Krabbe disease

Krabbe disease AKA globoid cell leukodystrophy

Infantile (3m-6m), juvenile, adult form

Infantile: 

1. Symptoms/clinical progression

   1. Restlessness

   2. Hyperactive

   3. Intermittent fever

   4. Feeding problems

   5. Delayed development. 

   6. optic atrophy and hyperacusis often develop. 

   7. Apnea, 

   8. need for nasogastric feeding. 

   9. In the end flaccid and bulbar signs

   10. Death within first years of life

2. Typical image

• 1. T1 bright thalami

  2. T1 PLIC not bright

  3. T2 cerebellar nuclei remain hyperintense in center

  4. T2 corticospinal tracts hyperintense in internal capsule, medial medullary pyramids

  5. T2 sometimes stripes in white matter with perivenular clusters of globoid cells

3. Progression

• 1. CT:Hyperdense and T1 hyperintense thalami, caudate, corona radiata, dentate nuclei. 

  2. - >T2 bright posterior frontal and anterior parietal

  3.  - > T2 hyper and T1 hypo: central cerebral (early on sparing of subcortical white matter) and cerebellar white matter and cerebellar nuclei 

  4. -> diffuse white matter atrophy.

4. Enhancement

• 1. has been reported in cauda equina and cranial nerves

5. Acute DWI

• 1. (-) ADC subcortical white matter, caudate head, anterior limb of internal capsule

6. Chronic DWI

• 1. (+) General increased in White matter

7. MRS

• 1. infantile:mainly in white matter: (++) choline, (++) myo-Inositol, (-)NAA, sometimes (+) lactate

  2. juvenile: (+) myo-Inositol in white matter

  3. adult: in white matter(-)NAA, (+)creatine,(+)choline,(+) myo inositol

8. Protein:

• 1. Galactosylseramide beta-galactosidase deficiency

  2. Key component in myelin turnover and breakdown

9. Accumulation:

• 1. Galatosylsphingosine, toxic to neurons oligodendrocytes and schwann cells.

10. Pathology:White matter replaced with rubbery translucent material. Pseudocysts at frontal horns and corpus callosum. Severe neuron loss most pronounced in CC, corona radiata,  cerebellar peduncles

11. Source

• 1. Barcovich

12. Organelle

• 1. Lysosomal enzyme

13. OMIM

• 1. 245200

14. Gene/chromosome

• 1. GALC 14q31