Neuroradiological, neurophysiological and molecular findings in infantile Krabbe disease: two case reports

Abstract

Krabbe disease is an autosomal recessive neurodegenerative disorder due to a defect of the lysosomal enzyme β-galactocerebrosidase (β-GALC). Depending on the age of onset, the disease is classified into infantile and later-onset forms. We report neuroradiological, neurophysiological and molecular findings in two Greek patients with the infantile form of Krabbe disease. The index patients presented at the age of 3.5 and 6 months, respectively, due to developmental delay. Magnetic resonance imaging (MRI) of the first patient’s brain demonstrated signs of leukodystrophy, while nerve conduction velocities (NCVs) were significantly decreased. The second patient’s MRI at the age of 4 months was initially normal, but at 18 months demonstrated leukodystrophic alterations as well, whereas NCVs were also significantly delayed. In both patients, a severe decrease in β-GALC, activity supported the diagnosis of Krabbe disease, while the final diagnosis was confirmed by molecular genetic testing. Two homozygous mutations of the GALC gene, the c.411_413delTAA [p.K139del] mutation in the first patient, and the c.749T>C [p.I250T] mutation in the second patient, were identified. At their last follow-up visit at the age of 4 and 6 years, respectively, both patients were bedridden and quadri-plegic, suffering from frequent respiratory tract infections and fed through a gastrostomy. Both mutations found in homozygosity in these two unrelated patients of Greek ancestry, could pinpoint a common origin. Genotyping of patients with Krabbe disease is important, in order to contribute to the creation of a European mutation database and to further study possible genotype-phenotype correlations of the disease.

Clinical and molecular findings in 6 Turkish cases with Krabbe disease

“…11 Homozygosity of this mutation has been reported in cases with three early-onset findings, two of which were Greek and the remaining one was Turkish. [11][12][13] In addition to the previous reports of compound heterozygous cases with late-onset KD, the homozygosity leading to infantile-onset disease in our cases demonstrates that the homozygosity of this mutation leads to more severe disease. This mutation can be seen in Turkish cases as well as in the Greek population.…”

Elektroneurografische und elektromyografische Diagnostik in der Neuropädiatrie

“…Monat) respektiven spät ( nach dem 8 Monat) manifest werdenden Krabbe Patienten. Bei den früh auftretenden Fällen waren die NLG in 100 % verlangsamt, während die spät manifest werdenden Patienten nur in 20 % verlangsamte NLGʼs zeigten [13].…”

From pathological mechanisms in Krabbe disease to cutting‐edge therapy: A comprehensive review

“…‐Second stage: intensification of symptoms observed in first phase (hypertonicity and opisthotonus, psychomotor and growth regression, peripheral neuropathy, apnea episodes, frequent epileptic seizures † , 82–86 hand‐grip difficulties, and visual impairments ‡ )…”