Evaluation of Clinical Characteristics of Vitamin D Dependent Rickets Type 1 (VDDR-1) Patients and Importance of Early Diagnosis D Vitamini Bağımlı Raşitizm Tip 1 (VDDR-1) Hastalarının Klinik Özelliklerinin Değerlendirilmesi ve Erken Tanının Önemi
Guncel Pediatri, cilt.20, sa.3, ss.373-378, 2022 (ESCI, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 20 Sayı: 3
- Basım Tarihi: 2022
- Doi Numarası: 10.4274/jcp.2022.66564
- Dergi Adı: Guncel Pediatri
- Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus, Academic Search Premier, CAB Abstracts, CINAHL, EMBASE, Veterinary Science Database
- Sayfa Sayıları: ss.373-378
- Anahtar Kelimeler: CYP27B1, vitamin D-dependent rickets type 1A, hypocalcemia, hypophosphatemia
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Introduction: Vitamin D-dependent rickets type 1 (VDDR-1) is an autosomal recessive disorder caused by 1-α-hydroxylase enzyme deficiency. This rare disease occurs due to biallelic pathogenic variants in the CYP27B1 gene. We evaluated VDDR-1 patients retrospectively in terms of clinical and biochemical characteristics, treatment response, and genetic results. Materials and Methods: VDDR-1 cases with biallelic variants in CYP27B1 from 12 families were included. Demographic and clinical data were extracted from records. Following DNA isolation and standardized PCR, we performed next-generation sequencing with Miseq device. Data analysis was performed using IGV 2.3 software. Results: The cohort included 22 patients, 11 (50%) female and 11 male. Median age at diagnosis was 12 (7.75-18) months. Mean calcium, phosphorus, alkaline phosphatase (ALP) and vitamin D concentration was 7.6±0.98 mg/dL, 2.9±0.77 mg/dL, 1149±692 IU/L, 391±181 pg/mL, and 55±38 ng/mL, respectively at diagnosis The most common reasons for presentation were growth retardation, short stature, convulsions, and extremity deformity. The most common variant was the previously identified c.195 + 2T>G substitution, which was detected in 5 families. The second most common variant was another previously reported c.574A>G (p.Lys192Glu) variant, which was detected in 3 families. c.171delC (p.Leu.58Cfs*20), c.240delT (p.Phe80Leufs*79), and c.1166G>A(p.Arg389His) homozygous variants and c.1215_1215+2delinsCGA/c.1474C>T (p.Arg492Trp) compound heterozygous variant were detected in one family each. Conclusion: VDDR-1 should be considered in rickets patients not recovering with high-dose vitamin D therapy. Delayed diagnosis of VDDR-1 may lead to unnecessary orthopedic surgery in some cases. We are of the opinion that providing early diagnosis, treatment and genetic counseling will give reliable and important information to families.