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A life-threatening metabolic disease with onset in the neonatal period. Infants usually develop feeding difficulties, lethargy, and severe liver disease.
ORPHA:79239Classification level: Disorder
- GALT deficiency
- Galactose-1-phosphate uridyltransferase deficiency
- Galactosemia type 1
- Prevalence: Unknown
- Inheritance: Autosomal recessive
- Age of onset: Infancy, Neonatal
- ICD-10: E74.2
- OMIM: 230400
- UMLS: C0268151
- MeSH: -
- GARD: -
- MedDRA: -
Global prevalence is unknown but estimated annual incidence has been reported to be between 1/40,000 and 1/60,000 in Western countries. The disorder appears to be more common in the Caucasian population than in other ethnic groups but figures in other populations may be underestimated. Males and females are equally affected.
When ingesting breast milk or lactose-containing formula, infants develop feeding problems, failure to thrive, and signs of liver damage (jaundice, bleeding tendency, hypoglycemia). In the absence of appropriate treatment (galactose restriction), sepsis (E-coli) and neonatal death may occur. Despite adequate treatment, long-term complications appear including cognitive impairments, motor deficits, ovarian dysfunction with reduced fertility in women and diminished bone density. Male fertility has not yet been thoroughly studied.
Classic galactosemia is caused by mutations in the GALT (9p13) gene encoding the galactose-1-phosphate uridyltransferase enzyme. Mutations that severely impair enzyme activity result in the classic galactosemia phenotype. The so-called variants are mutations associated with higher residual enzyme activity resulting in milder or no features of galactosemia such as the Duarte variant (GALT gene mutation).
In many countries, infants are routinely screened for galactosemia at birth. When neonatal screening is not performed, diagnosis is based on the clinical picture. Diagnosis can be confirmed by assay of the relevant metabolites, enzyme activity and GALT gene mutational analysis.
Differential diagnoses include galactose epimerase deficiency and other diseases causing acute liver disease in the neonate.
Prenatal testing is usually performed via gene mutation analysis by chorionic villus sampling. In at-risk relatives, testing is also possible to search for the mutation when already identified in a family.
Galactosemia follows an autosomal recessive pattern of inheritance. Parents of an affected child have a 25% risk of having affected children in subsequent pregnancies.
Management and treatment
Treatment is based primarily on galactose restriction in the diet. Infants should be fed with soy formula or other lactose-free formula. Patients are advised to follow a lifelong diet. To prevent a diminished bone mass, calcium, vitamin D and vitamin K supplements are recommended if dietary intake does not meet the recommended daily allowance. Monitoring of cognitive and motor development, gonadal function and bone mass is mandatory. Eye examinations are recommended in case of neonatal cataracts or in case of poor dietary compliance. Despite dietary treatment long-term complications occur.
Prognosis is dependent on age of diagnosis, disease severity and compliance with dietary restrictions, which affects the onset and course of secondary complications.