Dopa-Responsive Dystonia

Dopa-Responsive Dystonia (DRD) is a treatable neurological condition which can present with a variety of symptoms ranging from dystonia, spastic paraparesis, and proximal weakness to Parkinsonism. A family history of dystonia or Parkinson disease is common. At least 50% of patients have diurnal fluctuation with marked progression of their symptoms toward the end of the day and relief after sleep. The clinical features in patients with mutations in the GCH1 gene are characterized by pure dystonia with onset in the lower limbs and dramatic improvement with small doses of L-Dopa. Dystonia generally starts in the first decade, but later onset is also observed. In contrast to patients with Juvenile Parkinson’s disease, these patients do not usually develop levodopa-induced fluctuations or dyskinesia. There are at least three causative genes for DRD including genes that encode GTP cyclohydrolase 1 (GCH1), tyrosine hydroxylase (TH), and sepiapterin reductase (SPR). Females predominate among clinically affected individuals. Genetic testing should be guided by the analysis of cerebrospinal fluid levels of biopterin and neopterin, which are low in GTPCH1-deficient DRD. Prevalence of DRD in Japan and England is estimated at 1 in 2 million. No increased prevalence has been reported in any ethnic group.

Tests Available

Forms and Documents

Test Details

GCH1
  • Confirmation of a clinical diagnosis
  • Selection of appropriate treatment
  • Identification of at-risk family members
  • Capillary Sequencing

Ordering

230
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81405x1
Yes
Yes
  • 270.1 Phenylketonuria [PKU], Hyperphenylalaninemia
  • 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)
* For price inquiries please email zebras@genedx.com

References

  1. Furukawa Y, (2009) Gene Reviews GTPCH1-Deficient DRD
  2. Clot F et Al., (2009) Brain 132: 1753-1763
  3. Thony B and Blau N, (2006) Hum Mutat 27:870- 878
  4. Zirn B et Al., (2008) J Neurol Neurosurg Psych 79:183-186
  5. Hagenah et Al., (2005) Neurology 64:908-911
  6. Muller U et Al., (2002) J Neural Transm 109:321-328
  7. Furukawa Y, (2004) Adv Neurol 94:127-138
  8. Furukawa Y et Al., (1998) Neurology 50:1015-20
  9. Furukawa Y et Al., (1998) Ann Neurol 44: 10-16
  10. Ichinose H et Al., (1994) Nat Genet 8:236-242
  11. Muller Y et Al., (1998) Neurogenetics 1:165-177
  12. Bandmann O et Al., (1996) Hum Molec Genet 5:403-406

Forms and Documents

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)
* For price inquiries please email zebras@genedx.com

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

Forms and Documents

Test Details

GCH1
  • Confirmation of a clinical diagnosis
  • Selection of appropriate treatment
  • Identification of at-risk family members
  • Capillary Sequencing
  • Exon Array CGH

Ordering

527
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81405x1, 81479x1
No
Yes
  • 270.1 Phenylketonuria [PKU], Hyperphenylalaninemia
  • 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)
* For price inquiries please email zebras@genedx.com

References

  1. Muller Y et Al., (1998) Neurogenetics 1:165-177.
  2. Ichinose H et Al., (1994) Nat Genet 8:236-242.
  3. Bandmann O et Al., (1996) Hum Molec Genet 5:403-406.
  4. Furukawa Y et Al., (1998) Ann Neurol 44: 10-16.
  5. Furukawa Y et Al., (1998) Neurology 50:1015-20.
  6. Muller U et Al., (2002) J Neural Transm 109:321-328
  7. Furukawa Y, (2004) Adv Neurol 94:127-138.
  8. Hagenah et Al., (2005) Neurology 64:908-911.
  9. Thony B and Blau N, (2006) Hum Mutat 27:870- 878.
  10. Zirn B et Al., (2008) J Neurol Neurosurg Psych 79:183-186.
  11. Clot F et Al., (2009) Brain 132: 1753-1763.
  12. Furukawa Y, (2009) Gene Reviews GTPCH1-Deficient DRD.

Forms and Documents

Test Details

ADAR, ADCY5, AFG3L2, ANO3, APOE, APTX, ARSA, ATM, ATP13A2, ATP1A3, ATP6AP2, ATP7B, C10orf2, C19orf12, CACNA1A, COASY, CP, CYP27A1, DCAF17, DLAT, DNAJC5, DNAJC6, FA2H, FBXO7, FTL, GBA, GCDH, GCH1, GLRA1, GNAL, KCNMA1, KMT2B, LRRK2, MARS2, MCOLN1, MRE11A, NKX2-1, NPC1, NPC2, PANK2, PARK2, PARK7, PDGFB, PINK1, PLA2G6, PNKD, PNKP, POLG, POLR3B, PRKRA, PRRT2, SCP2, SGCE, SLC16A2, SLC20A2, SLC2A1, SLC30A10, SLC6A3, SMPD1, SNCA, SPR, SYNJ1, TH, THAP1, TIMM8A, TOR1A, TOR1AIP1, TPK1, TRAPPC11, TUBB4A, VPS13A, VPS35, WDR45, XPR1
  • Molecular confirmation of a clinical diagnosis
  • Identification of at-risk family members
  • Assist with treatment/ management decisions
  • Recurrence risk assessment
  • Prenatal diagnosis for known familial pathogenic variant(s) in at-risk pregnancies IF appropriate
  • Next-Gen Sequencing
  • Deletion/Duplication Analysis
  • Capillary Sequencing

Ordering

T402
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81404x4, 81405x2, 81406x2, 81407x1, 81408x1
No
Yes
* For price inquiries please email zebras@genedx.com

Forms and Documents

Test Details

ADAR, ADCY5, AFG3L2, ANO3, APTX, ARSA, ATM, ATP13A2, ATP1A3, ATP7B, CACNA1A, COASY, CYP27A1, DCAF17, DLAT, FA2H, FTL, GCDH, GCH1, GLRA1, GNAL, KMT2B, MARS2, MRE11A, NKX2-1, NPC1, NPC2, PANK2, PDGFB, PLA2G6, PNKD, PNKP, POLR3B, PRKRA, PRRT2, SCP2, SGCE, SLC16A2, SLC20A2, SLC2A1, SLC30A10, SPR, SYNJ1, TH, THAP1, TIMM8A, TOR1A, TPK1, TRAPPC11, TUBB4A, VPS13A, WDR45, XPR1
  • Molecular confirmation of a clinical diagnosis
  • Identification of at-risk family members
  • Assist with treatment/ management decisions
  • Recurrence risk assessment
  • Prenatal diagnosis for known familial pathogenic variant(s) in at-risk pregnancies IF appropriate
  • Next-Gen Sequencing
  • Deletion/Duplication Analysis

Ordering

T403
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81404x1, 81405x2, 81406x1
No
Yes
* For price inquiries please email zebras@genedx.com