Galactose intoxication and over-restriction in galactosemia may affect glycosylation pathways and cause multisystem effects. In this study, we describe an applied hydrophilic interaction chromatography ultra-performance liquid... more
Galactose intoxication and over-restriction in galactosemia may affect glycosylation pathways and cause multisystem effects. In this study, we describe an applied hydrophilic interaction chromatography ultra-performance liquid chromatography high-throughput method to analyze whole serum and extracted IgG N-glycans with measurement of agalactosylated (G0), monogalactosylated (G1), and digalactosylated (G2) structures as a quantitative measure of galactose incorporation. This was applied to nine children with severe galactosemia (genotype Q188R/Q188R) and one child with a milder variant (genotype S135L/S135L). The profiles were also compared with those obtained from three age-matched children with PMM2-CDG (congenital disorder of glycosylation type Ia) and nine pediatric control samples. We have observed that severe N-glycan assembly defects correct in the neonate following dietary restriction of galactose. However, treated adult galactosemia patients continue to exhibit ongoing N-glycan processing defects. We have now applied informative galactose incorporation ratios as a method of studying the presence of N-glycan processing defects in children with galactosemia. We identified N-glycan processing defects present in galactosemia children from an early age. For G0/G1, G0/G2, and (G0/G1)/G2 ratios, the difference noted between galactosemia patients and controls was found to be statistically significant (p = 0.002, 0.01, and 0.006, respectively).
Galactosemia is detected by newborn screening in New South Wales and managed by the metabolic team at the Children's Hospital at Westmead. Infants with the Duarte variant are not treated. Management is based on the Handbook for... more
Galactosemia is detected by newborn screening in New South Wales and managed by the metabolic team at the Children's Hospital at Westmead. Infants with the Duarte variant are not treated. Management is based on the Handbook for Galactosemia prepared in 1998. This handbook provides information for the family on the dietary management, inheritance and ovarian function. The major dietary sources of galactose are milk and milk products. Breastfeeding must be ceased and replaced with a soy formula. Once solid foods are commenced certain foods should be avoided. Other foods, which may contain some free galactose are recommended in limited quantities only. There is no restriction on other fruits and vegetables. An ongoing issue with dietary management is adequate nutrient intake, particularly of calcium. Intake of milk substitutes and calcium supplements is often inadequate.
To determine the incidence of galactosemia (GAL) in the Philippines and to determine whether newborn screening for GAL is cost-beneficial from a societal perspective, cost-benefit analysis was performed. Newborn screening for GAL was done... more
To determine the incidence of galactosemia (GAL) in the Philippines and to determine whether newborn screening for GAL is cost-beneficial from a societal perspective, cost-benefit analysis was performed. Newborn screening for GAL was done after the 24th hour of life using the Beutler test. Patients screened positive were recalled for confirmatory testing. Using incidence rates obtained from the different participating hospitals of the Philippine Newborn Screening Program (PNSP), the costs for the detection and treatment of GAL were compared to the expected benefits by preventing mental retardation, cataracts and other physical disabilities caused by the disorder that would lead to a loss of productivity for the individual. Sensitivity analyses for incidence and discount rates were also included. Of the 157,186 newborns screened by the PNSP since its inception in 1996, 8 screened positive results. Confirmatory testing of these patients showed that 2 had galactosemia. The incidence of...
Classic galactosemia is an autosomic recessive disorder that leads to increasegalactose 1 phosphate and galactitol intracellular levels; with clinical manifestations that arise from the ingestion of galactose from the diet but can be... more
Classic galactosemia is an autosomic recessive disorder that leads to increasegalactose 1 phosphate and galactitol intracellular levels; with clinical manifestations that arise from the ingestion of galactose from the diet but can be reverted when restricted. Yet about 90% of the patients develop neurological complications. Because of that we evaluate the impact of the diet on the generation of such complications, like the strict galactose restriction and the glycosilation impairment, galactosemia and social interactions as factors that influence neurodevelopment, oxidative stress secondary to galactosemia and its influence on neuroinflamation, epigenetics modifications secondary to the diet and the social interactions and other causes that can affect neurodevelopment on galactosemia.
Cerebral edema resulting in elevated intracranial pressure is a well-known complication of galactosemia. Lumbar puncture was performed for the diagnosis of clinically suspected bacterial meningitis. Herniation of cerebral tissue through... more
Cerebral edema resulting in elevated intracranial pressure is a well-known complication of galactosemia. Lumbar puncture was performed for the diagnosis of clinically suspected bacterial meningitis. Herniation of cerebral tissue through the foramen magnum ...
