Globoid Cell Leukodystrophy (Krabbe Disease)

Gabriella, Sinkó and Eszter, Dénes and Gábor, Farkas and Tompa, Márton and Kálmán, Bernadette (2026) Globoid Cell Leukodystrophy (Krabbe Disease). IDEGGYOGYASZATI SZEMLE / CLINICAL NEUROSCIENCE, 79 (7-8). pp. 284-288. ISSN 0019-1442

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Abstract

Background – Globoid cell leukodystrophy or Krabbe disease is a rare condition caused by biallelic pathogenic variants in the GALC gene. Accumulation of the metabolic intermedier galactosyl ceramide and psychosine leads to the death of myelin-producing cells. Demyelination results in large amounts of myelin debries that exceed the clearence capacity of microglial cells and macrophages and cause their transformation into globoid cells. Case presentation – We present the case of a currently 17 months old girl whose motor and cognitive development was noted to be delayed at 4 month of age. She had episodes of febrile enteritis followed by focal seizures and spasms with increasing frequency. Her neurological exam was significant for irritability, lack of eye contact, lethargy, increased limb tone, axial hypotonia, few spontaneous movements, sluggish deep reflexes, frequent myoclonus, and automatisms (chewing motions). The seizures were difficult to control. Her cranial MRI revealed confluent white matter abnormalities in the hemispheral white matter, cerebellum and brainstem suggesting an underlying metabolic abnormality. Whole exome sequencing identified two likely pathogenic variants in trans within the GALC gene, establishing the diagnosis of globoid cell leukodystrophy. At the time of diagnosis, hematopoietic stem cell transplantation (HSCT) was not recommended due to the advanced disease. Antiseizure medications and supportive therapy have been the means of controlling her symptoms. Conclusion – Infantile Krabbe disease is a se vere progressive disorder leading to death in 2-3 years. The only currently approved disease modifying therapy is HSCT that is effective only in early stages and is not without risks itself. There are numerous preclinical and clinical studies involving various forms of corrective gene therapy that may halt or reverse the course of this dismal condition. Keywords: Krabbe disease, globoid cell leukodystrophy, GALC gene, whole exome sequencing

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