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 syndrome, and neurological impairment.
Galactose Epimerase Deficiency; Gale Deficiency;
Galactosemia III. UDP-Galactose-4-Epimerase Deficiency.
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.
Uridylyl diphosphogalactose-4-epimerase assists in
the conversion of galactose-1-phosphate to glucose1-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.
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.
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 syndrome (vomiting,
dehydration, weakness, unexplained fever, anorexia, constipation,
polydipsia, and polyuria). Cataract can also be present.
Evaluate hepatic and renal functions
(laboratory investigation, clinical and echography) and neurological
function (clinical, EEG, CT scan).
Few specific considerations;
implications are related to renal and cardiac dysfunction.
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.
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
Wohlers TM, Christacos NC, Harreman MT, et al: Identification and
characterization of a mutation, in the human UDP-galactose-4-epimerase gene,
associated with generalized epimerase-deficiency galactosemia. Am J Hum Genet