Ketotic hypoglycaemia (Version 1.9)

Description

Ketotic hypoglycaemia eligibility statement:

Specific metabolic abnormalities eligibility statements.

Specific Metabolic Abnormalities inclusion criteria (29455)
- Evidence of inborn error of metabolism as demonstrated by findings in at least 2 of the following areas:
  - Clinical presentation
  - Biochemical
  - Haematological
  - Radiological
- Biochemical testing and genetic testing completed for relevant known inborn errors of metabolism

Specific Metabolic Abnormalities exclusion criteria (29455)

Prior genetic testing guidance (29455)
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. 
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.  

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Specific Metabolic Abnormalities prior genetic testing genes (29455)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: 
 - Genetic testing completed for relevant known inborn errors of metabolism

Closing statement (29455)
These requirements will be kept under continual review during the main programme and may be subject to change.

Panel Activity

5 reviewers

Ellen McDonagh (Genomics England Curator)

Group: Other
Workplace: Other
Alexander Broomfield (Central Manchester Foundation Trust)

Group: NHS Genomic Medicine Centre
Workplace: Other clinical service
Sarah Leigh (Genomics England Curator)

Group: Other
Workplace: Other
Louise Daugherty (Genomics England Curator)

Group: Other
Workplace: Other
Catherine Snow (Genomics England)

