Galactosemia: when is it a newborn screening emergency?

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Classic galactosemia is an autosomal recessive metabolic disorder caused by severe deficiency of galactose-1-phosphate uridyltransferase (GALT).
• Lactose consumption in neonates with GALT deficiency can lead to a life-threatening, multi-organ disease process.
• Newborn screening (NBS) has reduced the incidence of severely ill infants but necessitates differentiating classic from variant forms of GALT deficiency.

Purpose of the Study:

• To present a classification scheme for GALT deficiency to aid clinicians in making correct therapeutic decisions following positive NBS results.
• To differentiate between classic, clinical variant, and biochemical variant galactosemia for appropriate patient management and parental counseling.

Main Methods:

• Review of GALT gene mutations and their correlation with clinical phenotypes.
• Classification of GALT deficiency into three forms: classic, clinical variant, and biochemical variant, based on genotype and enzyme activity.
• Analysis of erythrocyte GALT enzyme activity, blood galactose, and erythrocyte galactose-1-phosphate levels in different GALT deficiency forms.

Main Results:

• Classic galactosemia is characterized by absent/markedly reduced GALT activity, elevated blood galactose and erythrocyte galactose-1-phosphate, posing a risk of E. coli sepsis and long-term complications.
• Clinical variant galactosemia requires treatment but does not typically result in neonatal E. coli sepsis.
• Biochemical variant galactosemia and false positives are common findings in NBS, highlighting the need for accurate differentiation.

Conclusions:

• A clear classification of GALT deficiency is crucial for timely and appropriate management of infants identified through NBS.
• Immediate initiation of a lactose-restricted diet is recommended for infants suspected of having galactosemia, even based on clinical findings alone.
• Accurate diagnosis based on genotype and biochemical markers ensures optimal outcomes and informative genetic counseling for families.