Non-nutritional rickets: Approach, precision medicine, and outcomes

Table 5 Hereditary forms of calciopenic rickets[2,125]

Condition	Gene (chromosome)	Mode of inheritance	Ca dose	Activated vitamin D (calcitriol/alfacalcidol) dose	Calcifediol dose	Vitamin D (cholecalciferol) dose	Biochemical response
VDDR1A	CYP27B1 (12q13)	AR	30-75 mg/kg/day; (0.5-3 g/day) elemental Ca	Calcitriol: 10-100 ng/kg/day; 0.3-2 μg/day. Alfacalcidol: 10-100 ng/kg/day; 0.5-3 μg/day	Not useful	Not useful	ALP: 3-12 months; Ca: 5 months; PTH: 6 months (may not normalize)
VDDR1B	CYP2R1 (11p15)	AR/AD	30-75 mg/kg/day; (0.5-2 g/day) elemental Ca)	Calcitriol: 10-100 ng/kg/day; 0.3-2 μg/day. Alfacalcidol: 10-100 ng/kg/day; 0.5-3 μg/day	15-50 μg/day	Heterozygous: 5000-10000 IU/day. Homozygous: 600000 every 3 months	3 months
VDDR2A	VDR (12q13)	AR	3-5 g/day; 400-1400 mg/m2/day	10-400 ng/kg/day; 5-60 μg/day (for both)	20-200 μg/day	Not helpful	6-12 months, may not occur in all children
VDDR2B	Unknown (post-receptor defect)	NK (isolated cases)
VDDR3	CYP3A4 (7q22)	AD (usually de novo mutations)	May be required (30-75 mg/kg/day)	Calcitriol: Low limit: 1 μg/day, upper limit: Not defined. Alfacalcidiol: Low limit: 2 μg/day, upper limit: Not defined	Low limit: 50 μg/day, upper limit: Not defined (metabolized rapidly)	10000-50000IU per day	3 months

VDDR1A: Vitamin D dependent rickets type 1A; VDDR1B: Vitamin D dependent rickets type 1B; VDDR2A: Vitamin D dependent rickets type 2A; VDDR2B: Vitamin D dependent rickets type 2B; VDDR3: Vitamin D dependent rickets type 3; CYP27B1: Cytochrome P450 family 27 subfamily B member 1; CYP2R1: Cytochrome P450 family 2 subfamily R member 1; VDR: Vitamin D receptor; CYP3A4: Cytochrome P450 family 3 subfamily A member 4; AR: Autosomal recessive; AD: Autosomal dominant; Ca: Calcium; ALP: Alkaline phosphatase; PTH: Parathyroid hormone.