Uridine Diphosphate Galactose Epimerase Deficiency

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