Abstract Details

Title Not-so-adult Onset Krabbe Disease in a Toddler

Topic Child Neurology and Developmental Neurology

Presentation(s) P7 - Poster Session 7 (8:00 AM-9:00 AM)

Poster/Presentation
Number 8-005

Objective To highlight an atypical MRI pattern and haplotype effects in an 18-month-old patient with late infantile-onset Krabbe Disease (LIKD).

Background Krabbe disease occurs due to deficiency of the enzyme galactocerebrosidase (GALC), leading to toxic accumulation of psychosine and progressive demyelination. Phenotypic spectrum, including age of onset and severity, is determined by GALC genotype, residual GALC activity, and psychosine levels. LIKD presents between 6 and 36 months and typically predominantly involves the periventricular white matter (PVWM) and deep gray nuclei.

Design/Methods Case report and literature review. ChatGPT 5.0 was used during literature review.

Results Case Report: This child, previously typically developing, presented with 2 months of severe motor developmental regression and lower limb stiffness. Examination showed intact mentation with bulbar weakness, axial hypotonia, and spastic hypertonicity and extensor posturing of the legs. MRI demonstrated symmetric T2-FLAIR hyperintensities of the corona radiata and posterior PVWM extending along the corticospinal tracts (CST) without involvement of the deep grey nuclei or infratentorial white matter. Ultrarapid whole genome sequencing yielded 5 heterozygous variants in GALC, two likely pathogenic (c.850 G>A, p.G284S and c.939_941del, p.Y314del), one of uncertain significance (c.1760 T>C, p.I587T), and two possibly benign modifiers/pseudodeficiency variants. Together with clinical presentation and elevated psychosine levels, this was diagnostic for LIKD.

Conclusions

CST-predominant demyelination without significant involvement of additional sites, an imaging phenotype associated with juvenile/adult-onset Krabbe, has only been reported in rare cases of LIKD and likely explains the patient’s motor predominance and relative cognitive-sparing presentation. The combination of the heterozygous G284S and I587T variants is associated with quickly progressive LIKD, illustrating haplotype effects. We suspect one or more of the other variants are acting as modifiers, potentially contributing to this unique imaging and clinical phenotype. Our case highlights the importance of recognizing the full spectrum of neuroimaging findings for timely diagnosis of genetic and metabolic disorders.

Authors/Disclosures
Xinran Xiang, MD (Oregon Health & Science University) PRESENTER	Dr. Xiang has received personal compensation in the range of $0-$499 for serving as a Author with The New Yorker/Conde Nast.
Aditi Tiwari, MBBS, MD Pediatrics	Dr. Tiwari has nothing to disclose.
Seva Khambadkone	Dr. Khambadkone has nothing to disclose.
Michael Regner, MD	Dr. Regner has nothing to disclose.
Anna Dennis, MS, CGC	Ms. Dennis has nothing to disclose.
Amy C. Yang, MD	The institution of Dr. Yang has received research support from Sequitur Health Corp.
Kimberly A. Kripps, MD	Dr. Kripps has nothing to disclose.

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