Table 2.
Characteristics and therapeutic response of the recently published cases of toddlers with HVDRR and VDR gene mutations.
| Genotype | Demographic data | Clinical data | Biochemical data | Drug(s) used | Treatment duration | Response to treatment | References |
|---|---|---|---|---|---|---|---|
| Arg80Gln missense mutation in the VDR DNA-binding domain | 30-month-old girl Consanguineous parents from North Africa Child's country of origin-Belgium |
Total neonatal alopecia Stunted growth Developmental delay Upper and lower extremity rachitic deformities |
Hypocalcemia Hypophosphatemia Very high ALP and PTH Low 25(OH)D2 Very high 1,25(OH)2 D3 |
Vitamin D + oral calcium iv calcium 45 mg/kg/d Cinacalcet 0.27 mg/kg/d |
1 month 4 months 2 months |
No improvement No improvement Clinical improvement with biological and radiological healing |
Current case report |
| Homozygote stop-codon mutation (c.148 C >T) in exon 2 of the VDR gene Homozygote stop-codon mutation (c.148 C >T) in exon 2 of the VDR gene |
2.5-year-old girl 4-month-old girl Consanguineous parents from Turkey Children's country of origin-Turkey |
Alopecia Failure to thrive Seizures Lower extremity deformities Nearly total neonatal alopecia No clinical abnormalities |
Hypocalcemia Hypophosphatemia Very high ALP and PTH Low 25(OH)D2 Normal 1,25(OH)2D3 Normal serum Ca and P levels at 4 months, but hypocalcemia, high PTH and ALP at 6 months |
Oral elemental Ca 2–4 g/d + calcitriol 2–4 μg/d + phosphorus 1 g/d iv calcium 150 mg/kg/d Cinacalcet 0.25–0.40 mg/kg/d + oral calcium 4 g/d + calcitriol 6 μg/d Calcitriol 2–4 μg/d + intermittent oral and iv calcium Cinacalcet 0.25 mg/kg/d + oral elemental Ca 1 g/d + calcitriol 2 μg/d |
14 weeks 4 months 5 months 2 months 5 months |
No improvement Clinical and radiological improvement, but recurrence when therapy off Biological and radiological healing Temporary metabolic and radiological improvement Biological and radiological healing |
(3) |
| Two compound heterozygous mutations in the ligand-binding site of VDR
heterogeneous missense mutation of Arg274 (Arg274His) in exon 9 heterogeneous missense mutation of Arg73 (Arg73Glu) in exon 5 |
19-month-old female Non consanguineous parents of Hispanic origin Child's country of origin-Unites States of America |
Poor growth | Hypocalcemia Normal phosphatemia Very high ALP and PTH Low 25(OH)D2 Very high 1,25(OH)2D3 |
Ergocalciferol 4,000 IU/d + oral and iv calcium Calcitriol 8 μg/d |
2 months 6 months |
Fluctuating calcemia Biological and radiological healing |
(4) |
| Homozygous p.K45E mutation located in the DNA-binding domain of the VDR gene (5/8) Homozygous p.T415R mutation located in the ligand-binding domain in the VDR gene (1/8) |
8 toddlers (age between 8 and 36 months) Consanguineous parents from Tunisia (7/8) Children's country of origin-Tunisia |
Alopecia (7/8) Growth retardation (7/8) Skeletal abnormalities (7/8) Motor developmental delay (5/8) |
Hypocalcemia (8/8) Hypophosphatemia (8/8) Very high ALP and PTH (8/8) High 1,25(OH)2D3 (8/8) Normal 25(OH)D2 (7/8) |
Alfacalcidol 12 −20 μg/d + oral calcium 2 g/d (8/8) Alfacalcidol 6 μg/d + iv calcium + oral calcium 1 g/d (6/8) |
6 months 2.6 years |
No clinical and laboratory improvement Clinical and radiological improvement |
(5) |
| Homozygous nonsense mutation p.Arg73-Ter, in the DNA-binding domain of the VDR gene and uniparental disomy of maternal chromosome 12 | 2-year-old girl Non-consanguineous parents Child's country of origin-Japan |
Partial alopecia Short stature Gait instability Lower extremity deformities |
Hypocalcemia Hypophosphatemia Very high ALP and PTH Normal 25(OH)D2 High 1,25(OH)2D3 |
Alfacalcidol 5 μg/d + oral calcium 60 mg/kg/d Oral calcium 250 mg/kg/d |
12 months 20 months |
No improvement Biological and radiological improvement |
(6) |
| Homozygous splice acceptor mutation (c.147–2A>T) in intron 2 of the VDR gene |
15-month-old boy Consanguineous parents from Pakistan Child's country of origin-United Kingdom |
Alopecia Growth failure Gross motor developmental delay |
Hypocalcemia Hypophosphatemia Very high ALP and PTH Low 25(OH)D2 Very high 1,25(OH)2D3 |
Ergocalciferol 6000 IU/d + elemental calcium po iv calcium |
3 months 8 months |
No improvement Biological and radiological healing |
(7) |
| Missense mutation in exon 2 in the DNA-binding domain of VDR | 13-month-old boy Child's country of origin-United States of America |
Partial alopecia Failure to thrive Rachitic deformities |
Hypocalcemia Hypophosphatemia Very high ALP and PTH Low 25(OH)D2 Very high 1,25(OH)2D3 |
Oral calcium + calcitriol iv calcium 450–600 mg/d Cinacalcet, 0.25–1 mg/kg/d |
6 months 6 months 19 months |
No improvement Biological and radiological improvement, but recurrence when therapy off Biological and radiological healing |
(8) |
| Skipped exon 8 in the VDR ligand-binding domain | 24-month-old girl Consanguineous parents from Mexico Child's country of origin-United States of America |
Partial neonatal alopecia Multiple fractures Generalized hypotonia with motor delay Respiratory events with acute respiratory distress |
Hypocalcemia Hypophosphatemia Very high ALP and PTH Low 25(OH)D2 Very high 1,25(OH)2D3 |
Ergocalciferol 4000 to 20,000 IU/d and then calcitriol 70–110 ng/kg/d + elemental calcium po + phosphorus iv calcium 30 to 147 mg/kg/d High-dose oral calcium |
4.5 months | No improvement Normal calcemia and PTH Radiographic signs of healing |
(9) |