Ethylmalonic Encephalopathy

Ethylmalonic encephalopathy (EE) is a rare metabolic disorder characterized by psychomotor regression and generalized hypotonia, which progresses into spastic tetraparesis, dystonia and global neurological failure. MRI shows necrotic lesions in the basal ganglia and brainstem. The encephalopathy is typically accompanied by petechia and orthostatic acrocyanosis. Chronic diarrhea is also common. Most patients with EE have been from the Mediterranean basin or Arabic peninsula.

Tests Available

Forms and Documents

Test Details

AARS2, ABCB7, ACAD9, ACO2, AFG3L2, AGK, AIFM1, ALAS2, APOPT1, ATP5A1, ATP5E, ATP7B, ATPAF2, AUH, BCS1L, BOLA3, C12ORF65, C19orf12, CARS2, CLPB, COA5, COA6, COASY, COQ2, COQ4, COQ6, COQ7, COQ8A, COQ8B, COQ9, COX10, COX14, COX15, COX20, COX6A1, COX6B1, COX8A, CYC1, DARS2, DGUOK, DLAT, DLD, DNA2, DNAJC19, DNM1L, EARS2, ECHS1, ELAC2, ETFA, ETFB, ETFDH, ETHE1, FARS2, FASTKD2, FBXL4, FDX1L, FH, FLAD1, FOXRED1, GARS, GCDH, GFER, GFM1, GFM2, GLRX5, GTPBP3, GYG2, HARS2, HMGCL, HTRA2, IARS2, IBA57, ISCA2, ISCU, LAMP2, LARS, LARS2, LIAS, LIPT1, LRPPRC, LYRM4, LYRM7, MARS2, MFF, MFN2, MGME1, MICU1, MPC1, MPV17, MRPL12, MRPL3, MRPL44, MRPS16, MRPS22, MRPS7, MTFMT, MTO1, MTPAP, NARS2, NDUFA1, NDUFA10, NDUFA11, NDUFA12, NDUFA2, NDUFA4, NDUFA9, NDUFAF1, NDUFAF2, NDUFAF3, NDUFAF4, NDUFAF5, NDUFAF6, NDUFAF7, NDUFB11, NDUFB3, NDUFB9, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS6, NDUFS7, NDUFS8, NDUFV1, NDUFV2, NFS1, NFU1, NR2F1, NUBPL, OPA1, OPA3, OTC, PARS2, PC, PCCA, PCCB, PDHA1, PDHB, PDHX, PDP1, PDSS1, PDSS2, PET100, PNPT1, POLG, POLG2, PRKAG2, PUS1, QARS, RARS, RARS2, RMND1, RNASEH1, RRM2B, SARS2, SCO1, SCO2, SDHA, SDHAF1, SERAC1, SFXN4, SLC19A2, SLC19A3, SLC22A5, SLC25A26, SLC25A3, SLC25A38, SLC25A4, SLC25A46, SPAST, SPG7, SUCLA2, SUCLG1, SURF1, TACO1, TARS2, TAZ, TFAM, TIMM8A, TK2, TMEM126A, TMEM126B, TMEM70, TPK1, TRIT1, TRMT10C, TRMU, TRNT1, TSFM, TTC19, TUFM, TWNK, TYMP, UQCC2, UQCC3, UQCRB, UQCRC2, UQCRQ, VARS2, WDR45, WFS1, YARS2
  • Molecular confirmation of a clinical diagnosis
  • Testing of patients suspected of having a mitochondrial disorder
  • Prenatal diagnosis for known familial mutation(s) in nuclear genes in at-risk pregnancies.
  • Next-Gen Sequencing
  • Deletion/Duplication Analysis

Ordering

573
6 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81440x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Oliveira et al. (2005) Dev Med Child Neurol 47 (3):185-9 (PMID: 15739723)
  2. Chinnery P. Mitochondrial Disorders Overview 2000 Jun 8 [Updated 2014 Aug 14]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. Available from: https://www.ncbi.nlm.n
  3. Tarnopolsky et al. (2005) Med Sci Sports Exerc 37 (12):2086-93 (PMID: 16331134)
  4. van Adel et al. (2009) Journal Of Clinical Neuromuscular Disease 10 (3):97-121 (PMID: 19258857)
  5. Zhu et al. (2009) Acta Biochim. Biophys. Sin. (Shanghai) 41 (3):179-87 (PMID: 19280056)
  6. Koenig et al. (2008) Pediatr. Neurol. 38 (5):305-13 (PMID: 18410845)
  7. Zeviani et al. (2004) Brain 127 (Pt 10):2153-72 (PMID: 15358637)
  8. Taylor et al. (2014) JAMA 312 (1):68-77 (PMID: 25058219)

Forms and Documents

Test Details

ETHE1
  • Confirmation of biochemical diagnosis
  • Carrier testing
  • Prenatal diagnosis in at risk pregnancies
  • Capillary Sequencing
  • Exon Array CGH

Ordering

558
4-5 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 348.3 Encephalopathy, not elsewhere classified
* For price inquiries please email zebras@genedx.com

References

  1. Mineri et al., (2008) J Med Genet 45:473-478.
  2. Tiranti et al., (2006) J Med Genet 43:340-346.
  3. Tiranti et al., (2009) Nature Med 15:200-205.

