The GALT enzyme activity in erythrocytes from 160 individuals, in which 135 with classic, clinical variant or biochemical variant galactosemia, was quantified by LC-MS/MS.
Galactosemia Proteins Database 2.0 is a Web-accessible resource collecting information about the structural and functional effects of the known variations associated to the three different enzymes of the Leloir pathway encoded by the genes GALT, GALE, and GALK1 and involved in the different forms of the genetic disease globally called "galactosemia."
Our findings suggest that GALT activity cannot be the sole pathogenic factor accounting for galactosemia long-term complications, and that some organs/cells might have a greater susceptibility to galactose toxicity.Anat Rec, 300:1570-1575, 2017.
This study expands the mutation spectrum in GALT gene and reinforces the importance of early diagnosis and introduction of dietary treatment, what is possible with the introduction of Galactosemia in neonatal screening programs.
Kalckar's work established that defects in galactose 1-phosphate uridylyltransferase (GALT) were responsible for the majority of cases of galactosemia.
Our results expand the mutation spectrum in GALT gene and the list of GALT variations analyzed at the structural level, providing new data to assess the pathophysiology of galactosemia.
The functionally neutral N314D variation in the GALT gene is associated with Duarte galactosemia and is widespread among various worldwide populations.
In classic galactosemia, the erythrocyte GALT enzyme activity is absent or markedly reduced, the blood galactose and erythrocyte galactose-1-phosphate levels are markedly elevated, and the patient is at risk to develop potentially lethal E. coli sepsis, as well as the long-term diet-independent complications of galactosemia.
The study highlighted the heterogeneity of classical galactosemia in the Indian population and also emphasizes the importance of GALT gene analysis in diagnosis of galactosemia.
In the very first instance of its kind from India, the authors report the presence of three different galatose-1-phosphate uridyl transferase (GALT) gene mutations, associated with galactosemia, in a single Indian family.
Classical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene.
Patients with Duarte galactosemia demonstrate reduced GALT activity and carry one profoundly impaired GALT allele (G) along with a second, partially impaired GALT allele (Duarte-2, D2).
Hereditary galactosemia is a biochemical genetic disease due to a deficiency of galactose-1-phosphate uridyltransferase (GALT) enzyme activity (OMIM 606999).
In the present study, we report molecular analysis of 14 unrelated Iranian galactosemia children with reduced or without GALT activity using PCR-RFLP and SSCP-Sequencing methods.