Homocystinuria-megaloblastic Anemia, Cblg Complementation Type; Hmag

Description

Homocystinuria and megaloblastic anemia is an autosomal recessive inborn error of metabolism resulting from defects in the cobalamin (vitamin B12)-dependent pathway that converts homocysteine to methionine, which is catalyzed by methionine synthase. Clinical features are somewhat variable, but include delayed psychomotor development, megaloblastic anemia, homocystinuria, and hypomethioninemia, all of which respond to cobalamin supplementation. Methylmalonic aciduria is not present. Two complementation groups have been described based on fibroblast studies: CblE (OMIM ) and CblG (Watkins and Rosenblatt, 1988). Most patients present in early infancy, but some patients with CblG have shown later onset (Outteryck et al., 2012). Cells from patients with CblE fail to incorporate methyltetrahydrofolate into methionine in whole cells, but cell extracts show normal methionine synthase activity in the presence of a reducing agent. Cells from patients with CblG have defects in the methionine synthase enzyme under both conditions (summary by Leclerc et al., 1996).CblE is caused by mutation in the MTRR gene (OMIM ).Watkins and Rosenblatt (1989) commented on the clinical and biochemical heterogeneity in patients with cblE and cblG.

Clinical Features

Top most frequent phenotypes and symptoms related to Homocystinuria-megaloblastic Anemia, Cblg Complementation Type; Hmag

  • Intellectual disability
  • Seizures
  • Global developmental delay
  • Short stature
  • Generalized hypotonia
  • Microcephaly
  • Ataxia
  • Growth delay
  • Nystagmus
  • Failure to thrive
And another 49 symptoms. If you need more information about this disease we can help you.
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Incidence and onset information

Not enough data available about incidence and published cases.


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Homocystinuria-megaloblastic Anemia, Cblg Complementation Type; Hmag Recommended genes panels

Panel Name, Specifity and genes Tested/covered
MitoMet®Plus aCGH Analysis.

By Baylor Miraca Genetics Laboratories in United States.

BRCA1, MTHFR, UBE3A, VHL, MUTYH, TP53, MCCC1, MCCC2, AARS2, ABCB11, ABCB4, ABHD12, ACACA, ACAD9, ACADM, ACADS, AGL, ACADVL, ACAT1, ZNF513 , (...)

View the complete list with 617 more genes
Specificity
1 %
Genes
100 %
Cobalamin Metabolism Panel (MitomeNGS).

By Baylor Miraca Genetics Laboratories in United States.

MMACHC, MTR, MTRR, MMADHC, LMBRD1, TCN2, MMAB, MMAA, MUT
Specificity
12 %
Genes
100 %
MTR Deletion/Duplication Analysis.

By Baylor Miraca Genetics Laboratories in United States.

MTR
Specificity
100 %
Genes
100 %
MTR Familial Mutation/Variant Analysis.

By Baylor Miraca Genetics Laboratories in United States.

MTR
Specificity
100 %
Genes
100 %
MTR Prenatal Sequence Analysis.

By Baylor Miraca Genetics Laboratories in United States.

MTR
Specificity
100 %
Genes
100 %
MTR Sequence Analysis.

By Baylor Miraca Genetics Laboratories in United States.

MTR
Specificity
100 %
Genes
100 %
MTR Sequence and Deletion/Duplication Analysis.

By Baylor Miraca Genetics Laboratories in United States.

MTR
Specificity
100 %
Genes
100 %
Methylmalonic Acidemia Sequencing NextGen Panel.

By Children's Hospital Colorado Molecular Genetics Laboratory Children's Hospital Colorado in United States.

MTHFR, MTR, ACSF3, SUCLA2, TCN2, GIF, MCEE, MMAB, MMAA, IVD, CBS, CD320, TCN1
Specificity
8 %
Genes
100 %
Cobalamin Metabolism Disorder.

By Knight Diagnostic Laboratories - Molecular Diagnostic Center Oregon Health & Science University in United States.

MMACHC, MTR, MTRR, ACSF3, MMADHC, LMBRD1, TCN2, GIF, MCEE, MMAB, MMAA, MUT, SUCLG1, IVD, CBS, ABCD4, CD320
Specificity
6 %
Genes
100 %
Cobalamin/Propionate/Homocysteine Metabolism Related Disorders Panel, Sequencing (25 Genes) and Deletion/Duplication (24 Genes).