Group: Other
Workplace: Other

45 Entities

45 reviewed, 27 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 45 Entitiess
Green Green List (high evidence)	ACAT1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Fasting intolerance with acidosis, ? residual neurological problems Tags
Green Green List (high evidence)	AGL	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Literature Radboud University Medical Center, Nijmegen UKGTN Phenotypes myopathy, cardiomyopathy and neuropathy possible but mile hepatomegaly and fasting intolerance Glycogen storage disease IIIa, 232400 Glycogen storage disease IIIb, 232400 Glycogen Storage Disease Type III Glycogen Storage Disorders- Liver Glycogen Storage Disorders- Muscle Glycogen Storage Disease Tags
Green Green List (high evidence)	ALDOA	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Radboud University Medical Center, Nijmegen UKGTN Phenotypes Glycogen storage disease XII, 611881 Glycogen Storage Disease Tags
Green Green List (high evidence)	ALDOB	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes acidosis with ketototic hypoglycaemia often hepatomegaly in acute presentation hereditary fructose intolerance Tags
Green Green List (high evidence)	BTD	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes lactic acidosis with seizures and eczema,immune deficiency Tags
Green Green List (high evidence)	FBP1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green UKGTN Phenotypes Glycogen Storage Disorders- Liver Glycogen Storage Disease Tags
Green Green List (high evidence)	G6PC	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Literature Radboud University Medical Center, Nijmegen UKGTN Phenotypes Glycogen storage disease Ia, OMIM:232200 Tags new-gene-name
Green Green List (high evidence)	GBE1	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Literature Radboud University Medical Center, Nijmegen UKGTN Phenotypes Glycogen storage disease IV, OMIM:232500 Polyglucosan body disease, adult form, OMIM:263570 Tags
Green Green List (high evidence)	GYS2	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Literature Radboud University Medical Center, Nijmegen UKGTN Phenotypes fasting intolerance without enlarged liver Glycogen storage disease, type 0, 240600 Glycogen Storage Disease Type 0, Liver Glycogen Storage Disorders- Liver Glycogen Storage Disease Tags
Green Green List (high evidence)	HLCS	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes lactic acidosis with seizures and eczema, immune deficiency Holocarboxylase synthetase deficiency Tags
Green Green List (high evidence)	IVD	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections. Tags
Green Green List (high evidence)	LDHA	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Glycogen Storage Disease Glycogen storage disease XI, 612933 Tags
Green Green List (high evidence)	MCEE	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Expert Review Green Illumina TruGenome Clinical Sequencing Services Literature Radboud University Medical Center, Nijmegen UKGTN Phenotypes metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections Methylmalonyl-CoA epimerase deficiency Tags
Green Green List (high evidence)	MUT	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections. Tags new-gene-name
Green Green List (high evidence)	OXCT1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes severe ketosis on fasting often ketotic in fed state no hepatomegaly Succinyl CoA:3-oxoacid CoA transferase deficiency Tags
Green Green List (high evidence)	PC	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Pyruvate carboxylase deficiency, OMIM:266150 Tags
Green Green List (high evidence)	PCCA	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections Propionicacidemia Propionic acidemia Tags
Green Green List (high evidence)	PCCB	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes as PCCA (metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections) Propionicacidemia Propionic acidemia Tags
Green Green List (high evidence)	PGM1	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Glycogen storage disease XIV, 612934 Congenital disorder of glycosylation, type It, 614921 Glycogen Storage Disease Type XIV Glycogen Storage Disorders- Muscle Glycogen Storage Disease Tags
Green Green List (high evidence)	PHKA2	2 reviews 1 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Emory Genetics Laboratory Expert Review Green Literature Radboud University Medical Center, Nijmegen UKGTN Phenotypes hepatomegaly and mild hypoglycaemia Glycogen storage disease, type IXa1, 306000 Glycogen storage disease, type IXa2, 306000 Glycogen Storage Disorders- Liver Glycogen Storage Disease Tags
Green Green List (high evidence)	PHKB	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Literature UKGTN Phenotypes hepatomegaly and variable myopathy Glycogen Storage Disorders- Liver Glycogen Storage Disorders- Muscle Glycogen Storage Disease Tags
Green Green List (high evidence)	PHKG2	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Literature Radboud University Medical Center, Nijmegen UKGTN Phenotypes hepatomegaly and variable myopathy Glycogen storage disease IXc, 613027 Cirrhosis due to liver phosphorylase kinase deficiency Glycogen Storage Disorders- Liver Glycogen Storage Disease Tags
Green Green List (high evidence)	PYGL	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Literature Radboud University Medical Center, Nijmegen UKGTN Phenotypes hepatomegaly and mild hypoglycaemia Glycogen storage disease VI, 232700 Glycogen Storage Disease Type VI Glycogen Storage Disorders- Liver Glycogen Storage Disease Tags
Green Green List (high evidence)	SLC16A1	2 reviews	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green Phenotypes Erythrocyte lactate transporter defect, OMIM:245340 Hyperinsulinemic hypoglycemia, familial, 7, OMIM:610021 Monocarboxylate transporter 1 deficiency, OMIM:616095 Tags
Green Green List (high evidence)	SLC2A2	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Literature UKGTN Phenotypes renal falcon syndrome, aminoaciduria phosphaturia, small stature, malabsorption, hepatomegaly and nephromegaly. Glycogen Storage Disorders- Liver Fanconi-Bickel Syndrome Tags
Green Green List (high evidence)	SLC37A4	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Literature Radboud University Medical Center, Nijmegen UKGTN Phenotypes Glycogen storage disease Ib, OMIM:232220 Glycogen storage disease Ic, OMIM:232240 Tags
Green Green List (high evidence)	TANGO2	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green Phenotypes Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration 616878 Tags
Red Red List (low evidence)	ABCC8	2 reviews 1 red	Unknown	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Hyperinsulinemic hypoglycemia, familial, 1, 256450 Hypoglycemia of infancy, leucine-sensitive, 240800 Diabetes mellitus, transient neonatal 2, 610374 Diabetes mellitus, noninsulin-dependent, 125853 Diabetes mellitus, noninsulin-dependent, 125854 Tags
Red Red List (low evidence)	BAAT	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes choleostatic liver disease Tags
Red Red List (low evidence)	ENO3	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Red Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Glycogen storage disease XIII, 612932 Glycogen Storage Disease Type XIII Glycogen Storage Disorders- Muscle Glycogen Storage Disease Tags
Red Red List (low evidence)	EPM2A	2 reviews 1 red	Unknown	Sources Expert Review Red UKGTN Phenotypes Glycogen Storage Disease Tags
Red Red List (low evidence)	FBP2	2 reviews 1 red	Unknown	Sources Expert Review Red UKGTN Phenotypes Glycogen Storage Disease Tags
Red Red List (low evidence)	GAA	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Red Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Glycogen storage disease II, 232300 Glycogen Storage Disease, Type II Glycogen Storage Disorders- Muscle Glycogen Storage Disease Glycogen Storage Disease II Tags
Red Red List (low evidence)	GYG1	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Radboud University Medical Center, Nijmegen UKGTN Phenotypes Glycogen storage disease XV, 613507 Glycogen Storage Disease Tags
Red Red List (low evidence)	GYG2	2 reviews	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert Review Red UKGTN Phenotypes Glycogen Storage Disease Tags
Red Red List (low evidence)	GYS1	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Red Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Glycogen storage disease 0, muscle, 611556 Glycogen Storage Disease Type 0, Muscle Glycogen Storage Disorders- Muscle Glycogen Storage Disease Tags
Red Red List (low evidence)	LAMP2	2 reviews 1 red	Unknown	Sources Emory Genetics Laboratory Expert Review Red UKGTN Phenotypes Glycogen Storage Disorders- Muscle Glycogen Storage Disease Tags
Red Red List (low evidence)	NHLRC1	2 reviews 1 red	Unknown	Sources Expert Review Red UKGTN Phenotypes Glycogen Storage Disease Tags
Red Red List (low evidence)	PFKL	2 reviews	Unknown	Sources Expert Review Red UKGTN Phenotypes Glycogen Storage Disease Hemolytic anemia due to phosphofructokinase deficiency Tags
Red Red List (low evidence)	PFKM	1 review 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Red Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Glycogen storage disease VII, 232800 Glycogen Storage Disease Type VII Glycogen Storage Disorders- Muscle Glycogen Storage Disease Tags
Red Red List (low evidence)	PGAM2	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Red Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Glycogen storage disease X, 261670 Glycogen Storage Disease Type X Glycogen Storage Disorders- Muscle Glycogen Storage Disease Tags
Red Red List (low evidence)	PGK1	2 reviews 1 red	Unknown	Sources Expert Review Red UKGTN Phenotypes Glycogen Storage Disease Tags
Red Red List (low evidence)	PRKAG2	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Emory Genetics Laboratory Expert Review Red Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Wolff-Parkinson-White syndrome, 194200 Cardiomyopathy, familial hypertrophic 6, 600858 Glycogen storage disease of heart, lethal congenital, 261740 Glycogen Storage Disease of Heart, Lethal Congenital Glycogen Storage Disorders- Muscle Tags
Red Red List (low evidence)	PYGM	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Red Illumina TruGenome Clinical Sequencing Services UKGTN Phenotypes Glycogen Storage Disease Type V Glycogen Storage Disease V (McArdle Disease) Glycogen Storage Disorders- Muscle Glycogen Storage Disease Glycogen Storage Disease V Tags
Red Red List (low evidence)	SLC27A5	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes choleostatic jaundice and hepatomegaly Tags

Major version comments

14.06.2016 - Revised the panel according to expert review, and promoted to Version 1.

Ketotic hypoglycaemia (Version 1.9)

5 reviewers

45 Entities

45 reviewed, 27 green

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