Krabbe Disease: An Overview of a Rare Genetic Neurodegenerative Disorder
Published: 2022-10-07
Page: 132-139
Issue: 2022 - Volume 5 [Issue 1]
Adedeji Okikiade *
College of Medicine, All Saints University, Saint Vincent and the Grenadines. b Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria.
Miriam Tikanide
College of Medicine, All Saints University, Saint Vincent and the Grenadines. b Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria.
Esther Akinyode
College of Medicine, All Saints University, Saint Vincent and the Grenadines. b Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria.
Annah Akoth
College of Medicine, All Saints University, Saint Vincent and the Grenadines. b Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria.
Olayinka Oloye-Afolayan
College of Medicine, All Saints University, Saint Vincent and the Grenadines. b Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria.
Damisola Ogunesan
College of Medicine, All Saints University, Saint Vincent and the Grenadines. b Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria.
*Author to whom correspondence should be addressed.
Abstract
Krabbe disease (or Globoid cell leukodystrophy) is a rare mutation of a gene found on chromosome 14q31 responsible for the production of the enzyme called galactocerebrosidase (G ALC), which breaks down two galactolipids; galactosyl-ceramide and galactosylsphingosine (psychosine) found in the central nervous system (CNS). This enzyme's absence causes some substrate buildup, particularly psychosine.
Krabbe disease (KD) results from the toxicity of psychosine in the central nervous system, leading to clinical manifestations that characterize the disease. Demyelination occurs due to these cytotoxic activities of psychosine, leading to severe neuronal damage and the formation of globoid cells. Most cases present with fatal clinical manifestations and a bad prognosis.
The incidence in the United States is approximately 1:100,000 but could be more in certain parts of the country. The incidence is higher in males. The mode of inheritance is primarily autosomal. Diagnosis is best confirmed by the fibroblast's qualitative and quantitative analysis of the enzyme galactocerebrosidase (galactosylceramidase).
This disease has no cure. Numerous research works showed that cases presented earlier could be treated with HSCT to bring about more favorable outcomes. The use of low-dose morphine may help with irritability common in these patients. This review article aims to achieve a basic understanding of this rare neurological disorder among medical and health professionals/students.
Keywords: Krabbe disease, galactocerebrosidase (GALC), lipids, globoid cell leukodystrophy, autosomal recessive
How to Cite
References
Krabbe disease. National Institutes of Health. Krabbe Disease | National Institute of Neurological Disorders and Stroke (nih.gov); 2022.
Jain M, De Jesus O. Krabbe Disease. In: StatPearls. Treasure Island (FL): StatPearls Publishing; September 18, 2021.StatPearls Publishing; 2022. Available:https://www.ncbi.nlm.nih.gov/books/NBK562315/
Cleland WW, Kennedy EP. The enzymatic synthesis of psychosine. J Biol Chem. 1960;235:45-51.
Li, Y; Sands, MS. "Experimental therapies in the murine model of globoid cell leukodystrophy." Pediatric Neurology (Review). 2014;51(5):600–6.
DOI:10.1016/j.pediatrneurol.2014.08.003. PMC 4252788
PMID 25240259
Synd/1457 at Who Named It?. http://www.whonamedit.com/synd.cfm/1457.html
Graziano, Adriana & Cardile, Venera. History, genetics, and recent advances on Krabbe disease. Gene. 2014;555.
DOI: 10.1016/j.gene.2014.09.046.
Mayo Clinic Staff: “Krabbe Disease." Mayo Clinic; 2018. Available: https://en.wikipedia.org/wiki/Krabbe_disease.
Matsuda Junko, Suzuki Kunihiko Barranger, John A. Cabrera-Salazar, Mario A. (eds.), "Krabbe Disease (Globoid Cell Leukodystrophy)," Lysosomal Storage Disorders, Springer US. 2007;269– 283.
DOI: 10.1007/978-0-387-70909-3_18
ISBN: 9780387709093 Books.Google.com
Amin Mutaz, Elsayad Liena, Ahmed Ammar Eltahir. Clinical and Genetic Characteristics of Leukodystrophies in Africa. Journal of Neurosciences in Rural Practice. 2017;8(S 01):S089–S093.
DOI: 10.4103/jnrp.jnrp_511_16
PMC: 5602269. PMID 28936078.
Jalal K, Carter R, Yan L, Barczykowski A, Duffner PK. Does galactocerebrosidase activity predict Krabbe phenotype? Pediatr Neurol. 2012;47:324–329. DOI: 10.1016/j.pediatrneurol.2012.07.003.
