Ann Pediatr Endocrinol Metab.  2019 Jun;24(2):137-141. 10.6065/apem.2019.24.2.137.

A case of vitamin D hydroxylation-deficient rickets type 1A caused by 2 novel pathogenic variants in CYP27B1 gene

• Kim YM
• Jang YY
• Jeong JE
• Park HJ
• Jang JH
• Kim JK

• KMID: 2452092
• DOI: http://doi.org/10.6065/apem.2019.24.2.137

Abstract

Vitamin D hydroxylation-deficient rickets type 1A (VDDR1A, OMIM 264700) is a rare autosomal recessive inherited disorder. Pathogenic variants in the CYP27B1 gene lead to loss of 1α-hydroxylase activity. We report the case of a 22-month-old toddler who presented with growth retardation and delayed development. The patient exhibited the typical laboratory findings of VDDR1A, including hypocalcemia (calcium: 5.2 mg/dL), elevated serum level of alkaline phosphatase (2,600 U/L), elevated serum level of intact-parathyroid hormone (238 pg/mL), low 1,25(OH)₂D₃ level (11.2 pg/mL), and normal 25(OH)D₃ level (40.7 ng/mL). His height and weight were 76.5 cm and 9.5 kg, respectively (both <3rd percentile). The Bayley Scales of Infant and Toddler Development II indicated significantly delayed development (mental development index <50, psychomotor development index <50). The patient was a compound heterozygous for two novel pathogenic variants in the CYP27B1 gene: c.57_69del (p.Glu20Profs*2) and c.171dupG (p.Leu58Alafs*275), inherited from his mother and father, respectively. The patient showed remarkable improvement after treatment with calcitriol and calcium carbonate.

Keyword

Vitamin D hydroxylation-deficient rickets type1A; CYP27B1; Hypocalcemia

MeSH Terms

25-Hydroxyvitamin D3 1-alpha-Hydroxylase*
Alkaline Phosphatase
Calcitriol
Calcium Carbonate
Databases, Genetic
Fathers
Humans
Hypocalcemia
Infant
Mothers
Rickets*
Vitamin D*
Vitamins*
Weights and Measures
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Alkaline Phosphatase
Calcitriol
Calcium Carbonate
Vitamin D
Vitamins

Figure

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  Fig. 1. Radiological findings. Simple radiography shows fraying and cupping of the metaphyseal regions of the radius and ulnar (A), tibia and fibula (B). R, right; L, left.

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  Fig. 2. Genetic analysis of CYP27B1. (A) The sequencing chromatogram shows a heterozygous c.57_69del variant in the forward direction. The variant of the proband is inherited from the mother. (B) The chromatogram shows a heterozygous c.171dupG variant in the reverse direction. The variant of the proband is inherited from the father.

Reference

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