Multiple Acyl-CoA Dehydrogenase Deficiency (MADD)

Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) or Glutaric Aciduria II (GAII) is an extremely rare disorder that can result from deficiency of the alpha or beta subunits of electron transfer flavoprotein or its dehydrgenase ETF:ubiqinone oxidoreductase (ETF-DH or ETF:QO). Defects in any of these genes may lead to a range of clinical phenotypes from mild to severe, depending upon the mutation. Three clinical phenotypes for GAII have been described. Type I presents as a life-threatening disorder during the neonatal period with tachypnea, dyspnea, profound acidosis, severe hypotonia and convulsions. Hepatomegaly, hypoketotic hypoglycaemia, hyperammonemia, sweaty-sock like odor and congenital anomalies including renal cystic dysplasia, heart abnormalities, central nervous system malformations, facial dysmorphism, rocker bottom feet, and abnormalities of the external genitalia may also be present. Type II presentation is similar to Type I without the congenital anomalies, while a Type III presentation occurs later with intermittent episodes of vomiting, hypoglycemia, and metabolic acidosis during infancy or episodic muscular weakness and pain during adulthood along with progressive myopathy. Recurrent panceatitis has also been reported with abdominal symptoms.

Tests Available

Forms and Documents

Test Details

ETFA
  • Diagnostic confirmation
  • Carrier testing
  • Prenatal diagnosis in at-risk pregnancies
  • Capillary Sequencing

Ordering

278
4-5 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 277.87 Disorders of mitochondrial metabolism, Kearns-Sayre syndrome, Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes (MELAS syndrome), Mitochondrial Neurogastrointestinal Encephalopathy syndrome (MNGIE), Myoclonus with Epilepsy and with Ragged Red Fibers (MERRF syndrome), Neuropathy, Ataxia and Retinitis Pigmentosa (NARP syndrome)
* For price inquiries please email zebras@genedx.com

References

  1. Wen et al., (2010) J Neurosurg Psychiatry 81:231-236.
  2. Yotsumoto et al., (2008) Mol Genet Metab 94:61-67.
  3. Goodman, SI, et al. (2002) Mol Genet Metab 77(1-2):86-90.
  4. Spaan, AN, et al. (2005) Mol Genet Metab 86(14):441-447.
  5. Olsen, RKJ, et al (2003) Hum Mutat 22:12-23.
  6. Gordon, N. (2006) Brain Dev 28(3):136-140.
  7. Schiff, M, et al. (2006) Mol Genet Metab 88(2):153-158.
  8. Olsen, RKJ, et al., (2007) Brain 130:2045-2054.

Forms and Documents

Test Details

ETFB
  • Diagnostic confirmation
  • Carrier testing
  • Prenatal diagnosis in at-risk pregnancies
  • Capillary Sequencing

Ordering

279
4-5 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 277.87 Disorders of mitochondrial metabolism, Kearns-Sayre syndrome, Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes (MELAS syndrome), Mitochondrial Neurogastrointestinal Encephalopathy syndrome (MNGIE), Myoclonus with Epilepsy and with Ragged Red Fibers (MERRF syndrome), Neuropathy, Ataxia and Retinitis Pigmentosa (NARP syndrome)
* For price inquiries please email zebras@genedx.com

References

  1. Wen et al., (2010) J Neurosurg Psychiatry 81:231-236.
  2. Yotsumoto et al., (2008) Mol Genet Metab 94:61-67.
  3. Olsen, RKJ, et al., (2007) Brain 130:2045-2054.
  4. Goodman, SI, et al. (2002) Mol Genet Metab 77(1-2):86-90.
  5. Spaan, AN, et al. (2005) Mol Genet Metab 86(14):441-447.
  6. Gordon, N. (2006) Brain Dev 28(3):136-140.
  7. Olsen, RKJ, et al (2003) Hum Mutat 22:12-23.
  8. Schiff, M, et al. (2006) Mol Genet Metab 88(2):153-158.

Forms and Documents

Test Details

ETFDH
  • Diagnostic confirmation
  • Carrier testing
  • Prenatal diagnosis in at-risk pregnancies
  • Capillary Sequencing

Ordering

280
4-5 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 277.87 Disorders of mitochondrial metabolism, Kearns-Sayre syndrome, Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes (MELAS syndrome), Mitochondrial Neurogastrointestinal Encephalopathy syndrome (MNGIE), Myoclonus with Epilepsy and with Ragged Red Fibers (MERRF syndrome), Neuropathy, Ataxia and Retinitis Pigmentosa (NARP syndrome)
* For price inquiries please email zebras@genedx.com

References

  1. Wen et al., (2010) J Neurosurg Psychiatry 81:231-236.
  2. Olsen, RKJ, et al., (2007) Brain 130:2045-2054.
  3. Yotsumoto et al., (2008) Mol Genet Metab 94:61-67.
  4. Goodman, SI, et al. (2002) Mol Genet Metab 77(1-2):86-90.
  5. Spaan, AN, et al. (2005) Mol Genet Metab 86(14):441-447.
  6. Olsen, RKJ, et al (2003) Hum Mutat 22:12-23.
  7. Gordon, N. (2006) Brain Dev 28(3):136-140.
  8. Schiff, M, et al. (2006) Mol Genet Metab 88(2):153-158.

Forms and Documents

Test Details

ACAD8, ACADS, ETFA, ETFB, ETFDH, ETHE1
  • Molecular confirmation of a suspected biochemical diagnosis.
  • Testing of patients suspected of having a creatine deficiency syndrome.
  • Prenatal diagnosis for known familial mutation(s) in at-risk pregnancies
  • Next-Gen Sequencing
  • Deletion/Duplication Analysis

Ordering

J980
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81405x1; 81479x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Wolfe L, Jethva R, Oglesbee D, et al. Short-Chain Acyl-CoA Dehydrogenase Deficiency. 2011 Sep 22 [Updated 2014 Aug 7]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017
  2. Roe CR, Cederbaum SD, Roe DS, Sweetman L, et al. Isolated isobutyryl-CoA dehydrogenase deficiency: an unrecognized defect in human valine metabolism. Mol
  3. Gregersen et al. (2001) Hum Mutat 18 (3):169-189 (PMID: 11524729)
  4. Corydon et al. (2001) Pediatr Res 49(1): 18-23 (PMID: 11134486)
  5. Gallant et al. (2012) Mol Genet Metab 106(1) :55-61 (PMID: 22424739)
  6. Di Meo I, Lamperti C, Tiranti V. Ethylmalonic Encephalopathy. 2017 Sep 21. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
  7. Rinaldo P., Cowan TP, and Matern D. Acylcarnitine profile analysis. Genetics in Medicine. 2008;10(2):151.
  8. Multiple Acyl-CoA Dehydrogenase Deficiency; MADD. omim.org. https://www.omim.org/entry/231680?search=231680&highlight=231680. Updated July 9, 2016. Accessed November 29, 2017.