Homocystinuria due to Cystathionine Beta-Synthase Deficiency

Homocystinuria due to cystathionine ß-synthase (CBS) deficiency is the most common inborn error of methionine metabolism, characterized by involvement of the eye (ectopia lentis and/or severe myopia), skeletal system (marfanoid habitus, osteoporosis, scoliosis, pectus excavatum, genu valgum), vascular system (premature atherosclerosis and thromboembolism), and central nervous system (developmental delay/mental retardation, seizures, psychiatric problems). Any or all of these systems may be involved. There is variable expressivity even among patients within the same family. Ectopia lentis may be the only presenting feature in some patients, other individuals can present with a thromboembolic event as an adult. About half of all CBS deficient patients respond to pharmacologic doses of pyridoxine (vitamin B6). Pyridoxine-responsiveness is constant within sibships. It has been estimated that newborn screening for elevated methionine levels detects only about one-third of patients.

Tests Available

Forms and Documents

Test Details

CBS
  • Confirmation of biochemical diagnosis
  • Carrier testing
  • Prenatal diagnosis in at risk pregnancies
  • Capillary Sequencing Reflex to Exon Array

Ordering

331
4-5 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81406x1
No
Yes
  • 270.45 Homocystinuria
* For price inquiries please email zebras@genedx.com

References

  1. Kraus et al., (1999) Hum Mutat 13:362-375
  2. Kruger et al., (2003) Hum Mutat 22:434-441
  3. Linnebank et al., (2004) Hum Mutat 24:352-353
  4. Urreizti et al., (2006) J Hum Genet 51:305-313
  5. Refsum et al., (2004) J Pediatr 144 :830-832

Forms and Documents

Test Details

ACTA2, ADAMTS2, ALDH18A1, ATP6V0A2, ATP7A, B3GALT6, B4GALT7, CBS, CHST14, COL11A1, COL11A2, COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL9A1, COL9A2, DSE, EFEMP2, ELN, FBLN5, FBN1, FBN2, FKBP14, FLNA, LTBP4, MAT2A, MED12, MFAP5, MYH11, MYLK, NOTCH1, PLOD1, PRDM5, PRKG1, PYCR1, RIN2, SKI, SLC2A10, SLC39A13, SMAD3, SMAD4, TGFB2, TGFB3, TGFBR1, TGFBR2, ZNF469
  • Molecular confirmation of a clinical diagnosis in symptomatic individuals
  • Risk assessment of asymptomatic family members of a proband diagnosed with a heritable connective tissue disorder
  • Genetic counseling and recurrence risk determination
  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

J555
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81410x1, 81411x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Murphy-Ryan M et al. (2010) Genet Med 12(6):344-54 (PMID: 20467323)
  2. Alazami AM et al. (2016) Hum Genet 135(5):525-40 (PMID: 27023906)
  3. Bradley TJ et al. (2016) Can J Cardiol 32(1):86-99 (PMID: 26724513)
  4. Weerakkody et al. (2016) Genet Med [Epub ahead of print] (PMID: 27011056)
  5. Ziganshin et al. (2015) Ann Thorac Surg 100(5):1604-11 (PMID: 26188975)
  6. Milewicz DM, Regalado E. Thoracic Aortic Aneurysms and Aortic Dissections. 2003 Feb 13 [Updated 2012 Jan 12]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.
  7. Guo et al. (2015) Am J Hum Genet 96 (1):170-7 (PMID: 25557781)
  8. Barbier et al. (2014) Am J Hum Genet 95(6):736-43 (PMID: 25434006)
  9. Callewaert B et al. Arterial Tortuosity Syndrome. 2014 Nov 13. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.
  10. Loeys BL, Dietz HC. Loeys-Dietz Syndrome. 2008 Feb 28 [updated 2013 Jul 11]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.
  11. Pepin MG et al. Vascular Ehlers-Danlos Syndrome. 1999 Sep 2 [updated 2015 Nov 19] In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.
  12. Merla et al. (2012) Circ Cardiovasc Genet 5(6):692-6 (PMID: 23250899)
  13. Beighton P et al. (1998) Am J Med Genet 77(1):31-7 (PMID: 9557891)
  14. Doyle AJ et al. (2012) Nat Genet 44(11):1249-54 (PMID: 23023332)
  15. Sadiq MA, Vanderveen D. (2013) Semin Ophthalmol 28(5-6):313-20 (PMID: 24138040)
  16. Guo et al. (2007) Nat Genet 39(12):1488-93 (PMID: 17994018)
  17. Al-Hussain H et al. (2004) Am J Med Genet 124A(1):28-34 (PMID: 14679583)
  18. Acke FR et al. (2012) Orphanet J Rare Dis 7:84 (PMID: 23110709)
  19. Baumann et al. (2012) Am J Hum Genet 90(2):201-16 (PMID: 22265013)
  20. Chen MH, Walsh CA. FLNA-Related Periventricular Nodular Heterotopia. 2002 Oct 8 [updated 2015 Sep 17]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.
  21. Greally MT. Shprintzen-Goldberg Syndrome. 2006 Jan 13 [updated 2013 Jun 13]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.
  22. Picker JD, Levy HL. Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency. 2004 Jan 15 [updated 2014 Nov 13]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-201

