Neonatal cholestasis

Gene: ADK

Green List (high evidence)

ADK (adenosine kinase)
EnsemblGeneIds (GRCh38): ENSG00000156110
EnsemblGeneIds (GRCh37): ENSG00000156110
OMIM: 102750, Gene2Phenotype
ADK is in 4 panels

2 reviews

Anna de Burca (Genomics England Curator)

Comment on list classification: There are 18 reported cases in 13 unrelated families of homozygous or compound heterozygous variants in this gene associated with hypermethioninaemia and (in most cases) conjugated hyperbilirubinaemia; liver biopsy in 4 cases demonstrated cholestasis. Some cases responded to methionine restriction, justifying the 'treatable' tag.
Created: 27 Jul 2018, 5:07 a.m.
Comment on publications: In PMID:26642971, in 9/11 cases, first presentation was usually with severe or prolonged conjugated hyperbilirubinaemia and hypoglycaemia; all patients except patients 9 and 10 (family VII) had intermittent increases of liver enzymes and/or cholestasis. Although this led the authors to conclude that ‘hepatic involvement is not a constant finding’, note that family VII were homozygous for a variant that has been classified as a VUS in ClinVar.
Created: 27 Jul 2018, 4:52 a.m.

Ellen McDonagh (Genomics England Curator)

Comment on list classification: More than 3 unrelated cases/families reported with homozygous variants in this gene and Hypermethioninemia due to adenosine kinase deficiency. In PMID: 21963049 liver biopsies for 4 cases revealed cholestasis in 3 cases. For the Swedish sublings reported, both were investigated for failure to thrive in the neonatal period and the older brother was also investigated for prolonged conjugated hyperbilirubinemia. Reduced activity was displayed in vitro assays with the variants identified compared to wild type.
Created: 25 Jul 2018, 3:39 p.m.
Comment on publications: PMID: 27500280 - a case report of a 3-year old girl with a history of poor feeding, irritability, respiratory infections, cholestasis, congenital heart disease, neurodevelopmental delay, hypotonia, sparse hair, facial dysmorphisms, liver dysfunction, severe hypermethioninemia and mild homocystinemia. Added the 'treatable' tag as a methionine-restricted diet normalized the liver function test results and improved her hypotonia.
Created: 25 Jul 2018, 3:27 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Victorian Clinical Genetics Services
Phenotypes
  • Hypermethioninemia due to adenosine kinase deficiency 614300
Tags
treatable
OMIM
102750
Clinvar variants
Variants in ADK
Penetrance
None
Publications
Panels with this gene

History Filter Activity

3 Sep 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

This panel has been subjected to extensive internal and external review.

27 Jul 2018, Gel status: 3

Set mode of inheritance

Anna de Burca (Genomics England Curator)

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

27 Jul 2018, Gel status: 3

Entity classified by Genomics England curator

Anna de Burca (Genomics England Curator)

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

27 Jul 2018, Gel status: 3

Entity classified by Genomics England curator

Anna de Burca (Genomics England Curator)

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

27 Jul 2018, Gel status: 2

Set publications

Anna de Burca (Genomics England Curator)

Publications for gene: ADK were set to 27500280; 21963049; 26642971

26 Jul 2018, Gel status: 2

Set publications

Anna de Burca (Genomics England Curator)

Publications for gene: ADK were set to 27500280; 21963049; 26642971

26 Jul 2018, Gel status: 2

Set publications

Anna de Burca (Genomics England Curator)

Publications for gene: ADK were set to 27500280; 21963049; 26642971

25 Jul 2018, Gel status: 2

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: adk has been classified as Amber List (Moderate Evidence).

25 Jul 2018, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for gene: ADK were set to 27500280; 21963049

25 Jul 2018, Gel status: 1

Set Phenotypes

Ellen McDonagh (Genomics England Curator)

Phenotypes for gene: ADK were set to Hypermethioninemia due to adenosine kinase deficiency 614300

25 Jul 2018, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for gene: ADK were set to 27500280

25 Jul 2018, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for gene: ADK were set to 27500280

21 Jun 2018, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

ADK was added to Cholestasis panel. Sources: Victorian Clinical Genetics Services

21 Jun 2018, Gel status: 1

Created

Ellen McDonagh (Genomics England Curator)

ADK was created by Ellen McDonagh