Journal of Inherited Metabolic Disease

, Volume 32, Issue 3, pp 412–415 | Cite as

Negative screening tests in classical galactosaemia caused by S135L homozygosity

  • E. Crushell
  • J. Chukwu
  • P. Mayne
  • J. Blatny
  • E. P. Treacy
Original Article


Classical galactosaemia is relatively common in Ireland due to a high carrier rate of the Q188R GALT mutation. It is screened for using a bacterial inhibition assay (BIA) for free galactose. A Beutler assay on day one of life is performed only in high risk cases (infants of the Traveller community and relatives of known cases). A 16-month-old Irish-born boy of Nigerian origin was referred for investigation of developmental delay, and failure to thrive. He had oral aversion to solids and his diet consisted of cow’s milk and milk-based cereal mixes. He was found to have microcephaly, weight <2nd percentile, hepatomegaly and bilateral cataracts. Coagulation screen was normal and transaminases were slightly elevated. His original newborn screen was reviewed and confirmed to have been negative; urinary reducing substances on three separate occasions were negative. Beutler assay demonstrated “absent” red cell galactose-1-phosphate uridyltransferase (GALT) activity. GALT enzyme activity was <0.5 gsubs/h per gHb confirming classical galactosaemia. Gal-1-P was elevated at 1.88 μmol/gHb. Mutation analysis of the GALT gene revealed S135L homozygosity. S135L/S135L galactosaemia is associated with absent red cell GALT activity but with approximately 10% activity in other tissues such as the liver and intestines, probably explaining the negative screening tests and the somewhat milder phenotype associated with this genotype. The patient was commenced on galactose-restricted diet; on follow-up at 2 years of age, growth had normalized but there was global developmental delay. In conclusion, galactosaemia must be considered in children who present with poor growth, hepatomegaly, developmental delay and cataracts and GALT enzyme analysis should be a first line test in such cases. Non-enzymatic screening methods such as urinary reducing substances and BIA for free galactose are not reliable in S135L homozygous galactosaemia.


Newborn Screen GALT Activity G6PD Enzyme Classical Galactosaemia High Carrier Rate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



bacterial inhibition assay


congenital disorders of glycosylation


glucose-6-phosphate dehydrogenase


glucose-6-phosphate dehydrogenase deficiency


galactose-1-phosphate uridyltransferase


mean corpuscular haemoglobin


mean corpuscular volume


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Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • E. Crushell
    • 1
  • J. Chukwu
    • 1
  • P. Mayne
    • 2
  • J. Blatny
    • 3
  • E. P. Treacy
    • 1
  1. 1.National Centre for Inherited Metabolic DisordersChildren’s University HospitalDublin 1Ireland
  2. 2.Department of Chemical PathologyChildren’s University HospitalDublin 1Ireland
  3. 3.Department of HaematologyChildren’s University HospitalDublin 1Ireland

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