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We report on a 5‐year‐old female born to consanguineous parents, ascertained at the age of 23 months for an elevated plasma methionine level, a mildly abnormal total plasma homocysteine (tHcy), and elevated aminotransferases. She had global developmental delay, microcephaly, dysmorphic facial features, hypotonia, nystagmus and tremor in her upper extremities. Metabolic investigations demonstrated elevations in plasma methionine, plasma S‐adenosylmethionine (SAM) and plasma S‐adenosylhomocysteine (SAH), with normal urine adenosine levels. Some of the elevations persisted for over 1 year. Sequencing of the ADK and AHCY genes was negative for causative variants. Plasma methionine normalized 1 year after ascertainment, but SAM and SAH continued to be elevated for six more months before normalization, and aminotransferases remained mildly elevated. Whole exome sequencing demonstrated a homozygous pathogenic variant; {"type":"entrez-nucleotide","attrs":{"text":"NM_018297.3","term_id":"223941793","term_text":"NM_018297.3"}}NM_018297.3(NGLY1):c.1405C>T (p.Arg469*) in exon 9 of the NGLY1 gene, for which both parents were heterozygous. To our knowledge, this is the first report of NGLY1 deficiency with elevations in plasma methionine, SAM and SAH and a slight elevation of tHcy. Less than 20 patients have been reported with NGLY1 deficiency worldwide and this case expands on the biochemical phenotype of this newly discovered inborn error of metabolism.

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.