Galactosemia is an inborn error of galactose metabolism, caused by an abnormality in the conversion of galactose and uridine diphosphoglucose to glucose-1-phosphate and uridine diphosphogalactose through the action of 3 sequential enzymes: galactokinase (GALK), galactose- 1-phosphate uridyltransferase (GALT), and uridine phosphogalactose 4-epimerase (GALE). The advent of newborn screening brought hope with early diagnosis and prompt treatment. Newborn screening advocates have pushed for inclusion of galactosemia in the newborn screening panel. However, reports of complications despite early treatment have questioned the merits of universal screening. This paper presents issues in favour and against universal newborn screening for galactosemia.
Galactosemias ; diagnosis ; Humans ; Infant, Newborn ; Neonatal Screening ; standards

BACKGROUNDSotos syndrome is an overgrowth syndrome with characteristic facial gestalt and mental retardation of variable severity. Haploinsufficiency of the NSD1 gene has been implicated as the major cause of Sotos syndrome, with a predominance of microdeletions reported in Japanese patients. This study was conducted to investigate into the spectrum of NSD1 gene mutations in southern Chinese patients with Sotos syndrome.

METHODSThirty-six Chinese patients with Sotos syndrome and two patients with Weaver syndrome were subject to molecular testing.

RESULTSNSD1 gene mutations were detected in 26 (72%) Sotos patients. Microdeletion was found in only 3 patients, while the other 23 had point mutations (6 frameshift, 8 nonsense, 2 spice site, and 7 missense). Of these, 19 mutations were never reported. NSD1 gene mutations were not found in the two patients with Weaver syndrome.

CONCLUSIONSMost cases of Sotos syndrome are caused by NSD1 gene defects, but the spectrum of mutations is different from that of Japanese patients. Genotype-phenotype correlation showed that patients with microdeletions might be more prone to congenital heart disease but less likely to have somatic overgrowth. The two patients with Weaver syndrome were not found to have NSD1 gene mutations, but the number was too small for any conclusion to be drawn.

Abnormalities, Multiple ; genetics ; Brain ; abnormalities ; Child, Preschool ; Craniofacial Abnormalities ; genetics ; Developmental Disabilities ; genetics ; Gene Deletion ; Growth Disorders ; genetics ; Humans ; Infant ; Intracellular Signaling Peptides and Proteins ; genetics ; Mutation ; Nuclear Proteins ; genetics ; Syndrome