From the Guidelines
Genetic testing is not required for the initial diagnosis of galactosemia. The diagnosis can be established through biochemical testing, which includes measuring galactose-1-phosphate uridyltransferase (GALT) enzyme activity in red blood cells and detecting elevated galactose metabolites in blood or urine 1. Newborn screening programs typically test for galactosemia by measuring GALT activity or total galactose levels in dried blood spots. When these tests show abnormal results, follow-up confirmatory testing is performed. While genetic testing is not mandatory for diagnosis, it is valuable for confirming the specific genetic variant causing the condition, determining carrier status in family members, enabling prenatal diagnosis in future pregnancies, and distinguishing between classic galactosemia and variant forms like Duarte galactosemia 1. The most common genetic mutations occur in the GALT gene, though mutations in GALK1 and GALE genes can cause other forms of galactosemia.
Some key points to consider in the diagnosis of galactosemia include:
- Newborn screening programs can detect galactosemia by measuring GALT activity or total galactose levels in dried blood spots 1
- Biochemical testing, including measuring GALT enzyme activity in red blood cells and detecting elevated galactose metabolites in blood or urine, is sufficient for initiating appropriate management
- Genetic testing can provide additional information, such as confirming the specific genetic variant causing the condition and determining carrier status in family members
- Treatment involves a galactose-restricted diet, regardless of whether genetic testing is performed 1
In terms of the role of genetic testing in the diagnosis of galactosemia, it is important to note that:
- Molecular testing can distinguish between different allele combinations, such as heterozygotes for classic galactosemia, Duarte variant homozygotes, and LA variant galactosemia 1
- Full-gene sequencing followed by gene-targeted deletion/duplication testing can be used to identify pathogenic variants in the GALT, GALK1, and GALE genes 1
- Genetic testing can be used to confirm or exclude GALK or GALE deficiency in cases where the newborn screen is abnormal 1
From the Research
Genetic Testing for Galactosemia
- Genetic testing is essential for diagnosing certain types of galactosemia, such as GALM deficiency, as no biochemical diagnosis method has been established 2.
- Galactosemia is an autosomal recessive genetic disease that can be diagnosed at birth with newborn screening by assessing the level of galactose and the GALT enzyme activity 3.
- The diagnosis of galactosemia can be made through the measurement of plasma galactose and galactitol concentration, as well as the assessment of GALT enzyme activity 4.
- Reliable assays to measure the activity of the Leloir pathway enzymes, including galactose-1-phosphate uridyltransferase, are crucial for understanding the pathophysiological mechanisms involved in galactosemia and developing novel therapies 5.
- The mechanisms of acute and long-term complications in galactosemia are still being discussed, and genetic testing can help identify allelic variants associated with the disease 6.
Types of Galactosemia
- There are different types of galactosemia, including type I, II, and III, which are characterized by deficiencies in the enzymes GALT, GALK1, or GALE, respectively 2.
- Type IV galactosemia is a novel type of galactosemia caused by biallelic GALM mutations, and genetic diagnosis is indispensable for diagnosing this condition 2.