# Very late-onset Krabbe disease with concomitant dementia: case description and a critical review of the literature

## TL;DR

This paper describes a rare case of Krabbe disease in an elderly patient and reviews adult-onset cases to better understand the condition's late manifestations.

## Contribution

The study provides a comprehensive review of late-onset Krabbe disease and highlights its under-recognized presentation in older adults.

## Key findings

- Spastic paraplegia is the most common manifestation in later-onset Krabbe disease.
- Most adult-onset cases involve cortico-spinal tract abnormalities visible on brain MRI.
- Five adult-onset patients were asymptomatic despite pathogenic GALC variants.

## Abstract

Krabbe disease (KD) is a rare autosomal recessive lysosomal storage disorder caused by pathogenic variants in GALC. Despite accounting only for 5% of forms, reports of adult-onset KD cases are increasingly described.

A female patient manifesting KD after the age of 60 years, presenting with spastic paraplegia and cognitive decline, is described. The scientific literature of KD with onset > 10 years has been extensively reviewed to refine the spectrum of later-onset KD manifestations.

Including ours, we identified 84 KD adolescent/adult-onset patients (mean age at onset 28.7 ± 14.2 years). Most patients had limb spasticity as main characterizing neurological feature (58/84, 70.2%), followed by polyneuropathy (11/ 84, 13.1%), both upper and lower motor neuron signs (2/84, 2.4%), and epilepsy (2/84, 2.4%). Five out of 84 patients (6.0%) were asymptomatic. Most patients had cortico-spinal tracts involvement at brain MRI. The most common pathogenic GALC variants were the c.1901 T > C (18 patients), the c.857G > A (13 patients), and the c.1161 + 6532_polyA + 9kbdel (13 patients).

Complicated spastic paraplegia is the most common manifestation in later-onset KD, rarely with normal brain MRI. KD should be always considered also in cases with very late-onset spastic paraplegia.

The online version contains supplementary material available at 10.1007/s10072-026-08836-5.