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Negative screening tests in classical galactosaemia caused by S135L homozygosity
E Crushell1, J Chukwu, P Mayne
1National Centre for Inherited Metabolic Disorders, Children's University Hospital, Temple St, Dublin 1, Ireland. ellen.crushell@cuh.ie
Journal of Inherited Metabolic Disease
|May 7, 2009
Summary
Classical galactosaemia, a genetic disorder, can be missed by standard newborn screening. Early GALT enzyme analysis is crucial for accurate diagnosis, especially in infants with developmental delays and physical abnormalities.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Classical galactosaemia is a common genetic disorder in Ireland, often screened via bacterial inhibition assay (BIA).
- Newborn screening typically uses BIA for free galactose, with Beutler assay reserved for high-risk infants.
Observation:
- A 16-month-old boy presented with developmental delay, failure to thrive, microcephaly, hepatomegaly, and cataracts.
- Initial newborn screening and urinary tests were negative, despite a diet of cow's milk and cereal.
- Red blood cell galactose-1-phosphate uridyltransferase (GALT) activity was absent, confirming classical galactosaemia.
Findings:
- Mutation analysis revealed S135L homozygosity in the GALT gene.
- This genotype presents with absent red cell GALT activity but residual activity in other tissues, potentially explaining false-negative screening.
- Standard screening methods like urinary reducing substances and BIA are unreliable for S135L homozygous galactosaemia.
Implications:
- Galactosaemia should be considered in children with poor growth, hepatomegaly, developmental delay, and cataracts.
- GALT enzyme analysis should be a primary diagnostic test for suspected galactosaemia.
- This case highlights the limitations of non-enzymatic screening in specific genetic variants of galactosaemia.
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