Case of the Week
Section Editors: Matylda Machnowska1 and Anvita Pauranik2
1University of Toronto, Toronto, Ontario, Canada
2BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
Sign up to receive an email alert when a new Case of the Week is posted.
July 1, 2021
Infantile Krabbe Disease (Globoid Cell Leukodystrophy)
- Background:
- Krabbe disease is a rare autosomal recessive lysosomal storage disorder caused by deficiency in the galactocerebrosidase (GALC) enzyme.
- Deficiency of the GALC enzyme results in accumulation of psychosine during normal myelination, which is hypothesized to cause the pathologic changes of globoid cell formation and decreased myelin in the central and peripheral nervous systems.
- The GALC gene has been located to chromosome 14q31.
- Incidence is estimated between 1:100,000 and 1:400,000.
- Clinical Presentation:
- Most patients present in the first 12 months of life (infantile form).
- Infantile onset presents with irritability, developmental delay or regression, limb spasticity, axial hypotonia, absent reflexes, and optic atrophy (pale disc on fundoscopy).
- Key Diagnostic Features:
- Periventricular and deep white matter T2 high signal with a propensity for early involvement of the cerebellum and corticospinal tracts; subcortical U-fibers are spared until the late stage
- White matter signal abnormality may have a “tigroid” appearance (related to sparing of the perivascular white matter), although this is traditionally associated with metachromatic leukodystrophy (another lysosomal storage disorder).
- Hyperdensity on CT/low T2 signal on MRI in the thalami or basal ganglia
- Cranial nerve enhancement and hypertrophy of the optic nerve and chiasm
-
MRS shows elevated choline, myo-inositol, and creatine, with moderate NAA.
-
Definitive diagnosis is made on molecular genetic testing in individuals with abnormally low GALC activity in leukocytes isolated from whole blood or cultured skin fibroblasts.
-
Newborn screening has been implemented in some areas of the United States and for at-risk siblings.
- Differential Diagnoses:
- Metachromatic leukodystrophy: Progressive cerebral white matter T2 high signal with a posterior predominance and no early involvement of the cerebellum; spares subcortical U-fibers; T2 low signal in the thalami or basal ganglia (less so than in Krabbe disease)
-
Neuronal ceroid lipofuscinosis: Heterogeneous group of diseases with a range of clinical symptoms and age of presentation; T2 low signal in the thalami or basal ganglia; mild white matter and internal capsule T2 hyperintensities; cerebellar atrophy
-
Tay-Sachs disease (and other GM2 gangliosidoses): Patchy white matter T2 high signal; T2 low signal/CT hyperdensity in the thalami; cerebellar and spinal cord atrophy
-
Neurofibromatosis type 1: Optic nerve enlargement secondary to optic nerve glioma; focal areas of T2/FLAIR high signal (FASI)
-
Treatment:
-
If untreated, the infantile form is fatal by 1 to 2 years of age.
-
Hematopoietic stem cell transplant has been shown to improve survival and severity of neurologic symptoms in infants who are asymptomatic or minimally symptomatic.
-
Survival is not improved in symptomatic infants following transplant.
-
Current Issue
Case Collections