CREATE A CUSTOM PANEL

Test Details

  • Confirmation of clinical diagnosis in symptomatic patients
  • Genetic counseling and risk assessment of asymptomatic family members of a proband with a hereditary cardiovascular condition

Customizable Cardiology Panel

  • Next-Gen Sequencing
  • Exon Array CGH

Ordering

J779
4 weeks

Billing

Varies by gene
No
Yes
* For price inquiries please email zebras@genedx.com

Forms and Documents

CREATE A CUSTOM PANEL

Test Details

  • Molecular confirmation of a clinical diagnosis in symptomatic individuals
  • Risk assessment of asymptomatic family members of a proband diagnosed with a heritable connective tissue disorder
  • Genetic counseling and recurrence risk determination

Customizable Cardiology Panel

  • ExonArray CGH
  • Next-Gen Sequencing

Ordering

J555C
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81410x1, 81411x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Murphy-Ryan M et al. (2010) Genet Med 12(6):344-54 (PMID: 20467323)
  2. Alazami AM et al. (2016) Hum Genet 135(5):525-40 (PMID: 27023906)
  3. Bradley TJ et al. (2016) Can J Cardiol 32(1):86-99 (PMID: 26724513)
  4. Weerakkody et al. (2016) Genet Med [Epub ahead of print] (PMID: 27011056)
  5. Ziganshin et al. (2015) Ann Thorac Surg 100(5):1604-11 (PMID: 26188975)
  6. Milewicz DM, Regalado E. Thoracic Aortic Aneurysms and Aortic Dissections. 2003 Feb 13 [Updated 2012 Jan 12]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.
  7. Guo et al. (2015) Am J Hum Genet 96 (1):170-7 (PMID: 25557781)
  8. Barbier et al. (2014) Am J Hum Genet 95(6):736-43 (PMID: 25434006)
  9. Callewaert B et al. Arterial Tortuosity Syndrome. 2014 Nov 13. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.
  10. Loeys BL, Dietz HC. Loeys-Dietz Syndrome. 2008 Feb 28 [updated 2013 Jul 11]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.
  11. Pepin MG et al. Vascular Ehlers-Danlos Syndrome. 1999 Sep 2 [updated 2015 Nov 19] In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.
  12. Merla et al. (2012) Circ Cardiovasc Genet 5(6):692-6 (PMID: 23250899)
  13. Beighton P et al. (1998) Am J Med Genet 77(1):31-7 (PMID: 9557891)
  14. Doyle AJ et al. (2012) Nat Genet 44(11):1249-54 (PMID: 23023332)
  15. Sadiq MA, Vanderveen D. (2013) Semin Ophthalmol 28(5-6):313-20 (PMID: 24138040)
  16. Guo et al. (2007) Nat Genet 39(12):1488-93 (PMID: 17994018)
  17. Al-Hussain H et al. (2004) Am J Med Genet 124A(1):28-34 (PMID: 14679583)
  18. Acke FR et al. (2012) Orphanet J Rare Dis 7:84 (PMID: 23110709)
  19. Baumann et al. (2012) Am J Hum Genet 90(2):201-16 (PMID: 22265013)
  20. Chen MH, Walsh CA. FLNA-Related Periventricular Nodular Heterotopia. 2002 Oct 8 [updated 2015 Sep 17]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.
  21. Greally MT. Shprintzen-Goldberg Syndrome. 2006 Jan 13 [updated 2013 Jun 13]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.
  22. Picker JD, Levy HL. Homocystinuria Caused by Cystathionine Beta-Synthase Deficiency. 2004 Jan 15 [updated 2014 Nov 13]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-201