By ARUP Laboratories, Molecular Genetics and Genomics in United States.

MTHFR, MMACHC, AMN, MTR, MTRR, ACSF3, SUCLA2, PCCB, PCCA, MMADHC, LMBRD1, TCN2, CUBN, GIF, MCEE, MMAB, MMAA, MUT, SUCLG1, CBS , (...)

View the complete list with 5 more genes
Specificity
4 %
Genes
100 %
NGS Neurodegenerative disorders Multi-Gene Panel (73 genes).

By Laboratory of genome diagnostics Academic Medical Center, University of Amsterdam in Netherlands.

MTHFR, ARG1, HLCS, BCKDHA, BCKDHB, ADSL, MMACHC, MTR, MTRR, CPS1, HPRT1, DLD, COQ9, PDSS2, PDSS1, GAMT, GATM, SPR, COQ8A, COQ2 , (...)

View the complete list with 40 more genes
Specificity
2 %
Genes
100 %
MTR. Complete sequencing.

By Instituto de Medicina Genomica Instituto de Medicina Genomica in Spain.

MTR
Specificity
100 %
Genes
100 %
Homocystinuria-megaloblastic anemia, cblG complementation type (sequence analysis of MTR gene).

By CGC Genetics in Portugal.

MTR
Specificity
100 %
Genes
100 %
Methylmalonic aciduria (NGS panel for 15 genes).

By CGC Genetics in Portugal.

MMACHC, MTR, MTRR, ACSF3, SUCLA2, MMADHC, LMBRD1, MCEE, MMAB, MMAA, MUT, MLYCD, SUCLG1, ABCD4, CD320
Specificity
7 %
Genes
100 %
Homocystinuria, cblG Type, via the MTR Gene.

By PreventionGenetics PreventionGenetics in United States.

MTR
Specificity
100 %
Genes
100 %
Homocystinuria Sequencing Panel with CNV Detection.

By PreventionGenetics PreventionGenetics in United States.

MTHFR, MTR, MTRR, MMADHC, CBS
Specificity
20 %
Genes
100 %
Disorders Related to Metabolism of Cobalamin, Folate and Homocysteine Sequencing Panel with CNV Detection.

By PreventionGenetics PreventionGenetics in United States.

MTHFR, MMACHC, AMN, MTR, MTRR, ACSF3, ALDH6A1, SUCLA2, PCCB, PCCA, MMADHC, LMBRD1, TCN2, CUBN, GIF, MCEE, MMAB, MMAA, MUT, MLYCD , (...)

View the complete list with 11 more genes
Specificity
4 %
Genes
100 %
Mental retardation - different panels.

By Institute of Human Genetics Cologne University in Germany.

FMR1, UBE3A, PTEN, MCCC1, MCCC2, ACAD9, PC, ANKH, HLCS, ATP7A, AUH, B4GALT7, BCKDHA, BCKDHB, BCS1L, C12orf65, ADSL, MMACHC, PRKCG, PAX6 , (...)

View the complete list with 847 more genes
Specificity
1 %
Genes
100 %
Hyperhomocysteinemia due to Methionine synthase deficiency, cblG (MTR).

By VU University Medical Center Metabolic Unit, PX 1X 009 in Netherlands.

MTR
Specificity
100 %
Genes
100 %
Homocystinuria, B12-responsive.

By Centogene AG - the Rare Disease Company in Germany.

MTR
Specificity
100 %
Genes
100 %
AllNeuro panel.

By Centogene AG - the Rare Disease Company in Germany.

F2, F5, FMR1, HTT, HFE, MTHFR, TTR, UBE3A, VHL, PTEN, AARS2, ABHD12, ACACA, ACAD9, ACADL, ACADM, ACADS, AGL, ACADVL, ACAT1 , (...)

View the complete list with 1185 more genes
Specificity
1 %
Genes
100 %
CentoICU platinum plus.

By Centogene AG - the Rare Disease Company in Germany.

BRCA2, F2, F5, MTHFR, UBE3A, MCCC1, MCCC2, AARS2, ACAD9, ACADL, ACADM, ACADS, AGL, ACADVL, ACAT1, ALDOA, ALDOB, FBP1, PC, GYS2 , (...)

View the complete list with 494 more genes
Specificity
1 %
Genes
100 %
CentoICU platinum.

By Centogene AG - the Rare Disease Company in Germany.

