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LETTER TO EDITOR
Year : 2014  |  Volume : 62  |  Issue : 4  |  Page : 457-459

Cervical spinal cord compression caused by X-linked hypophosphatemic rickets with a novel PHEX mutation


1 Department of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
2 Department of Stomatology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China

Date of Web Publication19-Sep-2014

Correspondence Address:
Fei Xie
Department of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou
China
Fei Xie
Department of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou
China
Zhi-dong Cen
Department of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou
China
Zhi-dong Cen
Department of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.141271

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How to cite this article:
Xie F, Cen Zd, Chen Ll, Luo W, Xie F, Cen Zd, Chen Ll, Luo W. Cervical spinal cord compression caused by X-linked hypophosphatemic rickets with a novel PHEX mutation. Neurol India 2014;62:457-9

How to cite this URL:
Xie F, Cen Zd, Chen Ll, Luo W, Xie F, Cen Zd, Chen Ll, Luo W. Cervical spinal cord compression caused by X-linked hypophosphatemic rickets with a novel PHEX mutation. Neurol India [serial online] 2014 [cited 2020 Oct 31];62:457-9. Available from: https://www.neurologyindia.com/text.asp?2014/62/4/457/141271


Sir,

X-linked hypophosphatemic rickets (XLH) is an uncommon inherited phosphate-wasting disorder and is caused by the mutations in the PHEX gene. The typical features of XLH include rickets, short stature, bone pain, tooth abscesses and lower extremity deformities. [1],[2] In addition to these features, calcification of entheses (tendons, ligaments, and joint capsules) is common among these patients. [3] Spinal cord compression caused by ossification of spinal ligaments, especially the ossification of the posterior longitudinal ligament (OPLL), in XLH patients is rarely reported. Here, we report the first Chinese patient of XLH with cervical spinal cord compression caused by a novel PHEX mutation.

A 42-year-old Chinese woman presented with lower limb weakness and severe bone pain. She became wheelchair bound at the age of 38 years. Physical examination revealed short stature, bowing of legs [Figure 1]a, and loss all teeth [Figure 1]b. Neurologic examination revealed spastic paraplegia in the lower limbs (motor power 1/5) with sensory loss below the neck and mute plantar response. Magnetic resonance imaging (MRI) of cervical spine [Figure 1]c, done 5 years before revealed protrusion of cervical disc at C5-C6 and OPLL with significant cord compression. However, computed tomography of the cervical spine could not be done as the patients refused to the investigation. Laboratory investigations at the time of presentation revealed low serum phosphate 0.62 mmol/L (normal: 0.97-1.62 mmol/L), normal serum calcium 2.37 mmol/L (normal: 2.05-2.60 mmol/L), elevated alkaline phosphatase 218 U/L (normal: 30-140 U/L), elevated serum parathyroid hormone 81.49 pg/ml (normal: 15.00-65.00 pg/ml), normal 25-hydroxy vitamin 48.8 pmol/L (normal, 35-150 pmol/L). These findings supported the clinical diagnosis of XLH. Family pedigree showed five other living affected members [Figure 1]d. However, none of them has neurological deficits.
Figure 1: (a) The proband has been paralyzed to wheelchair-bound and her lower limbs were apparently bowing. (b) The proband lost almost all of her teeth. (c) T2-weighted, sagittal magnetic resonance imaging scan of the cervical spine, shows protrusion of cervical intervetebral disc at C5/C6 and the corresponding dural sac edge is signifi cntly compressed of the proband. Spinal canal stenosis at C4-C6 could be seen and may attribute to ossifi cation of the posterior longitudinal ligament (OPLL). (d) The pedigree of the XLH family

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Genetic screening was done after written informed consent. Sanger sequencing of PHEX gene identified a novel missense mutation c. 1643 T > C, p.Ile548Thr in exon 15 [Figure 2]a. The mutation was not recorded by the HGMD (http://www.hgmd.cf.ac.uk) or PHEX mutation database (http://www.phexdb.mcgill.ca). The mutation was co-segregated in the family and was absent in 100 matched chromosomes.

The mutation resulted in the substitution of highly conserved PHEX amino acids in different 24 species [Figure 2]b and was predicted to be probably damaging by PolyPhen analysis software. All of these suggested that this mutation was the causative mutation in this family.
Figure 2: Mutational analysis and evolutionary conservation of the residues p.548. (a) A missense mutation, c.1643T>C in exon 15 of the PHEX gene, was found. (b) The residue (p.548), which is marked in the figure, is highly conserved

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  Acknowledgment Top


This work was supported by the National Natural Science Foundation of China (Proj. No. 81371266 and 30973221) and the Program for Zhejiang Leading Team of Science and Technology Innovation (Proj. No. 2010R50049-04).

 
  References Top

1.Econs MJ, McEnery PT. Autosomal dominant hypophosphatemic rickets/osteomalacia: Clinical characterization of a novel renal phosphate-wasting disorder. J Clin Endocrinol Metab 1997;82:674-81.  Back to cited text no. 1
    
2.Gaucher C, Walrant-Debray O, Nguyen TM, Esterle L, Garabedian M, Jehan F. PHEX analysis in 118 pedigrees reveals new genetic clues in hypophosphatemic rickets. Hum Genet 2009;125:401-11.  Back to cited text no. 2
    
3.Polisson RP, Martinez S, Khoury M, Harrell RM, Lyles KW, Friedman N, et al. Calcification of entheses associated with X-linked hypophosphatemic osteomalacia. N Engl J Med 1985;313:1-6.  Back to cited text no. 3
    


    Figures

  [Figure 1], [Figure 2]

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