Glycolate oxidase deficiency in a patient with congenital hyperinsulinism and unexplained hyperoxaluria.

BACKGROUND: A baby girl was born at 39 weeks gestation to consanguineous Asian parents. From day 1 of life she had severe hypoglycaemia with an inappropriately elevated insulin concentration consistent with congenital hyperinsulinism (CHI), confirmed by the finding of a homozygous mutation in ABCC8 (encoding the sulfonylurea receptor 1).

CASE DIAGNOSIS/TREATMENT: Urine organic acid analysis showed an incidentally elevated excretion of glycolate. Whilst this was unlikely to contribute to the hypoglycaemia, hyperglycolic aciduria is a known feature of primary hyperoxaluria type 1 (PH1); therefore oxalate was also measured in urine and found to be elevated. Sequence analysis of the genes involved in PH1 and also the two other known forms of primary hyperoxaluria revealed no pathological variants. PH1 was definitively excluded by enzyme activity analysis on a liver biopsy, which confirmed normal glyoxylate aminotransferase (AGT) activity and positive AGT immunoreactivity. Glycolate oxidase (GO) deficiency was considered, and thus gene sequencing of HAO1, which encodes GO, was performed. A homozygous change (c.493G>T p.(Gly165Cys)) was found in exon 3 of HAO1, predicted to be deleterious to protein function. Further analysis of the liver biopsy demonstrated absent GO enzyme activity, confirming GO deficiency in this case.

CONCLUSIONS: The results lead to the conclusion that this baby has two unrelated autosomal recessive conditions, CHI and GO deficiency, and also hyperoxaluria of unknown aetiology. Deficiency of GO is a very rare disorder with only two previously published cases. It is considered to be an essentially benign inborn error of metabolism. The present case is unique in that GO deficiency is associated with persistent hyperoxaluria.