BRCA2, F2, F5, MTHFR, UBE3A, MCCC1, MCCC2, AARS2, ACAD9, ACADL, ACADM, ACADS, AGL, ACADVL, ACAT1, ALDOA, ALDOB, FBP1, PC, GYS2 , (...)

View the complete list with 494 more genes
Specificity
1 %
Genes
100 %
Methylcobalamin deficiency CblG type.

By Centogene AG - the Rare Disease Company in Germany.

MTR
Specificity
100 %
Genes
100 %
Methylmalonic Aciduria and Homocystinuria.

By Asper Biogene Asper Biogene LLC in Estonia.

MTHFR, MMACHC, AMN, MTR, MTRR, ACSF3, SUCLA2, MMADHC, LMBRD1, TCN2, CUBN, GIF, MCEE, MMAB, MMAA, MUT, MLYCD, SUCLG1, IVD, CBS , (...)

View the complete list with 3 more genes
Specificity
5 %
Genes
100 %
Invitae Homocystinuria Panel.

By Invitae in United States.

MTHFR, MTR, MTRR, CBS
Specificity
25 %
Genes
100 %
Invitae Metabolic Disorders Newborn Screening Confirmation Panel.

By Invitae in United States.

MCCC1, MCCC2, ACADM, ACADS, ACADVL, ACAT1, PC, ARG1, HLCS, BTD, AUH, BCKDHA, BCKDHB, GAA, MMACHC, MTR, MTRR, CPS1, CPT2, PRODH , (...)

View the complete list with 70 more genes
Specificity
2 %
Genes
100 %
Invitae Treatable Neurometabolic Disorders Panel.

By Invitae in United States.

MTHFR, MCCC1, MCCC2, ACAT1, ARG1, HLCS, ATP7A, BTD, ATP7B, AUH, BCKDHA, BCKDHB, MMACHC, AMN, MTR, MTRR, CPS1, HSD17B10, DLD, SLC25A13 , (...)

View the complete list with 72 more genes
Specificity
2 %
Genes
100 %
Inherited Metabolic Disorders: Sequencing Panel.

By EGL Genetic Diagnostics Eurofins Clinical Diagnostics in United States.

MCCC1, MCCC2, ACAD9, ACADL, ACADM, ACADS, AGL, ACADVL, PC, GYS2, HLCS, ATPAF2, AUH, BCKDHA, BCKDHB, GAA, MMACHC, MTR, SLC37A4, MTRR , (...)

View the complete list with 81 more genes
Specificity
1 %
Genes
100 %
Cobalamin Homocysteine Methionine Deficiency NGS Panel.

By Fulgent Genetics Fulgent Genetics in United States.

MTHFR, MMACHC, MTR, MTRR, ALDH6A1, MMADHC, LMBRD1, TCN2, MCEE, MMAB, MMAA, MUT, CBS, AHCY, GNMT, CD320, MAT1A, CTH, ADK, FOLH1
Specificity
5 %
Genes
100 %
Intellectual Disability NGS Panel.

By Fulgent Genetics Fulgent Genetics in United States.

BRCA2, F5, FMR1, MTHFR, TTR, UBE3A, PTEN, MCCC1, MCCC2, AGL, ACAT1, GYS2, ARG1, ATP7A, AUH, BCS1L, ADSL, FBLN5, LRP5, COL1A2 , (...)

View the complete list with 372 more genes
Specificity
1 %
Genes
100 %
MTR.

By Fulgent Genetics Fulgent Genetics in United States.

MTR
Specificity
100 %
Genes
100 %
Organic Acidemia/Aciduria & Cobalamin Deficiency Panel.

By Blueprint Genetics in Finland.

MTHFR, MCCC1, MCCC2, ACAT1, BCKDHA, BCKDHB, BCS1L, MMACHC, AMN, MTR, MTRR, DLD, ACSF3, HMGCL, IDH2, ACADSB, PCCB, PCCA, D2HGDH, MMADHC , (...)

View the complete list with 33 more genes
Specificity
2 %
Genes
100 %
Comprehensive Hematology Panel.

By Blueprint Genetics in Finland.

BRCA1, BRCA2, F2, F5, HFE, EPCAM, MSH2, PMS2, MSH6, MLH1, RECQL4, RUNX1, TP53, YARS2, PC, HBB, TYRP1, OCA2, AMN, SLC45A2 , (...)

View the complete list with 219 more genes
Specificity
1 %
Genes
100 %
Comprehensive Metabolism Panel.

