Upon being fed with milk, newborns develop a
variable combination of the following symptoms: lethargy, irritability,
hypotonia, vomiting, hypoglycemia, seizures, failure to thrive, jaundice,
hepatomegaly, liver dysfunction (including coagulopathy with bleeding),
ascites, and splenomegaly. Cataracts are typical and already present in the
neonatal period. It is essential to diagnose galactosemia early, otherwise
hardly reversible or even irreversible and severe damage to brain (mental
retardation), liver (macronodular cirrhosis, portal hypertension,
hypersplenism), and eyes (cataract) may be established. Transfer of
galactose from maternal into fetal circulation can lead to toxic changes in
utero. Although not common on a normal diet, hypoglycemic episodes can occur
after ingestion of galactose and are caused by either elevated levels of
galactose-1-phosphate, which can inhibit the conversion of glycogen to
glucose, or increased insulin release. A higher risk of Escherichia coli sepsis in
galactosemia patients has been reported. In fact, galactosemia should be
ruled out in neonates with sepsis from this pathogen. Renal tubular
dysfunction and albuminuria with later transition into generalized amino
aciduria has been described. Hypergonadotropic hypogonadism is a common
finding. The condition should be suspected in males presenting with small
testes. Females with primary ovarian failure and primary (or secondary)
amenorrhea but normal development and even uncomplicated pregnancy have been
described. Short stature, ataxia, tremor, EEG abnormalities, and
difficulties with learning and speech (verbal dyspraxia) are other features
of galactosemia. Treatment consists of elimination of galactose from the
diet as soon as the diagnosis is made. No specific drug therapy exists.
Although a galactose-free diet protects the body from the severe toxic
effects of galactose-1-phosphate, it cannot prevent all the long-term
complications (e.g., hypogonadism, cerebellar signs). These long-term
complications have been suggested to be caused by “self-intoxication” of
the body with galactose, because UDP-galactose can be synthesized from
glucose through the enzymes UDP-glucose-pyrophosphorylase and
UDP-galactose-4-epimerase, which both are part of the Leloir pathway. Other
researchers believe that cerebral complications are the result of in utero
exposition to high levels of galactose-1-phosphate.