Langan Thomas J. Krabbe disease. Up To Date; 2016. Retrieved 18 October 2018.
Kohlschütter A. Lysosomal leukodystrophies: Krabbe disease and metachromatic leukodystrophy. Handb Clin Neurol. 2013;113:1611-1618.
DOI: 10.1016/B978-0-444-59565-2.00029-0
ISBN: 9780444595652. PMID: 23622382.
Turgeon CT, Orsini JJ, Sanders KA, Magera MJ, Langan TJ, Escolar ML, Duffner P, Oglesbee D, Gavrilov D, Tortorelli S, Rinaldo P, Raymond K, Matern D. Measurement of psychosine in dried blood spots--a possible improvement to newborn screening programs for Krabbe disease. J Inherit Metab Dis. 2015; 38(5):923-9.
Hawkins-Salsbury JA, Parameswar AR, Jiang X, et al. Psychosine, the cytotoxic sphingolipid that accumulates in globoid cell leukodystrophy, alters membrane architecture. J Lipid Res. 2013;54(12): 3303-3311. DOI:10.1194/jlr.M039610
Spratley SJ, Hill CH, Viuff AH, Edgar JR, Skjødt K, Deane JE. Molecular Mechanisms of Disease Pathogenesis Differ in Krabbe Disease Variants. Traffic. 2016;17(8):908-922. DOI:10.1111/tra.12404
Orsini JJ, Escolar ML, Wasserstein MP, et al. Krabbe Disease. 2000 Jun 19 [Updated 2018 Oct 11]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022.
Hussain SA, Zimmerman HH Abdul-Rahman OA, Hussaini SM, Parker CC, Khan M. Optic Nerve Enlargement in Krabbe Disease: A Pathophysiologic and Clinical Perspective. Journal of Child Neurology. 2011;26(5):642–644.
DOI:10.1177/0883073810387929.
PMID 21285037
S2CID 22242663.
Zayed H. Krabbe Disease in the Arab World. J Pediatr Genet. 2015;4(1):1-8. DOI:10.1055/s-0035-1554981
Escolar ML, Kiely BT, Shawgo E, Hong X, Gelb MH, Orsini JJ, Matern D, Poe MD. "Psychosine, a marker of Krabbe phenotype and treatment effect." Molecular Genetics and Metabolism. 2017;121(3): 271–278. DOI:10.1016/j.ymgme.2017.05.015.
ISSN 1096-7192
PMC 5548593
PMID 28579020.
Minter Baerg MM, Stoway SD, Hart J, Mott L, Peck DS, Nett SL, Eckerman JS, Lacey JM, Turgeon CT, Gavrilov D, Oglesbee D, Raymond K, Tortorelli S, Matern D, Mørkrid L, Rinaldo P. Precision newborn screening for lysosomal disorders. Genet Med. 2018; 20:847–54.
Orsini Joseph J, Kay Denise M, Saavedra-Matiz, Carlos A, Wenger David A, Duffner, Patricia K, Erbe Richard W, Biski Chad, Martin, Monica Krein Lea M, Nichols, Matthew; Kurtzberg, Joanne. "Newborn screening for Krabbe disease in New York State: the first eight years experience." Genetics in Medicine. 2016;18(3):239–248.
DOI:10.1038/gim.2015.211
ISSN 1530-0366
PMID 26795590.
Jain M, De Jesus O. Krabbe Disease. [Updated 2021 Sep 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022.
Available:https://www.ncbi.nlm.nih.gov/books/NBK562315/
Suzuki K, Suzuki Y. Globoid cell leucodystrophy (Krabbe's disease): deficiency of galactocerebroside beta-galactosidase. Proc Natl Acad Sci USA. 1970;66(2):302-9.
Orsini JJ, Escolar ML, Wasserstein MP, Caggana M. Krabbe Disease. In: Adam MP, Everman DB, Mirzaa GM, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; June 19, 2000. [updated 2018 Oct 11]
Shah Samir S, Ebberson Jessica, Kestenbaum Lori A, Hodinka Richard L, Zorc Joseph J. "Age-Specific Reference Values for Cerebrospinal Fluid Protein Concentration in Neonates and Young Infants. Journal of Hospital Medicine. 2011;6(1):22–27.
DOI:10.1002/jhm.711.
ISSN 1553-5592
PMC 2978786
PMID 20629018
Cannizzaro LA, Chen YQ, Rafi MA, Wenger DA. Regional mapping of the human galactocerebrosidase gene (GALC) to 14q31 by in situ hybridization. Cytogenet Cell Genet. 1994; 66(4):244-245.
DOI: 10.1159/000133703