Phenotypic Variability of Krabbe Disease Across the Lifespan

Liao, Pamela; Gelinas, Jennifer N.; Sirrs, Sandra

doi:10.1017/s0317167100016188

Cited by 24 publications

(25 citation statements)

References 57 publications

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“…In addition, we did not measure brain atrophy, which is a known phenomenon in patients with Krabbe disease and those treated with transplantation. 6 The exclusion of brain atrophy from our data can possibly complicate our findings especially in regard to ventricular size as hydrocephalus ex vacuo is also seen in patients with brain atrophy. However, hydrocephalus ex vacuo is not associated with increased pressure; therefore, STV would not be expected in patients with hydrocephalus ex vacuo.…”

Section: Patients Without Stv Patients With Stvmentioning

confidence: 81%

“…1,2 Although most patients present before the age of 12 months (early infantile onset), later-onset forms with more variable presentation, late infantile (12 months to three years), juvenile (three to eight years), and adult (eight years and older), have been well characterized. [3][4][5][6] Common presenting symptoms in early infantile Krabbe disease include regression of developmental milestones, irritability, developmental delays, feeding difficulties, and abnormal muscle tone. 3 The median survival rates in early infantile disease range from two to three years of age.…”

Section: Introductionmentioning

confidence: 99%

“…3 The median survival rates in early infantile disease range from two to three years of age. 6,7 However, for patients who present early with minimal symptoms, medical interventions such as hematopoietic stem cell transplantation have shown to prolong median survival age while allowing some patients to live relatively normal lives into their teenage years. 8 Initial evaluation of a patient with Krabbe disease is based on a comprehensive history and physical examination.…”

Section: Introductionmentioning

confidence: 99%

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Spontaneous Third Ventriculostomy in Krabbe Disease

Zuccoli

Kim

Poe

et al. 2020

Pediatric Neurology

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a b s t r a c tIntroduction: Spontaneous third ventriculostomies have been reported in relation to obstructive hydrocephalus and increased intracranial pressure and are most commonly seen as disruption of the floor of the third ventricle. Hydrocephalus has been reported in patients with Krabbe disease; however, it is clinically difficult to monitor for hydrocephalus in patients with Krabbe disease as symptoms of increased intracranial pressure may overlap with symptoms of Krabbe disease. We describe a case series of spontaneous third ventriculostomy and hydrocephalus, likely in response to increased intracranial pressure, in patients with infantile Krabbe disease. Methods: Brain magnetic resonance images of patients with infantile Krabbe disease were retrospectively analyzed to assess for ventricular size and presence of spontaneous third ventriculostomies. A brain atlas was used to standardize the calculation of ventricular size. Mid-sagittal, T2-weighted images around the third ventricle were assessed for spontaneous third ventriculostomies. Developmental outcomes were measured with a series of standardized and validated tests. Results: Seventy-five patients with infantile Krabbe disease were evaluated. Twelve cases of spontaneous third ventriculostomies were identified. Head circumference (SE ¼ 8.07; P < 0.001) and average ventricular volume were greater (left: SE ¼ 1.47, P < 0.001) in patients with spontaneous third ventriculostomies when compared with patients without spontaneous third ventriculostomies. Patients with spontaneous third ventriculostomies also had more delayed development in adaptive (difference ¼ 0.2, P < 0.01), gross motor (difference ¼ 0.0, P < 0.01), and fine motor (difference ¼ 0.1, P < 0.001) function. Conclusions: Spontaneous third ventriculostomies, likely in the context of increased intracranial pressure, were identified in patients with Krabbe disease. Although difficult to assess, our study highlights the importance of monitoring for increased intracranial pressure, which can result in spontaneous third ventriculostomies, in patients with infantile Krabbe disease.

