Miscellaneous Metabolic Disorders

Gene: GALM

Green List (high evidence)

8 unrelated cases with galactosaemia and supporting in vitro assays. GALM deficiency is an inborn error of galactose metabolism.
Sources: NHS GMS

Created: 4 Feb 2021, 4:08 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Galactosemia IV MIM#618881; Disorders of galactose metabolism

Publications

• 30451973
• 30910422

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

Green List (high evidence)

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: Literature

Created: 24 Apr 2020, 8:29 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
galactosaemia; type IV galactosaemia

Publications

• PMID: 30451973
• 30910422