classic galactosemia

Classic galactosemia is a severe metabolic disorder that presents in the neonatal period and affects the body’s ability to properly process galactose. Pathogenic variants in the GALT gene result in deficient enzyme activity, leading to the accumulation of toxic metabolites. Affected infants typically display feeding difficulties, lethargy, and signs of liver dysfunction. Prevalence estimates remain uncertain, and the frequency of the condition is not clearly established.

Infants with classic galactosemia display a range of clinical features that include generalized hypotonia, increased levels of galactitol in plasma, and bilateral tonic-clonic seizures, all of which are consistently observed. They also experience jaundice, vomiting, and feeding difficulties in the early period of life, with delayed speech and language development emerging later. Additional findings such as reduced erythrocyte galactose-1-phosphate uridylyltransferase activity are always present, while cataracts and elevated liver enzymes occur in a subset of individuals. Not all individuals experience every feature, and severity varies considerably.

Classic galactosemia is caused by pathogenic variants in the GALT gene, which encodes an enzyme essential for the metabolism of galactose. When this enzyme does not function properly, toxic substances build up in the body, leading to the clinical manifestations observed. The condition is inherited in an autosomal recessive manner, meaning that an individual must inherit a variant from both parents to be affected. Families are encouraged to seek genetic counseling to fully understand recurrence risks and the implications for other family members.

Currently, management of classic galactosemia focuses on supportive care and symptom management. Treatment is highly individualized and typically involves a multidisciplinary team that addresses liver dysfunction, feeding difficulties, and developmental delays. While no treatments have been specifically approved for classic galactosemia, investigational therapies are under investigation, and clinical trials are exploring potential new approaches. Genetic counseling is recommended to help families understand treatment options and inheritance considerations, and patients should discuss all available strategies with their healthcare team.

Outcomes for classic galactosemia are variable and depend on the severity of enzyme deficiency and the timeliness of supportive interventions. With current standards of care, many individuals are managed into later childhood, although the condition represents a lifelong challenge. Severity and symptoms vary widely between individuals, and outcomes may improve as modern treatment approaches evolve. Patients and families are encouraged to connect with genetic counselors or specialists to explore ongoing care strategies and support services. Outcomes described in medical literature continue to evolve as standards of care improve.

Clinical trials are underway exploring new treatment approaches for classic galactosemia. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.