Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
권호 표지
DOI QR코드

DOI QR Code

Dopa-responsive dystonia with additional unusual clinical features: A case report confirmed by molecular genetics

  • Lee, Woong-Woo (Department of Neurology, Nowon Eulji Medical Center, Eulji University) ;
  • Choi, Jong-Moon (Department of Laboratory Medicine, GC Genome) ;
  • Lee, Cha Gon (Department of Pediatrics, Nowon Eulji Medical Center, Eulji University)
  • Received : 2019.12.23
  • Accepted : 2020.02.01
  • Published : 2020.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

The term dopa-responsive dystonia (DRD) is used to describe a group of neurometabolic disorders, which are characterized by dystonia, and are typically associated with diurnal fluctuations and respond to levodopa treatment. Autosomal dominant DRD (DYT5a, MIM# 128230) is caused by a heterozygous mutation in the GTP cyclohydrolase 1 (GCH1) gene (MIM# 600225). GCH1 encodes an enzyme, which is involved in the biosynthesis of tetrahydrobiopterin, an essential co-factor for tyrosine hydroxylase. Herein, we report the case of a 16-year-old girl who was diagnosed with DYT5a. She exhibited additional unusual clinical features, including intellectual disability, depression, multiple skeletal anomalies, and short stature, which are not commonly observed in patients with DYT5a. The patient harbored a heterozygous missense variant, c.539A>C, p.Gln180Pro, in the GCH1 gene, which was identified by targeted gene panel analysis using next-generation sequencing.

Keywords

References

  1. Segawa M. Childhood basal ganglia disease with remarkable response to L-dopa, hereditary basal ganglia disease with marked diurnal fluctuation. Shinryo (Tokyo) 1971;24:667-72.
  2. Phukan J, Albanese A, Gasser T, Warner T. Primary dystonia and dystonia-plus syndromes: clinical characteristics, diagnosis, and pathogenesis. Lancet Neurol 2011;10:1074-85. https://doi.org/10.1016/S1474-4422(11)70232-0
  3. Segawa M. Autosomal dominant GTP cyclohydrolase I (AD GCH 1) deficiency (Segawa disease, dystonia 5; DYT 5). Chang Gung Med J 2009;32:1-11.
  4. Clot F, Grabli D, Cazeneuve C, Roze E, Castelnau P, Chabrol B, et al. Exhaustive analysis of BH4 and dopamine biosynthesis genes in patients with Dopa-responsive dystonia. Brain 2009;132(Pt 7):1753-63. https://doi.org/10.1093/brain/awp084
  5. Tassin J, Durr A, Bonnet AM, Gil R, Vidailhet M, Lucking CB, et al. Levodopa-responsive dystonia. GTP cyclohydrolase I or parkin mutations? Brain 2000;123(Pt 6):1112-21. https://doi.org/10.1093/brain/123.6.1112
  6. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405-24. https://doi.org/10.1038/gim.2015.30
  7. Lee WW, Jeon BS. Clinical spectrum of dopa-responsive dystonia and related disorders. Curr Neurol Neurosci Rep 2014;14:461. https://doi.org/10.1007/s11910-014-0461-9
  8. Sunga MA, Rosales RL. Mental dysfunctions in dystonia-plus syndromes. J Parkinsons Dis 2014;4:161-7. https://doi.org/10.3233/JPD-130283
  9. Tsirikos AI, Carr LJ, Noordeen HH. Variability of clinical expression and evolution of spinal deformity in a family with late detection of doparesponsive dystonia. Dev Med Child Neurol 2004;46:128-37. https://doi.org/10.1111/j.1469-8749.2004.tb00462.x
  10. Lopez-Laso E, Sanchez-Raya A, Moriana JA, Martinez-Gual E, Camino-Leon R, Mateos-Gonzalez ME, et al. Neuropsychiatric symptoms and intelligence quotient in autosomal dominant Segawa disease. J Neurol 2011;258:2155-62. https://doi.org/10.1007/s00415-011-6079-9
  11. Van Hove JL, Steyaert J, Matthijs G, Legius E, Theys P, Wevers R, et al. Expanded motor and psychiatric phenotype in autosomal dominant Segawa syndrome due to GTP cyclohydrolase deficiency. J Neurol Neurosurg Psychiatry 2006;77:18-23. https://doi.org/10.1136/jnnp.2004.051664
  12. Hahn H, Trant MR, Brownstein MJ, Harper RA, Milstien S, Butler IJ. Neurologic and psychiatric manifestations in a family with a mutation in exon 2 of the guanosine triphosphate-cyclohydrolase gene. Arch Neurol 2001;58:749-55. https://doi.org/10.1001/archneur.58.5.749
  13. Furukawa Y, Kish SJ, Bebin EM, Jacobson RD, Fryburg JS, Wilson WG, et al. Dystonia with motor delay in compound heterozygotes for GTP-cyclohydrolase I gene mutations. Ann Neurol 1998;44:10-6. https://doi.org/10.1002/ana.410440107
  14. Kim R, Jeon B, Lee WW. A systematic review of treatment outcome in patients with dopa-responsive dystonia (DRD) and DRD-plus. Mov Disord Clin Pract 2016;3:435-42. https://doi.org/10.1002/mdc3.12361
  15. Sadahiro R, Suzuki A, Matsumoto Y, Shibuya N, Enokido M, Kamata M, et al. Functional polymorphism of the GTP cyclohydrolase 1 gene affects the personality trait of novelty seeking in healthy subjects. Neurosci Lett 2011;503:220-3. https://doi.org/10.1016/j.neulet.2011.08.040
  16. Bhandutia AK, Nangunoori R, Whiting DM, Sangimino MJ. Scoliosis secondary to dystonia: a case report and review of the literature. JBJS Case Connect 2017;7:e47. https://doi.org/10.2106/JBJS.CC.16.00193