Akademik Veri Yönetim Sistemi
International Congress of Inborn Errors of Metabolism 2025, Kyoto, Japonya, 2 - 06 Eylül 2025, (Yayınlanmadı)
Introduction
Krabbe disease(KD; OMIM #245200) is a
lysosomal storage disorder caused by deficiency of galactocerebrosidase(GALC; EC 3.2.1.46)
encoded by GALC gene. Based on the age of onset, KD is divided into early-onset
and late-onset forms. The early-infantile form accounts for about 80% of cases.
It is characterised by severe neurological symptoms including
hyperirritability, feeding difficulties, axial hypotonia, lower limb
spasticity, peripheral neuropathy and clonus. The adult-onset form progresses
more slowly with predominant features of
sensorimotor polyneuropathy and spastic paraplegia. The aim of this
study was to evaluate the clinical and molecular features of patients diagnosed
with KD.
Material and Methods
This cross-sectional descriptive study was
conducted in four metabolic centres in Turkey, with data collected between
2020-2024. Patient demographics, physical examination and laboratory results,
and GALC gene molecular analyses were retrospectively reviewed.
Results
Of the ten patients included, five were male
and eight had a history parental consanguinity. Among the five early infantile
KD cases, the median age of symptom onset was 5 months (range: 3.5-12 months)
and the median age at diagnosis was 9 months (range: 5-36 months). Two siblings
presented with regression of acquired skills, and the remaining patients
presented with loss of head control, seizures and feeding difficulties. Three
patients died from disease-related complications -two from aspiration and sepsis
at 39 and 44 months, and one from sudden infant death at 9 months. The two
surviving patients had significant developmental delays and required nasogastric feeding. One
underwent a ventriculoperitoneal shunting for
hydrocephalus.
The late-onset KD group included two siblings
diagnosed at 8 and 12 years of age, both of whom had early seizures(at 18 and
24 months) followed by developmental regression. Electromyography revealed
myopathy, and follow-up examinations revealed developmental delay, dystonia,
dysmetria, dysdiadochokinesia and gait disturbance. One male patient was
diagnosed at the age of 52 years after presenting with muscle weakness at the
age of 35 years. Electromyography showed progressive polyneuropathy and cranial
MRI showed white matter hyperintensities and cortical atrophy on T2-weighted
images. Family screening identified GALC gene variants in two out of
four offspring.
CONCLUSION
In this study, all patients with late-onset
KD were diagnosed using whole exome sequencing (WES) highlighting the utility
of WES in identifying atypical
presentations of KD. This study documents
the clinical course of early infantile KD and highlights the importance of
considering inherited metabolic disorders, in adult patients with unexplained
neurological symptoms.