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Review
. 2022 Jul 29:13:911672.
doi: 10.3389/fendo.2022.911672. eCollection 2022.

Case Report and Review of Literature: Autosomal Recessive Hypophosphatemic Rickets Type 2 Caused by a Pathogenic Variant in ENPP1 Gene

Yunsoo Choe  1 , Choong Ho Shin  1 , Young Ah Lee  1 , Man Jin Kim  2 , Yun Jeong Lee  1
Affiliations
Review

Case Report and Review of Literature: Autosomal Recessive Hypophosphatemic Rickets Type 2 Caused by a Pathogenic Variant in ENPP1 Gene

Yunsoo Choe et al. Front Endocrinol (Lausanne). .

Abstract

Autosomal recessive hypophosphatemic rickets type 2 (ARHR2) is a rare form of hereditary rickets, which is characterized by defective bone mineralization and renal phosphate wasting due to a loss-of-function variant in the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene. Although pathogenic variant of ENPP1 has been known to manifest other phenotypes including arterial calcification, hearing loss, ossification of posterior longitudinal ligament, or pseudoxanthoma elasticum, there have been few reports including systematic examination in individuals diagnosed with ARHR2 to date. Herein, we report a case of ARHR2 with a bi-allelic pathogenic variant of ENPP1, in which the patient presented with gait abnormalities with severe genu varum at 26 months of age. Targeted gene panel sequencing was performed to investigate the genetic cause of rickets, and a homozygous nonsense variant in ENPP1, c.783C>G (p.Tyr261*), was identified. The patient was treated with oral phosphate and active vitamin D supplements and underwent corrective osteotomy for varus deformity. His phenotype was limited to rickets. A periodic systematic evaluation is needed to identify any comorbidities in ARHR2 patients since ENPP1 variants may present phenotypes other than rickets and symptoms may evolve or change over time.

Keywords: autosomal recessive hypophosphatemic rickets; case report; child; ectonucleotide pyrophosphatase phosphodiesterase 1; rickets.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Clinical photograph and radiological findings of the patient. (A) Photograph of the patient’s bowed legs at 24 months of age. (B) Plain radiograph of the lower extremities showing bilateral metaphyseal flaring of the distal femur and tibia, associated with varus deformity, at 30 months of age.
Figure 2
Figure 2
Genetic analysis of ENPP1 gene and pedigree of the family. (A) Genomic DNA sequences of the patient and his parents exhibiting either homozygous or heterozygous c.783C>G (p.Tyr261*) variant in the ENPP1 gene. (B) Pedigree of the family. The variants identified in the ENPP1 gene are indicated below each individual. The black arrow indicates the proband.
See this image and copyright information in PMC

References

    1. Lorenz-Depiereux B, Schnabel D, Tiosano D, Häusler G, Strom TM. Loss-Of-Function Enpp1 Mutations Cause Both Generalized Arterial Calcification of Infancy and Autosomal-Recessive Hypophosphatemic Rickets. Am J Hum Genet (2010) 86(2):267–72. doi: 10.1016/j.ajhg.2010.01.006 - DOI - PMC - PubMed
    1. Höppner J, Kornak U, Sinningen K, Rutsch F, Oheim R, Grasemann C. Autosomal Recessive Hypophosphatemic Rickets Type 2 (Arhr2) Due to Enpp1-Deficiency. Bone (2021) 153:116111. doi: 10.1016/j.bone.2021.116111 - DOI - PubMed
    1. Rutsch F, Ruf N, Vaingankar S, Toliat MR, Suk A, Höhne W, et al. Mutations in Enpp1 Are Associated With 'Idiopathic' Infantile Arterial Calcification. Nat Genet (2003) 34(4):379–81. doi: 10.1038/ng1221 - DOI - PubMed
    1. Saito T, Shimizu Y, Hori M, Taguchi M, Igarashi T, Fukumoto S, et al. A Patient With Hypophosphatemic Rickets and Ossification of Posterior Longitudinal Ligament Caused by a Novel Homozygous Mutation in Enpp1 Gene. Bone (2011) 49(4):913–6. doi: 10.1016/j.bone.2011.06.029 - DOI - PubMed
    1. Nitschke Y, Baujat G, Botschen U, Wittkampf T, du Moulin M, Stella J, et al. Generalized Arterial Calcification of Infancy and Pseudoxanthoma Elasticum Can Be Caused by Mutations in Either Enpp1 or Abcc6. Am J Hum Genet (2012) 90(1):25–39. doi: 10.1016/j.ajhg.2011.11.020 - DOI - PMC - PubMed

Supplementary concepts