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Krabbe disease/galactosylceramide lipidosis/globoid cell leukodystrophy
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
In classic Krabbe disease and its variants, neuroimaging usually indicates diffuse cerebral atrophy [44–46]. The scan may be normal early in the disease [47]. Diffuse hypodensity of the white matter has also been described [48]. Plaque-like high intensity T2 signal has been observed in periventricular and cerebellar white matter in three patients [49].
DTI of Developmental and Pediatric Disorders
Published in Andrei I. Holodny, Functional Neuroimaging, 2019
Michael J. J. Kim, James M. Provenzale
Globoid cell leukodystrophy, also known as Krabbe disease, is an autosomal recessive white matter disorder caused by the deficiency of β-galactocerebrosidase (26). In the normal brain, galactolipids that are toxic to brain tissue are formed during white matter myelination but are quickly hydrolyzed by the enzyme β-galactocerebrosidase. However, in Krabbe disease, diminished levels of this enzyme allow galactolipids to accumulate and myelin-forming oligodendroglia are destroyed. In early-onset Krabbe disease, this leads to the failure of normal myelin production in infants and subsequent development of severe neurological deficits (27). These children typically deteriorate neurologically until they reach a vegetative state and ultimately die within two to four years. Hematopoietic stem cell transplantation has been suggested as a treatment for asymptomatic infantile Krabbe disease (28). There are currently no proven therapeutic options for symptomatic patients with the infantile form of Krabbe disease. Therefore, early diagnosis of the disease is critical for any treatment to be effective.
Genetic diseases mimicking multiple sclerosis
Published in Postgraduate Medicine, 2021
Chueh Lin Hsu, Piotr Iwanowski, Chueh Hsuan Hsu, Wojciech Kozubski
Krabbe disease, also known as globoid cell leukodystrophy, is a rare autosomal recessive leukodystrophy caused by deficient galactosylceramidase (GALCase) activity as a result of mutations in the GALC gene. The resulting unmetabolized galactolipids build up and are directly toxic to oligodendrocytes and Schwann cells, which manifests as progressive neurodegenerative symptoms including loss of vision, hearing, seizures, and premature death [73]. The newborn initial screening test of GALC enzyme activity is usually conducted to detect Krabbe disease. However, low levels of GALC enzyme activity cannot indicate the clinical type and the course of the disease. The genetic testing of Krabbe disease should be taken to confirm the diagnosis [73]. The four clinical types are classified by the age of onset [74], of which adult- onset Krabbe disease (AOKD) is of particular interest in this discussion due to its similar clinical pictures to MS [75].
A new compound heterozygous mutation in adult-onset Krabbe disease
Published in International Journal of Neuroscience, 2020
Xianghe Meng, Yingjiao Li, Yajun Lian, Yujuan Li, Liyuan Du, Nanchang Xie, Cui Wang
Krabbe disease (KD), also known as globoid cell leukodystrophy, was first described by the Danish neurologist, Knud Krabbe, in 1916 [1]. KD is characterized by extensive demyelination, axonal injury and the formation of multinucleated macrophages (globoid cell) [2]. KD can be divided into four different forms, which could be distinguished based on the age at onset of neurological symptoms: early-onset or early infantile (onset in the first 6 months), late-onset, including late infantile (onset 6 months to 3 years), juvenile (onset 3‐8 years), and adult (≥9 years) [3]. The prevalence of Krabbe disease is 1/100,000‐1/250,000 [4,5], with the early infantile and late infantile forms accounting for 85–90% of cases. The late-onset adult form is clinically rare with a prevalence of less than 1 in a million [6] and it exhibits heterogenous clinical features [7]. Therefore, the diagnosis of adult-onset KD is challenging and often delayed.
Digital microfluidics comes of age: high-throughput screening to bedside diagnostic testing for genetic disorders in newborns
Published in Expert Review of Molecular Diagnostics, 2018
David Millington, Scott Norton, Raj Singh, Rama Sista, Vijay Srinivasan, Vamsee Pamula
NBS for LSDs, a group of approximately 40 IMDs that were not previously accessible to NBS, gained momentum in the early 2000s with the development of fluorometric enzymatic assays including alpha-iduronidase (IDUA), alpha-galactosidase (GLA) and acid alpha-glucosidase (GAA), the enzymes deficient in Hurler Syndrome (MPS I), Fabry Disease and Pompe Disease (GSD-II), respectively [6–8]. The development of enzyme replacement therapies for these and other LSDs generated even more interest in NBS to find patients that could most benefit from early treatment [5]. Accordingly, NBS for Pompe disease started in Taiwan, which has a relatively high incidence of this LSD compared with other ethnic groups, using an adaptation of the benchtop microfluorometric assay [34]. Results showed convincingly that NBS for LSDs was viable, and outcomes for cases of infantile Pompe disease were much better when treatment was provided soon after birth [35,36]. In the meantime, a method to screen for galactosylceramidase (GALC), the enzyme deficient in Krabbe disease, using MS/MS with a non-fluorogenic synthetic substrate, was introduced [9]. Cases of early onset Krabbe disease reportedly were treated successfully by bone marrow transplantation [37] and the family of one such case subsequently lobbied successfully to introduce NBS for Krabbe in New York State.