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Synonyms: globoid cell leukodystrophy, globoid cell leukoencephalopathy, galactosylceramide lipidosis, galactosylceramidase (GALC) deficiency
This is an autosomal recessive leukodystrophy. There is a lack of the enzyme galatosylceramidase (GALC) leading to abnormalities of myelin formation in both the central and peripheral nervous system. It is often fatal.
The mutation in Krabbe's disease is located to the human chromosome 14 and more than 40 mutations have been identified. This mutation of the galactosylceramidase (GALC) gene leads to a GALC deficiency. Deficiency of this enzyme leads to an inability to break down lipids in the myelin, leading to reduced myelin production. However, it has been observed that this genotype alone may not account for the phenotype, suggesting that other genetic factors may also be important.[2, 3]
There are two types of presentation:
- Infantile form - the most common, with affected infants being normal at birth. 80% of cases develop features and are diagnosed in the first six months of life.
- Late-onset form - later presentation including adulthood; rarer and milder, with slower progression.
These usually occur at 3-6 months:
- Feeding difficulties.
- Limb stiffness.
- Delayed achievement of developmental milestones.
- Cherry red spots.
- Protruding ears.
- Postural tremor of limbs.
- Pyramidal paresis of limb or limbs.
- Extensor plantar responses.
- Unsteadiness of gait.
- Psychomotor retardation.
Adults commonly present with motor skill problems, paraesthesia, weakness and cognitive deficits.
- Galactosylceramidase (GALC) enzyme activity - from blood or skin fibroblasts (activity reduced).
- MRI - demyelination of white matter of the brain and, more rarely, the spinal cord.[5, 6]
- Lumbar puncture will show raised CSF protein.
- Nerve conduction - can be normal; however, most have some abnormalities, eg delayed brainstem auditory evoked potentials and visual evoked potentials.
- Histology - presence of PAS-positive material extracellularly and cerithin in microglial cells with characteristic 'globoid cells' in brain tissue.
- Genetic studies.
This can be performed with chorionic villous sampling.
- There is no cure yet and thus management is mainly supportive, eg physiotherapy, anticonvulsants.
- Allogeneic haematopoietic stem cell transplantation in early disease leads to reversal of CNS deterioration.[7, 8]
- Transplantation of umbilical cord blood from unrelated donors leads to neurological improvement in those who received this therapy before the development of symptoms.
Parents and carers will need education and support. Parents will require genetic counselling before further pregnancies.
Poor in infantile forms with death usually before the age of 2 years. However, some cases have been reported to live beyond the teens. In late-onset disease, cases progress slower and the spectrum and severity of the illness are very variable.
Further reading and references
; Stem cell-based strategies for treating pediatric disorders of myelin. Hum Mol Genet. 2008 Apr 1517(R1):R76-83.
; Six novel mutations detected in the GALC gene in 17 Japanese patients with Krabbe disease, and new genotype-phenotype correlation. J Hum Genet. 200651(6):548-54. Epub 2006 Apr 11.
; Intracranial and spinal MR imaging findings associated with Krabbe's disease: case report. AJNR Am J Neuroradiol. 2001 Oct22(9):1782-5.
; Correlation of neurodevelopmental features and MRI findings in infantile Krabbe's AJR Am J Roentgenol. 2009 Jan192(1):59-65.
; Peripheral neuropathy in Krabbe disease: effect of hematopoietic stem cell transplantation. Neurology. 2006 Jul 2567(2):268-72.
; Krabbe disease treated with hematopoietic stem cell transplantation: serial assessment of anisotropy measurements--initial experience. Radiology. 2005 Jul236(1):221-30.
; Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease. N Engl J Med. 2005 May 19352(20):2069-81.
Hi all, I am a newbie here. I am 37 and 11 weeks pregnant with my second baby. I was 28 at the time of first delivery and haven't done any genetic testing at that time. But I know the risk factors...Zaynah
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