Clinical spectrum and diagnostic challenges of vitamin D dependent rickets type 1A (VDDR1A) caused by CYP27B1 mutation in resource limited countries

J Pediatr Endocrinol Metab. 2022 Dec 19;36(2):152-157. doi: 10.1515/jpem-2022-0550. Print 2023 Feb 23.


Objectives: Vitamin D dependent rickets type 1A (VDDR1A) is a rare autosomal recessive condition due to inactivating mutation of CYP27B1. It mimics clinically, biochemically and rediologically to nutritional and hypophosphatemic rickets. In developing countries like Pakistan, VDDR1A is often misdiagnosed as nutritional rickets or hypophosphatemic rickets due lack of free access to 1,25 (OH) 2 D level and genetic testing. This study was aimed to determine the clinical spectrum and diagnostic challenges of VDDR1A due to CYP27B1 mutation in developing countries.

Methods: Retrospective review of all cases of VDDR1A due to CYP27B1 mutation over a period of two years presenting in the Pediatric Endocrine clinic of Hameed Latif Hospital, Lahore, Pakistan.

Results: Six cases of VDDR1A (4 males) were identified. Mean age of clinical manifestation was 14 (9-24) months. Mean age of presentation to endocrine department was 5.5 (1.5-11.8) years. Growth failure and bony deformities were the most common presentation (n=6), followed by repeated diarrheas and abdominal distension (n=3) and recurrent fractures (n=1). All cases shared same biochemical profile of low/normal calcium, hypophosphatemia, raised alkaline phosphatase, raised PTH, normal/high 25(OH)D and tubular reabsorption of phosphate (TRP) <85%. Patients treated with calcitriol showed rapid healing as compared to those treated with 1-alfacalcidol.

Conclusions: We should have a high index of suspicion of VDDR1A in rickets not responding to cholecalciferol therapy.

Keywords: CYP27B1; VDDR1A; vitamin D dependent type 1A rickets.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • Calcitriol / therapeutic use
  • Child
  • Child, Preschool
  • Familial Hypophosphatemic Rickets* / diagnosis
  • Familial Hypophosphatemic Rickets* / drug therapy
  • Familial Hypophosphatemic Rickets* / genetics
  • Female
  • Humans
  • Infant
  • Male
  • Mutation
  • Rickets* / diagnosis
  • Rickets* / drug therapy
  • Rickets* / genetics
  • Rickets, Hypophosphatemic* / drug therapy
  • Vitamin D / therapeutic use


  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Calcitriol
  • CYP27B1 protein, human
  • Vitamin D

Supplementary concepts

  • Vitamin D Hydroxylation-Deficient Rickets, Type 1A