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Negative screening tests in classical galactosaemia caused by S135L homozygosity.
J Inherit Metab Dis. 2009 Jun; 32(3):412-5.JI

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.

Authors+Show Affiliations

National Centre for Inherited Metabolic Disorders, Children's University Hospital, Temple St, Dublin 1, Ireland. ellen.crushell@cuh.ieNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

19418241

Citation

Crushell, E, et al. "Negative Screening Tests in Classical Galactosaemia Caused By S135L Homozygosity." Journal of Inherited Metabolic Disease, vol. 32, no. 3, 2009, pp. 412-5.
Crushell E, Chukwu J, Mayne P, et al. Negative screening tests in classical galactosaemia caused by S135L homozygosity. J Inherit Metab Dis. 2009;32(3):412-5.
Crushell, E., Chukwu, J., Mayne, P., Blatny, J., & Treacy, E. P. (2009). Negative screening tests in classical galactosaemia caused by S135L homozygosity. Journal of Inherited Metabolic Disease, 32(3), 412-5. https://doi.org/10.1007/s10545-009-1081-4
Crushell E, et al. Negative Screening Tests in Classical Galactosaemia Caused By S135L Homozygosity. J Inherit Metab Dis. 2009;32(3):412-5. PubMed PMID: 19418241.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Negative screening tests in classical galactosaemia caused by S135L homozygosity. AU - Crushell,E, AU - Chukwu,J, AU - Mayne,P, AU - Blatny,J, AU - Treacy,E P, Y1 - 2009/05/08/ PY - 2008/10/23/received PY - 2009/03/19/accepted PY - 2009/03/15/revised PY - 2009/5/7/entrez PY - 2009/5/7/pubmed PY - 2009/8/20/medline SP - 412 EP - 5 JF - Journal of inherited metabolic disease JO - J Inherit Metab Dis VL - 32 IS - 3 N2 - 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. SN - 1573-2665 UR - https://www.unboundmedicine.com/medline/citation/19418241/Negative_screening_tests_in_classical_galactosaemia_caused_by_S135L_homozygosity_ L2 - https://doi.org/10.1007/s10545-009-1081-4 DB - PRIME DP - Unbound Medicine ER -