Inborn errors presenting with neurological regression — branching viva

Opening branch — the regressing toddler

A two-year-old who was speaking in two-word phrases and running has stopped speaking and begun to stumble over four months. The candidate must first confirm that this is true regression - loss of previously acquired skills - distinguished from delay, plateau, and a static deficit by a meticulous developmental history anchored to earlier milestones. The candidate states that regression mandates a search for a progressive and potentially treatable cause at speed, because the commonest error is reading a static deficit as progressive or, conversely, labelling a treatable IEM as cerebral palsy. ^[3]

The examiner probes the classification. The candidate groups the regressing IEM by affected pathway - intoxicating small-molecule, energy or mitochondrial, storage or lysosomal, and lipid-traffic and metal - and explains that the pathway predicts the bedside pattern, the first-line test, and whether a disease-modifying therapy exists. The teaching point is that a treatable subset spans every group, which is why the governing principle is to exclude the treatable IEM before labelling a child degenerative. ^{[1] [3]}