clinical Features
- Variable age of onset (childhood to adulthood)
- Lower limb deformities
- Bone pain
- Dental abnormalities
- Fatigue and muscle weakness
Diagnosis
- Low serum phosphate
- Normal serum calcium
- Elevated alkaline phosphatase
- Elevated or inappropriately normal FGF23 levels
- Genetic testing for FGF23 mutations
Treatment
- Similar to XLH: phosphate supplementation and calcitriol
- Dose adjustments based on age and severity
- Regular monitoring of biochemical parameters
- Consideration of burosumab in severe cases
Autosomal Recessive Hypophosphatemic Rickets (ARHR)
Etiology
- Autosomal recessive disorder
- Two main types:
- ARHR1: Mutations in the DMP1 gene
- ARHR2: Mutations in the ENPP1 gene
Pathophysiology
- Increased FGF23 production and/or signaling
- Renal phosphate wasting
- Impaired 1α-hydroxylation of vitamin D
Clinical Features
- Similar to other forms of hypophosphatemic rickets
- Lower limb deformities
- Dental abnormalities
- Short stature
- ARHR2 may also present with arterial calcifications
Diagnosis
- Low serum phosphate
- Normal serum calcium
- Elevated alkaline phosphatase
- Elevated FGF23 levels
- Genetic testing for DMP1 or ENPP1 mutations
Treatment
- Phosphate supplementation
- Calcitriol or alfacalcidol
- Regular monitoring of biochemical parameters
- Management of complications (e.g., dental issues, skeletal deformities)
Hypophosphatasia
Etiology
- Autosomal recessive or dominant disorder
- Mutations in the ALPL gene (encoding tissue-nonspecific alkaline phosphatase)
Pathophysiology
- Deficiency of tissue-nonspecific alkaline phosphatase (TNSALP)
- Accumulation of inorganic pyrophosphate (PPi), an inhibitor of mineralization
- Impaired hydroxyapatite crystal formation
Clinical Features
- Variable severity and age of onset
- Perinatal: severe skeletal hypomineralization, respiratory failure
- Infantile: failure to thrive, hypotonia, skeletal deformities
- Childhood: premature loss of deciduous teeth, short stature, bone pain
- Adult: recurrent fractures, osteoarthropathy
Diagnosis
- Low serum alkaline phosphatase (hallmark finding)
- Elevated serum pyridoxal 5'-phosphate (vitamin B6)
- Elevated urinary phosphoethanolamine
- Normal or elevated serum calcium and phosphate
- Radiographic features: poor mineralization, metaphyseal irregularities
- Genetic testing for ALPL mutations
Treatment
- Enzyme replacement therapy: Asfotase alfa (recombinant alkaline phosphatase)
- Supportive care:
- Pain management
- Physical therapy
- Dental care
- Orthopedic interventions for fractures and deformities
- Avoiding bisphosphonates (may worsen the condition)
- Careful monitoring of serum calcium levels
- Genetic counseling for affected families
Prognosis
- Varies widely depending on the severity and age of onset
- Perinatal and infantile forms can be life-threatening without treatment
- Milder forms may have a normal lifespan with appropriate management
- Enzyme replacement therapy has significantly improved outcomes for severe cases
Vitamin D Deficiency (Rickets) in Children
- What is the primary cause of nutritional rickets in children?
Vitamin D deficiency - Which age group is most commonly affected by vitamin D deficiency rickets?
Infants and toddlers - What is the main source of vitamin D for most children?
Sunlight exposure (UVB radiation) - Which bone deformity is characteristic of rickets in the legs of toddlers?
Bowing of the legs (genu varum) - What is the recommended daily intake of vitamin D for infants 0-12 months old?
400 IU (10 μg) - Which biochemical marker is elevated in active rickets?
Alkaline phosphatase - What is the classic radiographic finding in rickets?
Cupping and fraying of the metaphyses - Which population group is at higher risk of vitamin D deficiency rickets?
Dark-skinned individuals living in northern latitudes - What is the role of calcium in the development of rickets?
Calcium deficiency can exacerbate vitamin D deficiency rickets - Which cranial deformity is associated with rickets in infants?
Craniotabes (softening of the skull bones) - What is the active form of vitamin D in the body?
1,25-dihydroxyvitamin D (calcitriol) - Which organ is responsible for the final activation of vitamin D?
Kidney - What is the most common clinical presentation of rickets in infants?
Delayed motor development and skeletal deformities - Which biochemical abnormality is typically seen in vitamin D deficiency rickets?
Low serum 25-hydroxyvitamin D levels - What is the recommended treatment dose of vitamin D for severe rickets?
50,000 IU weekly for 6-8 weeks, followed by maintenance therapy - Which complication of severe rickets can lead to breathing difficulties?
Chest wall deformities (rachitic rosary) - What is the role of parathyroid hormone in vitamin D deficiency?
Increased secretion to maintain calcium homeostasis - Which nutrient deficiency often coexists with vitamin D deficiency in rickets?
Calcium deficiency - What is the recommended maintenance dose of vitamin D for children at risk of deficiency?
600-1000 IU daily - Which growth parameter is most affected in children with chronic vitamin D deficiency?
Height (linear growth) - What is the role of phosphate in the pathophysiology of rickets?
Decreased renal phosphate reabsorption leads to hypophosphatemia - Which non-skeletal symptom can be associated with severe vitamin D deficiency in children?
Muscle weakness and hypotonia - What is the typical serum calcium level in children with vitamin D deficiency rickets?
Low to low-normal - Which dental abnormality is associated with vitamin D deficiency in children?
Enamel hypoplasia - What is the recommended screening test for vitamin D deficiency?
Serum 25-hydroxyvitamin D level - Which age group is at risk of vitamin D deficiency due to reduced skin synthesis?
Adolescents - What is the role of vitamin D in calcium absorption?
Enhances intestinal calcium absorption - Which chronic medical condition increases the risk of vitamin D deficiency in children?
Malabsorption syndromes (e.g., celiac disease, cystic fibrosis) - What is the recommended daily intake of vitamin D for children 1-18 years old?
600 IU (15 μg) - Which biomarker is used to monitor the response to vitamin D treatment in rickets?
Alkaline phosphatase levels