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Section: Patients Without Stv Patients With Stvmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Spontaneous Third Ventriculostomy in Krabbe Disease

Zuccoli

Kim

Poe

et al. 2020

Pediatric Neurology

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“…The two patients inherited this mutation from their father, who was heterozygous for the mutation. Interestingly, this mutation was reported in another patient with adult-onset, although no vision loss was reported [10,22] . The phenotype and genotype for the Krabbe disease shows considerable variation worldwide, which thereby rendering difficulty in accurate diagnosis [23] .…”

Section: Discussionmentioning

confidence: 99%

GALC mutations in Chinese patients with late-onset Krabbe disease: a case report

Zhuang

Kong

et al. 2019

Preprint

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Background: Krabbe disease (also known as globoid cell leukodystrophy) is an autosomal recessive neurodegenerative disorder caused by a deficiency of the enzyme -galactocerebrosidase (galactosylceramidase, GALC). The deficiency of GALC leads to accumulation of galactosylceramide and psychosine, the latter GALC substrate having a potential role in triggering demyelination. Typically, the disease has an infantile onset, with rapid deterioration in the first few months, leading to death before the age of 2 years. The late onset forms (late-infantile, juvenile, and adult forms) are rare with variable clinical outcomes, presenting spastic paraplegia as the main symptom. Case presentation: We recruited a family with two affected individuals. The proband (Patient 1), a 25-year-old male, was presented with slow progressive spastic gait disturbance and vision loss, suffering since the 5th year of life. His elder sister (Patient 2), became wheelchair-bound and demented at the age of 22 years. Brain magnetic resonance imaging (MRI) showed increased signal intensity in the white matter along with the involvement of the bilateral corticospinal tracts. GALC deficiency was confirmed by biochemical analysis. DNA sequencing revealed two mutations (c.865G>C: p. G289R and c.136G>T: p. D46Y) in GALC. The clinical characteristics, brain MRI, biochemical and molecular findings led to the diagnosis of Krabbe disease. Conclusion: Clinical and neuroimaged signs, positive enzymatic analysis and molecular data converged to definite diagnosis in this neurodegenerative disease.

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“…7,28 This genetic lesion was not noted in KD Japanese patients, instead, they show c.683_694del12insCTC or c.2002A > C (635_646del12insCTC and 1954A > C), representing approximately 30% of Japanese EIKD-associated alleles. 29 Recently, Liao et al 30 found that the symptoms of KD were heterogeneous across all ages of KD patients. EIKD was found to be the most prevalent form of KD among the Muslim Arabs and Druze communities, mostly due to the homozygous occurrence of two mutations: c.1582G > A (p.D528N) and c.1748 T > G (p.I583S), respectively.…”

Section: Introductionmentioning

confidence: 99%

Krabbe Disease in the Arab World

Zayed

2015

J Pediatr Genet

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The autosomal recessive inherited Krabbe disease (KD) is a devastating pediatric lysosomal storage disorder affecting white matter of the brain. It is caused by mutations in the gene coding for the lysosomal enzyme galactocerebrosidase. While most patients present with symptoms within the first 6 months of life, others present later in life throughout adulthood. The early infantile form of KD (EIKD) is frequent in the Muslim Arab population in Israel, with a very high prevalence of approximately 1/100 to 1/150 live births. The homozygous variant c.1582G > A (p.D528N) was found to be responsible for EIKD in Palestinian Arab patients. KD was reported in different Arab countries with much lower frequency. While most Arab patients presented with EIKD, late infantile and late onset KD forms were also reported. Most Arab patients presented with variable symptoms ranging from EIKD to late onset KD, with variable clinical findings. Based on literature studies, this review focuses on the clinical and molecular findings of KD patients with Arab ancestry, and highlights the need for developing universal genetic screening programs to overcome the under-reported status of KD prevalence in Arabia. This is expected to improve the prognosis of the disease and promote targeted molecular diagnostics to the Arab patients.

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Phenotypic Variability of Krabbe Disease Across the Lifespan

Cited by 24 publications

References 57 publications

Spontaneous Third Ventriculostomy in Krabbe Disease

Spontaneous Third Ventriculostomy in Krabbe Disease

GALC mutations in Chinese patients with late-onset Krabbe disease: a case report

Krabbe Disease in the Arab World

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