Miscellaneous Metabolic Disorders
Gene: GALM
8 unrelated cases with galactosaemia and supporting in vitro assays. GALM deficiency is an inborn error of galactose metabolism.
Sources: NHS GMSCreated: 4 Feb 2021, 4:08 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Galactosemia IV MIM#618881; Disorders of galactose metabolism
Publications
Variants in this GENE are reported as part of current diagnostic practice
Homozygous and compound heterozygous variants (missense, nonsense and frameshift) found in 8 Japanese patients from unrelated families with unexplained galactosaemia. (No variants in GALT, GALK1, and GALE). This is therefore type IV galactosaemia.
In vitro expression analysis and enzyme activity assay of the patients’ peripheral blood mononuclear cells showed total lack of or compromised expression of GALM protein. Loss-of-function mechanism. One homozygote for one of these variants p.(Gly142Arg) in gnomAD (African population). (Wada, Y. et al 2019; PMID: 30451973)
In vitro expression assay and an enzyme activity assay of 67 GALM variants, taken from ExAc database (missense, nonsense, frameshift and splice). 30 variants concluded to be pathogenic due to no protein expression or faint expression. 5 variants with mildly lower levels were determined as likely pathogenic. All concluded to be loss-of-function mechanism. Incidence of galactosaemia by GALM deficiency is comparable to that of other galactosaemias. Carrier frequency and incidence was estimated for different populations. (Iwasawa, S. et al. (2019); PMID: 30910422)
Sources: LiteratureCreated: 24 Apr 2020, 8:29 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
galactosaemia; type IV galactosaemia
Publications
Gene: galm has been classified as Green List (High Evidence).
Gene: galm has been classified as Green List (High Evidence).
gene: GALM was added gene: GALM was added to Miscellaneous Metabolic Disorders. Sources: NHS GMS Mode of inheritance for gene: GALM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GALM were set to 30451973; 30910422 Phenotypes for gene: GALM were set to Galactosemia IV MIM#618881; Disorders of galactose metabolism Review for gene: GALM was set to GREEN gene: GALM was marked as current diagnostic