Rare diseases
Conventional galactosemia in newborns occurs in about 1 in 60,000 births. However, prevalence varies geographically, fluctuating from 1/40,000 in Europe to 1/1,000,000 in Japan.
Galactosemia is defined by an alteration in the metabolism of galactose, caused by a deficient activity of one of the three enzymes involved in its metabolism. Conventional galactosemia, due to complete galactose-1-phosphate uridyl transferase (GALT) deficiency, is the most common and produces the most severe galactosemia symptoms in infants. Two other much rarer forms of galactosemia exist, galactokinase (GALK) and UDP-galactose epimerase (GALE) deficiencies. The genes involved are GALT, GALK1 and GALE, respectively.
Conventional galactosemia is a severe disease that begins when a person swallows milk through eating disorders, lethargy, growth failure, and severe liver and kidney damage. Neonatal sepsis may also occur. A cataract appears within days or weeks. In the longer term, learning difficulties and ovarian failure in girls may occur. Partial deficits, due to a relatively common GALT mutation, called “Duarte”, have a much less severe clinical presentation, which may even remain asymptomatic.
GALK deficiency is responsible for isolated cataracts. GALE deficiency manifests itself as a variable clinical presentation resembling classical galactosemia.
The neonatal screening programs for galactosemia are traditionally based on a total galactose assay and/or GALT activity.
The diagnosis of classical galactosemia (including partial deficiencies) is then confirmed by a galactosemia lab test to detect a high concentration of erythrocyte galactose-1-phosphatase, urinary galactitol and the identification of bi-allelic pathogenic variants in the GALT gene.
The main objective of long-term treatment of classical galactosemia is to minimize the dietary intake of galactose. This dietary management protects against liver and renal complications, as well as cataracts. However, it does not prevent learning difficulties and hormone disorders from appearing. A follow-up is required and focuses on psychomotor development and gonadal function.
The erythrocyte galactose-1-phosphate assay helps ensure patients adhere to their diet. Partial GALT deficiencies will be treated based on residual enzymatic activity, and erythrocyte galactose-1-phosphate concentration.
Galactosemia is inherited in an autosomal recessive manner, regardless of the form considered.
The NEONATAL Total Galactose Screening Assay is an enzymatic test used to quantify total galactose (galactose and galactose-1-phosphate) as part of neonatal screening blood test for galactosemia. This test is performed based on dried blood samples taken on 903® and 226 type blotted paper.