Krabbe disease, also known as globoid cell leukodystrophy, is an autosomal recessive leukodystrophy.
Can vary and depends on age of onset 5.
- delayed milestones
- loss of developed milestones
There are at least two recognised forms 3,5:
- infantile form (85-90%): rapidly progressive usual onset <2 years of age
- late onset / adult form (10-15%): more slowly progressive
The formation of globoid cells (hence the name) is characteristic of the disease. It is caused by a deficiency of galactocerebroside ß-galactosidase, an enzyme that degrades cerebroside, a normal constituent of myelin. Cerebrosides accumulate in the lysosomes of macrophages within the white matter. This results in demyelination.
There is deficiency of the lysosomal enzyme galactocerebrosidase (GALC) which is a component in myelin metabolic turnover. This has been mapped to chromosome 14q.
Changes typically involve the corticospinal tracts.
May show hyperdense areas symmetrically involving the thalami 1 (case 1) , cerebellum, caudate nuclei, posterior limbs of the internal capsule, and brainstem. Changes may also extend into the centrum semiovale/corona radiata region 4-5.
- T2: may show high signal involving periventricular white matter 2 centrum semiovale and deep gray matter; subcortical U-fiber may be spared until late in the course of the disease 5
- T1 C+ (Gd): no contrast enhancement in these areas 2
- MRS: adult form may show abnormal choline elevation in centrum semiovale 7
Treatment and prognosis
Often tends to be progressive and fatal 5.
History and etymology
It is named after Knud Haraldsen Krabbe, a Danish neurologist (1885-1961) 6.
If similar imaging appearances are seen in an adult, consider amyotrophic lateral sclerosis (ALS) when there is corticospinal tract involvement.
Inborn errors of metabolism
- disorders of carbohydrate metabolism
- disorders of amino acid metabolism
disorders of the urea cycle
- carbamoyl phosphate synthetase I deficiency
- ornithine transcarbamylase deficiency (OTCD)
- disorders of organic acid metabolism
- disorders of fatty acid oxidation and mitochondrial metabolism
- disorders of porphyrin metabolism
- disorders of purine or pyrimidine metabolism
- disorders of steroid metabolism
- disorders of mitochondrial function
- disorders of peroxisomal function
lysosomal storage disorders
- activator Deficiency/GM2 Gangliosidosis
- cholesteryl ester storage disease
- chronic hexosaminidase A Deficiency
- Danon disease
- Fabry disease
- Farber disease
- Gaucher disease
- GM1 gangliosidosis
- I-Cell disease/Mucolipidosis II
- infantile free sialic acid storage disease
- juvenile hexosaminidase A deficiency
- Krabbe disease
- lysosomal acid lipase deficiency
- metachromatic Leukodystrophy
- multiple sulfatase deficiency
- Niemann-Pick disease
- meuronal ceroid lipofuscinoses
- CLN6 disease
- Finnish Variant Late Infantile CLN5
- Jansky-Bielschowsky disease
- Kufs disease
- northern epilepsy
- Santavuori-Haltia disease
- Pompe disease
- Sandhoff disease
- Schindler disease
- Salla disease
- Tay-Sachs disease
- Wolman disease
- 1. Farina L, Bizzi A, Finocchiaro G et-al. MR imaging and proton MR spectroscopy in adult Krabbe disease. AJNR Am J Neuroradiol. 2000;21 (8): 1478-82. AJNR Am J Neuroradiol (full text) - Pubmed citation
- 2. Given CA, Santos CC, Durden DD. Intracranial and spinal MR imaging findings associated with Krabbe's disease: case report. AJNR Am J Neuroradiol. 2001;22 (9): 1782-5. AJNR Am J Neuroradiol (full text) - Pubmed citation
- 3. Provenzale JM, Peddi S, Kurtzberg J et-al. Correlation of neurodevelopmental features and MRI findings in infantile Krabbe's disease. AJR Am J Roentgenol. 2009;192 (1): 59-65. doi:10.2214/AJR.07.3885 - Pubmed citation
- 4. Choi S, Enzmann DR. Infantile Krabbe disease: complementary CT and MR findings. AJNR Am J Neuroradiol. 14 (5): 1164-6. AJNR Am J Neuroradiol (abstract) - Pubmed citation
- 5. Cheon JE, Kim IO, Hwang YS et-al. Leukodystrophy in children: a pictorial review of MR imaging features. Radiographics. 22 (3): 461-76. Radiographics (full text) - Pubmed citation
- 6. Schlesch T, Fog T. Bibliography of the works of Knud H. Krabbe. Acta Psychiatr Neurol Scand. 1955;30 (1-2): VII-XIX. - Pubmed citation
- 7. Farina L, Bizzi A, Finocchiaro G et-al. MR imaging and proton MR spectroscopy in adult Krabbe disease. AJNR Am J Neuroradiol. 2000;21 (8): 1478-82. AJNR Am J Neuroradiol (full text) - Pubmed citation
- 8. Wenger DA. Krabbe Disease. 2000 Jun 19 [Updated 2011 Mar 31]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1238/