Negative screening tests in classical galactosaemia caused by S135L homozygosity.
Affiliation
National Centre for Inherited Metabolic Disorders, Children's University Hospital, Temple St, Dublin 1, Ireland. ellen.crushell@cuh.ieIssue Date
2009-06MeSH
Amino Acid SubstitutionFalse Negative Reactions
Galactosemias
Homozygote
Humans
Infant
Infant, Newborn
Leucine
Male
Neonatal Screening
Serine
UDPglucose-Hexose-1-Phosphate Uridylyltransferase
Metadata
Show full item recordCitation
Negative screening tests in classical galactosaemia caused by S135L homozygosity. 2009, 32 (3):412-5 J. Inherit. Metab. Dis.Journal
Journal of inherited metabolic diseaseDOI
10.1007/s10545-009-1081-4PubMed ID
19418241Abstract
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 micromol/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.Item Type
ArticleLanguage
enISSN
1573-2665ae974a485f413a2113503eed53cd6c53
10.1007/s10545-009-1081-4