Fact-sheet: Krabbe disease


Updated on 09/17/2021 at 12:16 PM

Note : 0/10
Share

View all RADEOS cases associated with this fact-sheet

Definition

Autosomal recessive lysosomal deficiency of galactocerebrosidase enzyme (galactosylceramidase 1).
Mutation located on Chromosome 14.
Secondary leukodystrophy due to accumulation of cerebroside and psychosine.
Prevalence 1/100,000 in Europe.
Synonyms: GALC deficiency, Globoid cell leukodystrophy

Clinical features

Neonatal form: 2 months to 3 years
-Stage 1: irritability, stiffness, feeding difficulties, hyperthermia episodes, growth delay.
-Stage 2: hypertonic episodes, opisthotonos
-Stage 3: hypotonia, blindness, deafness
Infantile and adult forms: blindness, cerebellar ataxia, spasticity, polyneuropathy, dementia, psychosis

Laboratory findings

-enzymatic assays on leukocytes or cultured fibroblasts, revealing GALC deficiency in nearly all cases.
-histology: characteristic multinucleated globoid cells of macrophage origin, containing undigested galactocerebroside, present in the white matter.
-Genetics: mutation analysis confirms the diagnosis. (65 different mutations described)

CT

-Spontaneous hyperdensity of the thalami, basal ganglia, corona radiata, and dentate nuclei.
-Hypodensity of the deep periventricular white matter

MRI

-SE T1: spontaneous T1 hyperintensity of the thalami
-FSE T2: T2 hyperintensity of the deep periventricular white matter, dentate nuclei, and corticospinal tracts.
-Diffusion: restricted diffusion with possible ADC decrease related to axonal swelling.
-SE T1 C+: possible enhancement of the cranial nerves as well as of the normal-abnormal white matter junction.
-Spectroscopy: reduced NAA. Choline peak. +/- lactate. Nonspecific.
-Enlargement of the optic nerves related to accumulation of globoid cells.
-Cortical-subcortical atrophy over the course of disease

Differential diagnosis

-Adrenoleukodystrophy: progressive demyelination from the splenium of the corpus callosum to the deep periventricular parietal white matter, typical.
-Metachromatic leukodystrophy: demyelination of the periventricular white matter. In the 2nd year of life.
-Maple syrup urine disease: cerebellar and perirolandic white matter edema.
In the first days of life.