Clinicians use galactose-1-phosphate uridyl transferase to diagnose Galactose-1-phosphate uridyl transferase deficiency which is the most common cause of galactosemia and can be used a confirmation for abnormal state newborn screening.
Galactosemia is an autosomal recessive disorder that results from a deficiency of 1 of the three enzymes catalysing the conversion of galactose to glucose: galactose-1-phosphate uridyltransferase (GALT), galactokinase (GALK), and uridine diphosphate galactose-4-epimerase (GALE). GALT deficiency is the most common cause of galactosemia, and is often referred to as classic galactosemia. The complete or near complete deficiency of GALT enzyme is life threatening. If left untreated, complications include liver failure, sepsis, mental retardation, and death. Galactosemia is treated by a galactose-restricted diet, which allows for rapid recovery from the acute symptoms and a generally good prognosis. Despite adequate treatment from an early age, individuals with galactosemia remain at increased risk for developmental delays, speech problems, and abnormalities of motor function. Females with galactosemia are at increased risk for premature ovarian failure.
Infants affected by galactosaemia typically present with symptoms of lethargy, vomiting, diarrhoea, failure to thrive and jaundice.
Qualitative enzyme measurement is carried out by the referral lab. The diagnosis of galactosemia is established by follow-up quantitative measurement of GALT enzyme activity. If enzyme levels are indicative of carrier or affected status, molecular testing for common GALT mutations may be performed. This is important because heterozygotes require less severe dietary restrictions.
Duarte variant galactosemia (compound heterozygosity for the Duarte mutation, N314D, and a classic mutation) is generally associated with higher levels of enzyme activity (5% to 20%) than classic galactosemia (<5%); however, this may be indistinguishable by newborn screening assays. Typically, individuals with Duarte variant galactosemia have a milder phenotype but are also often treated with a low galactose diet during infancy. The LA variant, which consists of N314D and a second alteration in the gene, L218L, is associated with higher levels of GALT enzyme activity than the Duarte variant allele.
Galactose-1-phosphate accumulates in the erythrocytes of patients with galactosemia. The quantitative measurement of Galactose-1-phosphate is useful for monitoring compliance with dietary therapy. Galactose-1-phosphate is thought to be the causative factor for development of liver disease in these patients and because of this; patients should maintain low levels and be monitored on a regular basis. [This referral lab will also measure Galactose-1-phosphate].
If quantitative ref ranges are:-
Normal: 18 – 28 umol gal – 1 – P converted/hr/g Hb
Heterozygote: 8 – 14 umol gal – 1 – P converted/hr/g Hb
Whole blood – Lithium heparin (green top) or paediatric lithium heparin (with serum separator) for Qualitative Screen (usual request). Guthrie card can be used for quantitative analysis.
Take sample at beginning of week (If sample taken on Friday store in fridge over weekend – send on Monday.)If baby has had transfusion it is necessary to WAIT AT LEAST 6 WKS TO TAKE SAMPLE FOLLOWING TRANSFUSION.