Clin Chim Acta. 2023 Nov 01. pii: S0009-8981(23)00422-9. [Epub ahead of print]551 117620
Antoine Civit,
Paul Gueguen,
Helene Blasco,
Isabelle Benz-de-Bretagne,
Élodie Lebredonchel,
Giulia Dingeo,
Médéric Jeanne,
Sophie Rouxel,
Marine Tardieu,
Alexandre Raynor,
François Labarthe,
Arnaud Bruneel,
Violette Goetz.
Herein, we described the case of a newborn male, from consanguineous parents, who developed, at day 11 of life, an obstructive hydrocephalus resulting from bilateral cerebellar hemorrhage without evident cause. Then, at 1 month, he developed a fulminant hepatitis with hyperammonia, hyperlactatemia and metabolic acidosis. Infectious and first line metabolic explorations were normal. Screening for congenital disorder of glycosylation (CDG) was performed using capillary electrophoresis and western blot of serum transferrin. Abnormal results were evocative of mannose-phosphate isomerase deficiency (MPI-CDG or CDG-Ib) as it can be responsible for fulminant hepatitis, digestive disease, developmental delay, and coagulopathy. However, trio whole exome sequencing revealed a pathogenic variant at the homozygous state in ALDOB, responsible for hereditary fructose intolerance (HFI), an inherited metabolic disorder with excellent prognosis under a fructose-free diet. HFI had not been previously evoked in view of the absence of diet diversification, but meticulous inquiry revealed that parents systematically added white sugar to the bottle milk of their child, unintentionally triggering potentially fatal HFI decompensations. Early genetic analysis upsetted both diagnosis and prognosis for this infant who had excellent development after fructose removal. This full-of-surprises diagnostic approach illustrates the importance of an integrative collaboration between clinicians, biochemists, and geneticists.
Keywords: CDG; Congenital disorder of glycosylation; Fructosemia; Fulminant hepatitis; Hereditary fructose intolerance, fructosemia