Skip to Main Content

At a glance

A disorder of galactose metabolism characterized by a deficiency of uridylyl diphosphogalactose-4-epimerase activity resulting in benign asymptomatic form (deficiency in blood cells only) and severe forms with hepatic failure, ☞Fanconi-Bickler Syndrome, and neurological impairment.

Synonyms

Galactose Epimerase Deficiency; Gale Deficiency; Galactosemia III; UDP-Galactose-4-Epimerase Deficiency.

Incidence

Very rare medical condition presenting with great variability among populations. A severe form has been described in Japan with an incidence of 1:23,000 live births, whereas it is limited to few cases in England. Benign forms have been reported in African-Americans with a frequency of 1:6,200 live births and 1:64,800 in non-black Americans.

Genetic inheritance

Autosomal recessive.

Pathophysiology

Uridylyl diphosphogalactose-4-epimerase assists in the conversion of galactose-1-phosphate to glucose-1-phosphate by catalyzing the conversion of uridine diphosphate (UDP)-glucose to UDP-galactose. The disease is caused by mutation in the UDP-galactose-4-epimerase gene (GALE) located at 1p36-p35.

Diagnosis

Generally made by the discovery of elevated galactose sugars in newborn screening programs, but associated with a normal level of galactose-1-phosphate uridylyltransferase. Benign forms are associated with a galactose epimerase deficiency in red blood cells and leukocytes, whereas the epimerase activity in the liver, activated lymphocytes, and cultured skin fibroblasts is normal.

Clinical aspects

Identical to the classical form of galactosemia involving gastrointestinal (vomiting, feeding difficulties, failure to thrive, jaundice, hepatomegaly, hypoglycemia, ascites, splenomegaly, hepatic cirrhosis) and central nervous system (sensorineural deafness, lethargy, irritability, hypotonia, mental retardation, language, cognitive, and developmental delay). ☞Fanconi-Bickler Syndrome (vomiting, dehydration, weakness, unexplained fever, anorexia, constipation, polydipsia, and polyuria). Cataract can also be present.

Precautions before anesthesia

Evaluate hepatic and renal functions (laboratory investigation, clinical, and echography) and neurological function (clinical, EEG, CT scan).

Anesthetic considerations

Few specific considerations; implications are related to renal and cardiac dysfunction.

Pharmacological implications

Perioperative fluid regimen and anesthetic drugs should be adapted in consideration for hepatic and renal functions. Aminoglycosides should be used carefully because of deafness and potential renal dysfunction. Consider interaction between antiepileptic treatment and anesthetic drugs.

References

+
Berry  GT: Galactosemia: When is it a newborn screening emergency? Mol Genet Metab 106:7, 2012.  [PubMed: 22483615]
+
Maceratesi  P, Daude  N, Dallapiccola  B,  et al: Human UDP-galactose 4’ epimerase (GALE) gene and identification of five missense mutations in patients with epimerase-deficiency galactosemia. Mol Genet Metab 63:26, 1998.  [PubMed: 9538513]
+
Timson  DJ: The molecular basis of galactosemia - Past, present and future. Gene 589:133, 2016.  [PubMed: 26143117]
+
Wohlers  TM, Christacos  NC, Harreman  MT,  et al: Identification and characterization of a mutation, in the human UDP-galactose-4-epimerase gene, associated with ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.