Negative screening tests in classical galactosaemia caused by S135L homozygosity.

Hdl Handle:
http://hdl.handle.net/10147/189712
Title:
Negative screening tests in classical galactosaemia caused by S135L homozygosity.
Authors:
Crushell, E; Chukwu, J; Mayne, P; Blatny, J; Treacy, E P
Affiliation:
National Centre for Inherited Metabolic Disorders, Children's University Hospital, Temple St, Dublin 1, Ireland. ellen.crushell@cuh.ie
Citation:
Negative screening tests in classical galactosaemia caused by S135L homozygosity. 2009, 32 (3):412-5 J. Inherit. Metab. Dis.
Journal:
Journal of inherited metabolic disease
Issue Date:
Jun-2009
URI:
http://hdl.handle.net/10147/189712
DOI:
10.1007/s10545-009-1081-4
PubMed ID:
19418241
Abstract:
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:
Article
Language:
en
MeSH:
Amino Acid Substitution; False Negative Reactions; Galactosemias; Homozygote; Humans; Infant; Infant, Newborn; Leucine; Male; Neonatal Screening; Serine; UDPglucose-Hexose-1-Phosphate Uridylyltransferase
ISSN:
1573-2665

Full metadata record

DC FieldValue Language
dc.contributor.authorCrushell, Een
dc.contributor.authorChukwu, Jen
dc.contributor.authorMayne, Pen
dc.contributor.authorBlatny, Jen
dc.contributor.authorTreacy, E Pen
dc.date.accessioned2011-11-15T16:34:37Z-
dc.date.available2011-11-15T16:34:37Z-
dc.date.issued2009-06-
dc.identifier.citationNegative screening tests in classical galactosaemia caused by S135L homozygosity. 2009, 32 (3):412-5 J. Inherit. Metab. Dis.en
dc.identifier.issn1573-2665-
dc.identifier.pmid19418241-
dc.identifier.doi10.1007/s10545-009-1081-4-
dc.identifier.urihttp://hdl.handle.net/10147/189712-
dc.description.abstractClassical 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.-
dc.language.isoenen
dc.subject.meshAmino Acid Substitution-
dc.subject.meshFalse Negative Reactions-
dc.subject.meshGalactosemias-
dc.subject.meshHomozygote-
dc.subject.meshHumans-
dc.subject.meshInfant-
dc.subject.meshInfant, Newborn-
dc.subject.meshLeucine-
dc.subject.meshMale-
dc.subject.meshNeonatal Screening-
dc.subject.meshSerine-
dc.subject.meshUDPglucose-Hexose-1-Phosphate Uridylyltransferase-
dc.titleNegative screening tests in classical galactosaemia caused by S135L homozygosity.en
dc.typeArticleen
dc.contributor.departmentNational Centre for Inherited Metabolic Disorders, Children's University Hospital, Temple St, Dublin 1, Ireland. ellen.crushell@cuh.ieen
dc.identifier.journalJournal of inherited metabolic diseaseen
dc.description.provinceLeinster-

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