Forms and Documents

Test Details

AARS2, ABCB7, ACAD9, ACO2, AFG3L2, AGK, AIFM1, ALAS2, APOPT1, ATP5A1, ATP5E, ATP7B, ATPAF2, AUH, BCS1L, BOLA3, C12ORF65, C19orf12, CARS2, CLPB, COA5, COA6, COASY, COQ2, COQ4, COQ6, COQ7, COQ8A, COQ8B, COQ9, COX10, COX14, COX15, COX20, COX6A1, COX6B1, COX8A, CYC1, DARS2, DGUOK, DLAT, DLD, DNA2, DNAJC19, DNM1L, EARS2, ECHS1, ELAC2, ETFA, ETFB, ETFDH, ETHE1, FARS2, FASTKD2, FBXL4, FDX1L, FH, FLAD1, FOXRED1, GARS, GCDH, GFER, GFM1, GFM2, GLRX5, GTPBP3, GYG2, HARS2, HMGCL, HTRA2, IARS2, IBA57, ISCA2, ISCU, LAMP2, LARS, LARS2, LIAS, LIPT1, LRPPRC, LYRM4, LYRM7, MARS2, MFF, MFN2, MGME1, MICU1, MPC1, MPV17, MRPL12, MRPL3, MRPL44, MRPS16, MRPS22, MRPS7, MTFMT, MTO1, MTPAP, NARS2, NDUFA1, NDUFA10, NDUFA11, NDUFA12, NDUFA2, NDUFA4, NDUFA9, NDUFAF1, NDUFAF2, NDUFAF3, NDUFAF4, NDUFAF5, NDUFAF6, NDUFAF7, NDUFB11, NDUFB3, NDUFB9, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS6, NDUFS7, NDUFS8, NDUFV1, NDUFV2, NFS1, NFU1, NR2F1, NUBPL, OPA1, OPA3, OTC, PARS2, PC, PCCA, PCCB, PDHA1, PDHB, PDHX, PDP1, PDSS1, PDSS2, PET100, PNPT1, POLG, POLG2, PRKAG2, PUS1, QARS, RARS, RARS2, RMND1, RNASEH1, RRM2B, SARS2, SCO1, SCO2, SDHA, SDHAF1, SERAC1, SFXN4, SLC19A2, SLC19A3, SLC22A5, SLC25A26, SLC25A3, SLC25A38, SLC25A4, SLC25A46, SPAST, SPG7, SUCLA2, SUCLG1, SURF1, TACO1, TARS2, TAZ, TFAM, TIMM8A, TK2, TMEM126A, TMEM126B, TMEM70, TPK1, TRIT1, TRMT10C, TRMU, TRNT1, TSFM, TTC19, TUFM, TWNK, TYMP, UQCC2, UQCC3, UQCRB, UQCRC2, UQCRQ, VARS2, WDR45, WFS1, YARS2
  • Molecular confirmation of a clinical diagnosis
  • Testing of patients suspected of having a mitochondrial disorder
  • Prenatal diagnosis for known familial mutation(s) in nuclear genes in at-risk pregnancies.
  • Next-Gen Sequencing
  • Deletion/Duplication Analysis

Ordering

615
6 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81460x1, 81465x1, 81440x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Oliveira et al. (2005) Dev Med Child Neurol 47 (3):185-9 (PMID: 15739723)
  2. Chinnery P. Mitochondrial Disorders Overview 2000 Jun 8 [Updated 2014 Aug 14]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. Available from: https://www.ncbi.nlm.n
  3. Tarnopolsky et al. (2005) Med Sci Sports Exerc 37 (12):2086-93 (PMID: 16331134)
  4. van Adel et al. (2009) Journal Of Clinical Neuromuscular Disease 10 (3):97-121 (PMID: 19258857)
  5. Zhu et al. (2009) Acta Biochim. Biophys. Sin. (Shanghai) 41 (3):179-87 (PMID: 19280056)
  6. Longo et al. (2003) Neurol Clin 21 (4):817-31 (PMID: 14743651)
  7. Koenig et al. (2008) Pediatr. Neurol. 38 (5):305-13 (PMID: 18410845)
  8. Zeviani et al. (2004) Brain 127 (Pt 10):2153-72 (PMID: 15358637)
  9. Taylor et al. (2014) JAMA 312 (1):68-77 (PMID: 25058219)

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.