Atypical haemolytic uraemic syndrome

Gene: MMACHC

Green List (high evidence)

MMACHC (methylmalonic aciduria (cobalamin deficiency) cblC type, with homocystinuria)
EnsemblGeneIds (GRCh38): ENSG00000132763
EnsemblGeneIds (GRCh37): ENSG00000132763
OMIM: 609831, Gene2Phenotype
MMACHC is in 21 panels

2 reviews

David Kavanagh (Newcastle upon Tyne NHS hospitals trust)

Green List (high evidence)

MMACHC is a cause of Eculizumab non responsive aHUS. Identification of the genetic abnormality in aHUS prevents ineffective treatment with Eculizumab and alolows appropriate treatment with VitB12 therapy.
Created: 6 Aug 2019, 8:56 a.m. | Last Modified: 6 Aug 2019, 8:56 a.m.
Panel Version: 1.9

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
OMIM 277400

Publications

Variants in this GENE are reported as part of current diagnostic practice

Eleanor Williams (Genomics England Curator)

I don't know

Comment on list classification: Changing rating from red to green. More than 3 cases, with different variants reported, although in one case the healthy sister also had the same variants as the proband.
Created: 14 Aug 2019, 5:34 p.m. | Last Modified: 14 Aug 2019, 5:34 p.m.
Panel Version: 1.10
Associated with Methylmalonic aciduria and homocystinuria, cblC type (#277400) in OMIM.

PMID: 29068997 - Chen et al 2017 - 4-year-old girl with a diagnosis of aHUS. Genetic analysis revealed a compound heterozygous MMACHC mutation exonl: c. 80A >G, c. 609G >A. After treated by vitamin B12 for 10 days, the patient condition significantly improved. Note: her healthy younger sister also had both mutations. Her parents each had one of the variants.

PMID: 27324188 - Adrovic et al 2016 - describe the case of a 6-year-old girl with cblC disorder, who presented with severe multiorgan involvement at the age of 5 months and who was successfully treated with vitamin B12, betaine, coenzyme Q10 and l-carnitene, and who had a new homozygous mutation of MMACHC c. 484G > T, p.Gly162Trp

PMID: 24210589 - Cornec-Le Gall et al 2014 - Abstract only accessed. Describe a patient with atypical hemolytic uremic syndrome that did not respond to eculizumab. Very low plasma methionine levels associated with methylmalonic aciduria, which suggested cobalamin C disease. MMACHC sequencing revealed compound heterozygosity for 2 causative mutations.

PMID: 17874135 - Sharma et al 2007 - report a child diagnosed with Diarrhea-negative HUS secondary to cblC disease in infancy. Mutation analysis in this patient identified homozygosity for the 271 dupA mutation (c.271 dupA) in the cblC MMACHC gene.

PMID: 12210350 - Van Hove et al 2002 - Abstract only accessed. Report 2 siblings,with proteinuria and hematuria, hypertension, and chronic hemolytic anemia. Both patients had hyperhomocysteinemia and mild methylmalonic aciduria. Both patients and their father carry a balanced reciprocal translocation but the abstract does not state where in the genome this is.

PMID: 1593355 - Geraghty et al 1992 - Abstract only accessed. Describe a female infant with typical features of the cobalamin C form of combined methylmalonic aciduria and homocystinuria who also had the hemolytic-uremic syndrome with thrombocytopenia, microangiopathic hemolytic anemia, hypertension, and renal failure. No sequencing of the gene reported in the abstract.

PMID: 11972107 - Kind et al 2002 - a case of cobalamin C disease associated with hemolytic-uremic syndrome (HUS) in the neonatal period is described. No sequencing of the gene reported.
Created: 14 Aug 2019, 5:31 p.m. | Last Modified: 14 Aug 2019, 5:36 p.m.
Panel Version: 1.13
This gene was part of an initial gene list collated by Valerie Wilson, The National Renal Complement Therapeutics Centre, February 2019 on behalf of Yorkshire and North East GLH for the GMS Renal Specialist Test Group; Gene Symbol submitted: MMACHC; Suggested initial gene rating: none provided;
Created: 12 Feb 2019, 12:40 p.m.

History Filter Activity

14 Aug 2019, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: MMACHC were changed from to Methylmalonic aciduria and homocystinuria, cblC type, 277400

14 Aug 2019, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: MMACHC were set to

14 Aug 2019, Gel status: 3

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: MMACHC was changed from to BIALLELIC, autosomal or pseudoautosomal

14 Aug 2019, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: mmachc has been classified as Green List (High Evidence).

12 Feb 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Eleanor Williams (Genomics England Curator)

gene: MMACHC was added gene: MMACHC was added to Atypical haemolytic uraemic syndrome. Sources: NHS GMS Mode of inheritance for gene: MMACHC was set to