By Blueprint Genetics in Finland.

HFE, MTHFR, MCCC1, MCCC2, ACAD9, ACADL, ACADM, ACADS, AGL, ACADVL, ACAT1, ALDOA, ALDOB, FBP1, PC, GYS2, ARG1, HLCS, BTD, ATP7B , (...)

View the complete list with 414 more genes
Specificity
1 %
Genes
100 %
Anemia Panel.

By Blueprint Genetics in Finland.

BRCA2, HFE, YARS2, PC, HBB, AMN, MTR, CLCN7, ALAS2, GPI, RPL35A, PUS1, PDHA1, ABCB7, TCN2, NT5C3A, CUBN, CYB5R3, SLC25A38, PDHX , (...)

View the complete list with 58 more genes
Specificity
2 %
Genes
100 %
Homocystinuria Core Panel.

By Blueprint Genetics in Finland.

MTHFR, MTR, MTRR, CBS
Specificity
25 %
Genes
100 %
HOMOCYSTINURIA-MEGALOBLASTIC ANEMIA, cblG COMPLEMENTATION TYPE; HMAG.

By Bioarray in Spain.

MTR
Specificity
100 %
Genes
100 %
Baby Genes Targeted Panel.

By Baby Genes Inc. Baby Genes Inc. in United States.

MTHFR, MCCC1, MCCC2, ACADM, ACADS, ACADVL, ACAT1, ARG1, HLCS, BTD, BCKDHA, BCKDHB, GAA, HBB, MMACHC, MTR, MTRR, CPT2, DLD, SLC25A13 , (...)

View the complete list with 70 more genes
Specificity
2 %
Genes
100 %
METHYLCOBALAMIN DEFICIENCY.

By Laboratorio de Genetica Clinica SL in Spain.

MTR, MTRR, MMADHC
Specificity
34 %
Genes
100 %
MMADHC.

By Laboratorio de Genetica Clinica SL in Spain.

MTR, MTRR, MMADHC
Specificity
34 %
Genes
100 %
Homocystinuria caused by Cystathionine Beta-Synthase Deficiency, Sequencing MTR Gene.

By Reference Laboratory Genetics in Spain.

MTR
Specificity
100 %
Genes
100 %
Neural Tube Defects and Related Disorders , Panel Massive Sequencing (NGS) 9 Genes.

By Reference Laboratory Genetics in Spain.

MTHFR, MMACHC, MTR, MTRR, CCL2, VANGL1, VANGL2, FUZ, MTHFD1
Specificity
12 %
Genes
100 %
Homocystinuria: gene sequencing panel (RAPID testing).

By CEN4GEN Institute for Genomics and Molecular Diagnostics in Canada.

MTHFR, MTR, MTRR, CBS
Specificity
25 %
Genes
100 %
cblG complementation type homocystinuria-megaloblastic anemia: Full gene sequencing (Rapid testing).

By CEN4GEN Institute for Genomics and Molecular Diagnostics in Canada.

MTR
Specificity
100 %
Genes
100 %
CEN4GEN rapid supplemental newborn genetic screen: Full gene sequencing panel.

By CEN4GEN Institute for Genomics and Molecular Diagnostics in Canada.

MTHFR, MCCC1, MCCC2, ACADM, ACADS, ACADVL, ACAT1, ARG1, HLCS, BTD, AUH, BCKDHA, BCKDHB, GAA, HBB, MMACHC, MTR, MTRR, CPT2, HSD17B10 , (...)

View the complete list with 79 more genes
Specificity
2 %
Genes
100 %
CEN4GEN rapid pan-ethnic carrier screen: Full gene sequencing panel.

By CEN4GEN Institute for Genomics and Molecular Diagnostics in Canada.

MTHFR, MCCC1, MCCC2, ACADM, ACADS, ACADVL, ACAT1, ARG1, HLCS, BTD, AUH, BCKDHA, BCKDHB, GAA, HBB, MMACHC, MTR, MTRR, CPT2, HSD17B10 , (...)

View the complete list with 84 more genes
Specificity
1 %
Genes
100 %

Alternate names

Homocystinuria-megaloblastic Anemia, Cblg Complementation Type; Hmag Is also known as homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism, cblg complementation type, methylcobalamin deficiency, cblg type, methionine synthase deficiency;functional methionine synthase deficiency type cblg.



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