Krabbe disease is an autosomal recessive leukodystrophy where a deficiency of the galactosylceramide beta-hydrolase enzyme leads to accumulation of toxic substances which cause demyelination in both central and peripheral nervous systems. It is classified into early infantile, late infantile, juvenile and adult types based on the age of presentation. MRI of the brain in patients with Krabbe disease shows bilaterally symmetrical T2 hyperintense signal in the periventricular and deep white matter and in the corticospinal tracts. Patients can have peripheral neuropathy, which, on imaging, is commonly seen in the form of thickening and enhancement of cranial nerves and nerve roots of cauda equina. Our patient, a child aged eleven years, had intracranial lesions along with brachial plexopathy. This is the first described case of juvenile-onset Krabbe disease with brachial plexus involvement.

Krabbe disease (KD) can be classified into early-infantile, late-infantile, juvenile, and adult form subtypes. Adult form KD is relatively rare and lacks systematic characterization of clinical, imaging, and lipidomic features. This cross-sectional study aimed to define characteristic white matter hyperintensities and plasma lipidomic profiles to identify potential correlations with clinical severity. Eleven patients with adult-onset from eight pedigrees were enrolled. Galactocerebrosidase (GALC) variants were identified by whole-exome sequencing. Clinical, electrophysiological and MRI evidence were collected, with MRI severity quantified using a modified scoring system. Plasma lipidomic profiles were obtained by liquid chromatography-tandem mass spectrometry were analyzed for correlations with clinical severity scores and imaging features. All adult KD patients harbored GALC variants, including two novel variants (p. Gly512Cys, p. Asn280Valfs*12). The p. Leu634Ser variation was the most prevalent (six pedigrees) without founder effect. All patients manifested leukodystrophy and half exhibited extensive white matter hyperintensities. MRI severity score didn't correlate with Spastic Paraplegia Rating Scale (SPRS) or onset age. While psychosine (PSY) remained normal, ceramide and sphingosine elevations were observed. Ceramide negatively correlated with onset age (R = -0.815, P = 0.048) and positively with duration-adjusted SPRS (R = 0.979, P = 0.004). Extensive white matter hyperintensity is a characteristic radiological feature of adult-onset Krabbe disease. PSY levels cannot serve as biomarker of adult-onset KD. Elevated plasma ceramides and sphingosine warrant exploration as candidate biomarkers of disease severity.

The challenges faced by patients with Krabbe disease remain unelucidated. This study aimed to identify these challenges and facilitate the development of methods for assessing the quality of life. This qualitative descriptive study used in-person or online semistructured interviews from March to December 2022 using a qualitative content analysis approach. Data were collected from one patient each for the late infantile, juvenile, and adult types of Krabbe disease. In total, 249 codes were extracted from the verbatim transcripts and integrated into 40 subcategories and eight categories. The categories were integrated into three themes: the impact of symptoms on daily life, challenges for healthcare systems, and challenges faced by family members. Patients experienced physical symptoms, social life challenges, and medical care difficulties. Additionally, families felt burdened caring for these patients. In conclusion, support systems for patients and their families during treatment and in their living environments should be developed to aid in managing these challenges. Moreover, a comprehensive scale that accurately reflects the social challenges faced by these patients and their families is needed.

Krabbe disease (KD) is a rare autosomal recessive lipid storage leukodystrophy. It is caused by deficient enzyme activity resulting from mutations of the β-galactocerebrosidase (GALC) gene. KD is distinguished into subtypes based on the age of onset; these are early infantile, late infantile, juvenile, and adult-onset. We report a case of a 47-year-old Caucasian man with a 2-year history of muscle atrophy and weakness in both hands associated with pyramidal signs and mild spasticity in the lower limbs. An extensive work-up led this motor neuron disease-like disorder to be diagnosed as adult-onset KD. The patient was found to be compound heterozygous for two GALC mutations (p.G286D and p.Y490N). These two rare missense mutations have previously been reported with other heterozygous mutations. However, their co-occurrence in a KD patient is novel. From the perspective of this case, we review the current literature on compound heterozygous mutations in adult-onset KD and their phenotypic variability.

Krabbe disease is a progressive neurologic disorder caused by deficiency of the lysosomal enzyme galactocerebrosidase. The disease commonly has an early-infantile onset, but can have late-infantile, juvenile, or adult-onset phenotypes. Classic computed tomography (CT) and magnetic resonance imaging (MRI) findings in Krabbe have been well described. We report a patient, ultimately diagnosed with juvenile-onset Krabbe, who presented with atypical CT imaging and rapid disease progression. Our patient was a previously healthy and developmentally appropriate female who presented at 3 years 4 months of age with ataxia and motor regression that had progressed over the course of 6 weeks without an identifiable catalyst. CT, performed in the emergency setting, demonstrated extensive white matter hyperdensity. Subsequent MRI showed T2 hyperintensity of the white matter corresponding to the areas of hyperdensity on the CT, as well as enhancement of multiple cranial nerves bilaterally, suggestive of Krabbe disease. Enzymatic testing demonstrated low galactocerebrosidase activity and molecular testing of GALC revealed compound heterozygosity for 2 known pathogenic mutations, consistent with a diagnosis of Krabbe Disease. This included the common 30-kb deletion and a known pathogenic mutation associated with juvenile/adult-onset disease. Our patient's diffuse hyperdensity on CT offers a new radiographic finding to include in the repertoire of Krabbe imaging, and thus aide in the diagnostic evaluation. The rapidity of progression our patient demonstrated is additionally unique and should be considered in the identification of juvenile Krabbe as well as the complicated decision-making process regarding potential treatments.