Sweet ending: When genetics prevent a dramatic CDG diagnostic mistake.

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Newborns with unexplained severe symptoms pose diagnostic challenges.
• Congenital disorders of glycosylation (CDG) are often considered in such cases.
• Hereditary fructose intolerance (HFI) is a rare inherited metabolic disorder.

Observation:

• A male infant presented with obstructive hydrocephalus and later developed fulminant hepatitis, hyperammonia, and metabolic acidosis.
• Initial investigations for infections and common metabolic disorders were negative.
• Congenital disorder of glycosylation (CDG) screening suggested mannose-phosphate isomerase deficiency (MPI-CDG).

Findings:

• Trio whole exome sequencing identified a homozygous pathogenic variant in ALDOB, confirming hereditary fructose intolerance (HFI).
• The infant's symptoms were triggered by the unintentional introduction of sucrose into his diet.
• Diagnosis was complicated by the absence of typical dietary diversification in the infant's first month.

Implications:

• This case highlights the importance of considering HFI in neonates with severe metabolic decompensation, even without typical dietary triggers.
• Early genetic diagnosis and dietary management (fructose avoidance) led to an excellent clinical outcome.
• Integrated clinical, biochemical, and genetic approaches are vital for diagnosing complex pediatric metabolic disorders.