HMG-CoA Lyase Deficiency

3-Hydroxy-3-methylglutaryl-CoA lyase deficiency, commonly known as HMG-CoA lyase deficiency, is a rare inborn error that affects ketogenesis and leucine catabolism. Symptoms usually appear in the first year of life and include metabolic acidosis with hypoketotic hypoglycemia, hyperammonemia, abnormal liver function tests, vomiting and hypotonia. Other signs are hepatomegaly, macrocephaly, and less frequently microcephaly, seizures, acute pancreatitis, dilated cardiomyopathy and arrhythmia. Abnormal cerebral white matter foci on MRI has also been reported. Without treatment, rapid progression to coma and death or permanent neurological damage may occur. With treatment, many patients do well; however recurrent metabolic decompensation continues to occur especially with prolonged fasting or intercurrent illness. This disorder is fatal in approximately 20% of cases with the symptoms becoming milder after childhood.

Tests Available

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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

HMGCL
  • Confirmation of biochemical diagnosis
  • Carrier testing
  • Prenatal diagnosis in at risk pregnancies
  • Capillary Sequencing

Ordering

3212
2-3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81479x1
No
Yes
  • 277.85 Disorders of fatty acid oxidation, Carnitine palmitoyltransferase deficiencies, Glutaric aciduria type II, Long chain 3-hydroxyacyl CoA dehydrogenase deficiency (LCHAD), Long chain/very long chain acyl CoA dehydrogenase deficiency, Medium chain acyl CoA dehydrogenase deficiency (MCAD), Short chain acyl CoA dehydrogenase deficiency (SCAD)
  • 270.3 Disturbances of branched-chain amino-acid metabolism, Disturbances of metabolism of leucine, isoleucine, and valine, Hypervalinemia Intermittent branched-chain ketonuria, Leucine-induced hypoglycemia, Leucinosis, Maple syrup urine disease
* For price inquiries please email zebras@genedx.com

References

  1. Pie et al., (2007) Mol Genet Metab 92:198-209
  2. Al-Sayed et al., (2006) BMC Med Genet 7:86
  3. Cardoso et al., (2004) Mol Genet Metab 82:334-338
  4. Muroi et al., (2000) Hum Genet 107:320-326
  5. Menao et al., (2009) Hum Mutat 30:E520-9

Forms and Documents

Test Details

HMGCL
  • Confirmation of biochemical diagnosis
  • Carrier testing
  • Prenatal diagnosis in at risk pregnancies
  • Capillary Sequencing

Ordering

3211
4-5 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 277.85 Disorders of fatty acid oxidation, Carnitine palmitoyltransferase deficiencies, Glutaric aciduria type II, Long chain 3-hydroxyacyl CoA dehydrogenase deficiency (LCHAD), Long chain/very long chain acyl CoA dehydrogenase deficiency, Medium chain acyl CoA dehydrogenase deficiency (MCAD), Short chain acyl CoA dehydrogenase deficiency (SCAD)
  • 270.3 Disturbances of branched-chain amino-acid metabolism, Disturbances of metabolism of leucine, isoleucine, and valine, Hypervalinemia Intermittent branched-chain ketonuria, Leucine-induced hypoglycemia, Leucinosis, Maple syrup urine disease
* For price inquiries please email zebras@genedx.com

References

  1. Al-Sayed et al., (2006) BMC Med Genet 7:86
  2. Cardoso et al., (2004) Mol Genet Metab 82:334-338
  3. Muroi et al., (2000) Hum Genet 107:320-326
  4. Menao et al., (2009) Hum Mutat 30:E520-9
  5. Pie et al., (2007) Mol Genet Metab 92:198-209

Forms and Documents

Test Details

HMGCL
  • Confirmation of biochemical diagnosis
  • Carrier testing
  • Prenatal diagnosis in at risk pregnancies
  • Capillary Sequencing

Ordering

3213
3-4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 277.85 Disorders of fatty acid oxidation, Carnitine palmitoyltransferase deficiencies, Glutaric aciduria type II, Long chain 3-hydroxyacyl CoA dehydrogenase deficiency (LCHAD), Long chain/very long chain acyl CoA dehydrogenase deficiency, Medium chain acyl CoA dehydrogenase deficiency (MCAD), Short chain acyl CoA dehydrogenase deficiency (SCAD)
  • 270.3 Disturbances of branched-chain amino-acid metabolism, Disturbances of metabolism of leucine, isoleucine, and valine, Hypervalinemia Intermittent branched-chain ketonuria, Leucine-induced hypoglycemia, Leucinosis, Maple syrup urine disease
* For price inquiries please email zebras@genedx.com

References

  1. Menao et al., (2009) Hum Mutat 30:E520-9
  2. Muroi et al., (2000) Hum Genet 107:320-326
  3. Cardoso et al., (2004) Mol Genet Metab 82:334-338
  4. Al-Sayed et al., (2006) BMC Med Genet 7:86
  5. Pie et al., (2007) Mol Genet Metab 92:198-209

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)