Tyrosine Hydroxylase Deficiency

Tyrosine hydroxylase (TH) deficiency is a rare autosomal recessive movement disorder with onset typically within the first years of life. It is associated with phenotypic variability that ranges from dopa-responsive dystonia (DRD) to dopa-responsive infantile parkinsonism to infantile progressive encephalopathy that is not dopa-responsive. Additional features may include hypotonia, hypokinesia, oculogyric crises and ptosis, and autonomic signs (temperature instability, hypoglycemia). A diurnal fluctuation of symptoms may be evident. Carriers are usually asymptomatic but some have been reported with restless leg symptoms and exerciseinduced stiffness. TH deficiency is typically characterized by decreased levels of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) with normal levels of 5-hydroxyindoleacetic acid (5-HIAA) and a decreased HVA/5-HIAA ratio in cerebrospinal fluid. There is no specific biochemical test for this disorder. TH deficiency is caused by mutations in the TH gene on chromosome 11p15.5. Definitive diagnosis requires the identification of mutations in the TH gene. The phenotype associated with TH deficient doparesponsive dystonia may significantly overlap with DRD caused by GCH1 gene mutations, but may also be more complex (DRD-plus syndrome). Molecular testing of the TH gene should be undertaken in patients with a complex DRD presentation, and in patients negative for a GCH1 gene mutation with simple DRD. Mutation analysis of the GCH1 gene is available at GeneDx

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Test Details

TH
  • Confirmation of a clinical diagnosis
  • Identification of at-risk family members
  • Capillary Sequencing

Ordering

359
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs

Billing

81406x1
No
Yes
  • 348.3 Encephalopathy, not elsewhere classified
  • 780.6 Fever and other physiologic disturbances of temperature regulation
  • 251.2 Hypoglycemia, unspecified Hypoglycemia: NOS reactive spontaneous
  • 374.3 Ptosis of eyelid
  • 781 Symptoms involving nervous and musculoskeletal systems Excludes: depression NOS (311) disorders specifically relating to: back (724.0-724.9) hearing (388.0-389.9) joint (718.0-719.9) limb (729.0-729.9) neck (723.0-723.9) vision (368.0-369.9) pain in limb (729.5)
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References

  1. HGMD Professional 2010.3
  2. Willemsen et al., (2010) Brain 133:1810-1822
  3. Pons R et al., (2010) Mov Disord 25(8): 1086-90
  4. Zafeiriou et al., (2009) Mol Genet Metab 97:18-20
  5. Clot et al., (2009) Brain 132: 1753- 1763
  6. Swoboda (2008) TH Deficiency http://www.genetests.org
  7. Verbeek et al., (2007) Ann Neurol 62:422-426
  8. Ribases et al., (2007) Mol Genet Metab 92:274-277
  9. Schiller et al., (2004) Neurology 63:1524-1526
  10. Furukawa et al., (2001) Neurology 56:260-263
  11. Janssen et al., (2000) Ann Hum Genet 64:375-382
  12. Wevers et al., (1999) J Inher Metab Dis 22:364- 373
  13. Van den Heuvel et al., (1998) Hum Genet 102:644-6