Research panel - Severe Paediatric Disorders
Gene: HMBS

HMBS (hydroxymethylbilane synthase)
EnsemblGeneIds (GRCh38): ENSG00000256269
EnsemblGeneIds (GRCh37): ENSG00000256269
OMIM: 609806, Gene2Phenotype
HMBS is in 13 panels

2 reviews

Sharon Whatley (International Porphyria Network)

Green List (high evidence)

Relevant metabolic investigation: urine porphobilinogen
Acute intermittent porphyria (AIP), caused by a single pathogenic variant in the HMBS gene usually become symptomatic in early adulthood and is therefore not relevant to this panel.
Careful consideration should be given to the reporting of a single pathogenic variant as an incidental finding in the HMBS gene due to its low penetrance.
PMID: 14262853 De Villeneuve, 1577472 Llewellyn, 15534187 Solis, 14970743 Hessels and 27558376 Dixon, reported biallelic variants in the HMBS gene in six children (5 families).
In these six children the age of onset was from birth to 18 months although 6 other patients who were diagnosed as adults (PMID:34089223 Stutterd, 27558376 Kevelam) had ages of onset from 4 to 22 years. Neurological signs in one or more of the six children included spasticity, ataxia, nystagmus, peripheral neuropathy, decreased muscle tone and reflexes, Babinski signs, apnoeic episodes, seizures and developmental delay. Two of the children had bilateral cataracts and one optic nerve atrophy. In two children where MRI investigations were carried out white matter abnormalities were found. All patients had increased urine porphobilinogen concentrations between 3 and 128 times the normal concentration.
A biallelic finding may lead to diagnosis in these very rare patients.
Created: 4 Apr 2025, 4:18 p.m. | Last Modified: 4 Apr 2025, 4:18 p.m.

Panel Version: 1.211

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
14262853; 1577472; 15534187; 14970743; 27558376; 34089223; 27558376

Created: 4 Apr 2025, 4:18 p.m.
Last Modified: 4 Apr 2025, 4:18 p.m.
Panel version: 1.211

Louise Daugherty (Genomics England Curator)

I don't know

Initial gene list (NGC_genelist-20190823_GREEN_dis_moi_forCuration_20200211.xlsx) collated by Dr Courtney French (University of Cambridge University Hospital NHS Foundation), Dr Karyn Megy (Clinical Feedback Lead, NIHR BioResource - Rare Diseases Study, University of Cambridge University Hospital NHS Foundation), Dr Alba Sanchis-Juan (NIHR BioResource - Rare Diseases Study, University of Cambridge University Hospital NHS Foundation) and Lucy Raymond (Professor of Medical Genetics and Neurodevelopment, University of Cambridge University Hospital NHS Foundation). Submitted to the PanelApp resource January 2020 on behalf of the Next Generation Children Project, Addenbrookes' Hospital, Cambridge. Gene Symbol submitted: HMBS; Recommended initial gene rating: Green List (high evidence); Phenotypes: Porphyria, acute intermittent, 176000 (3) | Porphyria, acute intermittent, nonerythroid variant, 176000 (3); Mode of inheritance: Autosomal dominant | Autosomal dominant
Created: 20 Feb 2020, 5:20 p.m. | Last Modified: 20 Feb 2020, 5:20 p.m.

Panel Version: 0.12

Created: 20 Feb 2020, 5:20 p.m.
Last Modified: 20 Feb 2020, 5:20 p.m.
Panel version: 0.12

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

Next Generation Children Project
Expert Review Green
Expert list

Phenotypes

Porphyria, acute intermittent, 176000
Porphyria, acute intermittent, nonerythroid variant, 176000

OMIM

609806

Clinvar variants

Variants in HMBS

Penetrance

None

Publications

30847515

Panels with this gene