Screening for galactosemia: is there a place for it?

Abstract

Galactose is a hexose essential for production of energy, which has a prebiotic role and is essential for galactosylation of endogenous and exogenous proteins, ceramides, myelin sheath metabolism and others. The inability to metabolize galactose results in galactosemia. Galactosemia is an autosomal recessive disorder that affects newborns who are born asymptomatic, apparently well and healthy, then develop serious morbidity and mortality upon consuming milk that contains galactose. Those with galactosemia have a deficiency of an enzyme: classic galactosemia (type 1) results from severe deficiency of galactose-1-uridylyltransferase, while galactosemia type II results from galactokinase deficiency and type III results from galactose epimerase deficiency. Many countries include neonatal screening for galactosemia in their national newborn screening program; however, others do not, as the condition is rather rare, with an incidence of 1:30,000-1:100,000, and screening may be seen as not cost-effective and logistically demanding. Early detection and intervention by restricting galactose is not curative but is very rewarding, as it prevents deaths, mental retardation, liver cell failure, renal tubular acidosis and neurological sequelae, and may lead to resolution of cataract formation. Hence, national newborn screening for galactosemia prevents serious potential life-long suffering, morbidity and mortality. Recent advances in communication and biotechnology promise facilitation of logistics of neonatal screening, including improved cost-effectiveness.

Keywords: UDP galactose-4-epimerase; galactokinase; galactose-1-phosphate uridylyltransferase; galactosemia neonatal screening; galactosylation.

Figure 1

Galactose metabolism pathways; Leloir, oxidative and reductive galactose degradation pathways.

Figure 2

Role of galactose in vivo. Abbreviations: FSGS, focal segmental glomerulosclerosis; M. pneumoniae, Mycoplasma pneumoniae.

Figure 3

Complications of galactosemia. The spectrum of complications of galactosemia is dictated by the type of enzyme deficiency (GALT, GALK or GALE), residual enzyme activity, genotype, timing, amount and duration of exposure to galactose, endogenous galactose and galactitol production, intrauterine protection, institution of galactose-free versus galactose restriction and adult tolerance to galactose. Abbreviations: GALE, galactose-4-epimerase; GALK, galactokinase; GALT, galactose-1-uridylyltransferase.

Figure 4

Routes of exposure to galactose in vivo. (A) Milking of the cord. (B) Nursing galactose containing milk. (C) Endogenous synthesis of galactose in vivo.

Figure 5

World map of countries screening for galactosemia in neonates.