November 2011
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Classical galactosemia – Latest Evidence
This part of the document will be changed in the first revision, in which the level of evidence will
be displayed throughout this care pathway.
Classical galactosemia
Classical galactosemia (McKusick 230400) is an autosomal recessive disorder of galactose
metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridyltransferase
(
GALT; EC 2.7.712).
1
The prevalence in the Western Europe is estimated between 1: 23.500 and 1:
44.0000.
2,3
Most patients present in the neonatal period, after ingestion of galactose, with feeding
difficulties, liver failure, renal tubular dysfunction, (E. Coli) sepsis and cataract.
Currently most countries have included galactosemia in the newborn screening programs. The
majority of patients are discovered by this screening, although most of these patients already are
admitted to the hospital due to illness. The diagnosis classical galactosemia is made by
demonstrating a deficient GALT enzyme activity (usually < 1%) and confirmed with mutation
analysis of the GALT gen.
Patients with Duarte galactosemia manifest about 25% of wild-type GALT activity. They are
frequently detected in newborn-screening. Since clinical and developmental outcomes in Duarte
galactosemia are good regardless of any diet changes, there is no need for treatment or follow-
up.
4,5
Treatment
Treatment consists of a life-long lactose-free, strict galactose restricted diet without limitations in
intake in fruit and vegetables.
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There is a strong contrast between the exogenous intake of galactose in the galactose-restricted
diet (average intake < 60 mg per day) and endogenous production of galactose in adult patients
(
around 1000 mg per day). Full dietary relaxation should probably be strongly discouraged until the
pathophysiology behind the long-term complications has been elucidated.
2
Complications
In spite of the galactose-restricted diet, long-term complications such as cognitive impairments,
speech and language abnormalities, motor problems and hypergonadotropic hypogonadism are
frequently seen. It has been suggested that long term complications may result from endogenous
galactose synthesis. Furthermore, abnormalities in various glycoproteins have been reported,
abnormal glycosylation may also be involved.
1
Cognition
Despite a strict galactose-free diet, cognitive functioning is often below average. The mean overall
scores for verbal and performance IQ, memory, and executive functions are in the low average
range.
7
In the Netherlands, more than 50% of patients need special education in primary
education.
8
Until now, there is no conclusive evidence whether there is a negative correlation
between age and cognitive functioning.
7,9
Speech disorders and language disorders
Children with classic galactosemia are at risk for motor speech disorders (MSD) resulting from
disruptions in motor planning and programming (Childhood Apraxia of Speech: CAS) or, less
frequently, motor execution (dysarthria).They are also at risk for language impairments (i.e.
synthax) independently from motor disorders.
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