JIMD Reports, Volume 39

Paula J. Waters, Thomas M. Kitzler, Annette Feigenbaum, Michael T. Geraghty, Osama Al-Dirbashi, Patrick Bherer, Christiane Auray-Blais, Serge Gravel, Nathan McIntosh, Komudi Siriwardena, Yannis Trakadis, Catherine Brunel-Guitton, Walla Al-Hertani, Waters PJ, Kitzler TM, Feigenbaum A, Geraghty MT, Al-Dirbashi O, Bherer P, Auray-Blais C, Gravel S, McIntosh N, Siriwardena K, Trakadis Y, Brunel-Guitton C, Al-Hertani W, Waters, Paula J., Kitzler, Thomas M., Feigenbaum, Annette, Geraghty, Michael T., Al-Dirbashi, Osama, Bherer, Patrick, Auray-Blais, Christiane, Gravel, Serge, McIntosh, Nathan, Siriwardena, Komudi, Trakadis, Yannis, Brunel-Guitton, Catherine, Al-Hertani, Walla

Glutaric aciduria type 3 (GA3) is associated with decreased conversion of free glutaric acid to glutaryl-coA, reflecting deficiency of succinate-hydroxymethylglutarate coA-transferase, caused by variants in the SUGCT (C7orf10) gene. GA3 remains less well known, characterised and understood than glutaric aciduria types 1 and 2. It is generally considered a likely "non-disease," but this is based on limited supporting information, with only nine individuals with GA3 described in the literature. Clinicians encountering a patient with GA3 therefore still face a dilemma of whether or not this should be dismissed as irrelevant.We have identified three unrelated Canadian patients with GA3. Two came to clinical attention because of symptoms, while the third was identified by a population urine-based newborn screening programme and has so far remained asymptomatic. We describe the clinical histories, biochemical characterisation and genotypes of these individuals. Examination of allele frequencies underlines the fact that GA3 is underdiagnosed. While one probable factor is that some GA3 patients remain asymptomatic, we highlight other plausible reasons whereby this diagnosis might be overlooked.Gastrointestinal disturbances were previously reported in some GA3 patients. In one of our patients, severe episodes of cyclic vomiting were the major problem. A trial of antibiotic treatment, to minimise bacterial GA production, was followed by significant clinical improvement.At present, there is insufficient evidence to define any specific clinical phenotype as attributable to GA3. However, we consider that it would be premature to assume that this condition is completely benign in all individuals at all times.