Republic of the Philippines

CARAGA
STATE UNIVERSITY

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P.O. Box 165, Ampayon, 8600 Butuan City,
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www.carsu.edu.ph

 

 

 

 

 

 

 

 

 

 

 

General Biology 2 –
Galilie

 

 

 

 

 

 

 

 

 

 

Florence Jhun F.
Almadin

 

 

 

 

 

 

 

 

 

 

Cyrel O. Layson

January
24,2018
 INTRODUCTION

Sickness unpredictably influences
individuals of any age, from the earliest appearances of inborn genetic
disorders in infants, to the late-beginning neurodegenerative conditions that
torment our old generation.In
1916, The Krabbe Disease
was discovered in Denmark by a Danish specialist Knud Krabbe.  Knud discovered the disease when he saw that
kids were crying for no reason and were having some other symptoms for no
reason. (Adhit S 2014 ).. Krabbe disease (galactosylceramide lipidosis) is a
quickly dynamic demyelinating issue of newborn children caused by lacking
movement of the chemical galactosylceramide ?-galactosidase (Wenger et.al.,
2007). This type of disease also happen in adults .Transmission is via
autosomal passive legacy, and the quality maps to chromosome 14.
Galactosylceramide is put away inside multinucleated macrophages of the white
matter of the focal sensory system, shaping globoid cells. Later on,Collier and Greenfield (1924)  used
the term globoid to describe these abnormal scavenger cells,
which are characteristic for this disorder.  In 1970  (Malone,Suzuki ,Sazuki)  reported
that tissue samples from patients with Krabbe
disease could not degrade galactosylceramide due to a deficiency of
galactocerebrosidase (GALC) activity. Galactosylceramide is produced during the
lysosomal degradation of sulfatide. These two glycosphingolipids are important
for healthy, stable myelin. The measurement of GALC activity in leukocytes,
fibroblasts, and fetal-derived cells can identify patients with Krabbe disease both postnatally and
prenatally.Few years after discovery many experimental animal models of
globoid cell leukodystrophy are used.They are helpful to research the compound
pathogenesis of GALC lack and to investigate techniques for successful
treatment. In addition , the mouse and dog models have been utilized for
quality treatment trials, neural undeveloped cell transplantation, , substrate
decrease treatment, and cytokine infusions, alone or in various combination.
While no medications have brought about a “cure,” a few medicines
have lead to a significant extension of the lives of the treated animals.(Rafi
M.A 2016)

 

PATHOPHYSIOLOGY

             Krabbe disease or globoid cell leukodystrophy (GLD), is an autosomal
recessive disorder resulting from a deficiency in an enzyme known as
galactocerebrosidase (GALC). This enzyme is responsible for the
degradation of galactocerebroside to ceramide and of galactosylsphingosine,
otherwise called psychosine to sphingosine. Galactocerebroside is a major
component of myelin (Haddad R.S 2017).Myelin isn’t unusual in these people,
however the protein insufficiency causes a problem in substrates.

 During the first 18 months of life this is
particularly critical when myelin development and turnover are high. It is the
increased galactosylsphingosine levels that are toxic and lead to the
destruction of oligodendroglia and impaired Schwann cell function in the CNS
and to demyelination. The undegraded substrates accumulate in multinucleated
macrophages in demyelinated regions of the brain. These “globoid”
cells portray this ailment, which is otherwise called globoid cell
leukodystrophy (Wenger D., Luzi P. 2014)

Krabbe disease wrecks
those myelin sheaths of the central and the peripheral nervous system. Those
enzyme galactocerebroside ?-galactosidase regularly removes galactose from
galactosylceramide (galactocerebroside, a complex glycosphingolipid), which is
a major component of the myelin sheath.  When the enzymatic degradation is
blocked, galactocerebroside accumulates inside hematogenous macrophages, the
globoid cells, which are the microscopic hallmark of the disease in brain
tissue. A second galactose-containing compound, galactosphingosine
(psychosine), is also a substrate for the enzyme. When the enzyme is missing,
psychosine concentration is increased. Psychosine is toxic to oligodendrocytes,
the cells that build and support the myelin membranes. (Tsuji S.2007)

Krabbe disease is very rare.
According to the Mayo Clinic, the disease affects about 1 in every 100,000
people in the United States. It occurs most frequently in people of
Scandinavian descent. A child has a one in four chance of developing the
disorder if both parents have the defective gene. (Cafasso J. Kim S 2016)

 

CLINICAL MANIFESTATION

             Infantile Krabbedisease, the most frequently encountered form,
is a dramatic disease that strikes young, healthy-looking infants and leads to
profound disability within a few months (Hagberg et al., 1970). The disease
begins acutely at 4–6 months of age the hallmark symptoms of the infantile form include restlessness, progressive stiffness, irritability, hypersensitivity,
psychomotor arrest and hypertonia. This is followed by rapid mental and motor
deterioration, seizures and optic atrophy. Death usually ensues within the
first two years of life and there is currently no cure (Davenport et.al 2011).

 Convulsions can grow however are not really of an
epileptic nature. They may rather speak to tonic fits that seem excruciating
and are actuated by outer boosts, for example, touch, sudden splendid light, or
noise. It is critical for administration to perceive this kind of seizure-like
conditions, as they don’t react to anticonvulsive medications. An eruption to
commotion, for example, being startled has been named hyperacusis. Deafness may
happen .Optic atrophy is frequently seen. The infants show increased muscular
tone, with few spontaneous movements. Muscle stretch reflexes are difficult to
elicit and can be absent. The combination of signs pointing to the first motor
neuron (spasticity) and in the mean time to the second motor neuron (loss of
reflexes) is a clue to the presence of a systemic disorder affecting the myelin
sheaths of the central and the peripheral nervous system. Terminally, infants
are flaccid and develop bulbar signs. Life expectancy is barely more than 2
years. ( Kohlschütter A. ,2013)

Late-beginning
types of Krabbe illness may show themselves in adolescence or in adulthood, the
real extent in the vicinity of 3 and 10 years old, however a few patients have
been solid into their forties or even up to the age of 60. While more uncommon
than the juvenile shape, they are as a rule progressively perceived through the
utilization of neuroimaging methods and enzymatic or sub-atomic hereditary
testing (Kolodny et al., 1991; De Gasperi et al., 1999; Wenger et al., 2001).
In late-beginning cases, neurological indications most usually incorporate a
gradually developing spastic paraparesis. Less regularly the dominating side
effects incorporate an engine and tangible neuropathy, hemiparesis, cerebellar
ataxia, or cortical visual deficiency. Scholarly capacities may stay unaffected
for a long time. Most patients with late-beginning structures have indicated
fast decay at first, trailed by a more slow movement going on for quite a
while. At times a patient’s condition appeared to settle and even make strides.
What’s more, noteworthy interfamilial inconstancy of clinical discoveries has
been found in a few families. Such perceptions make it hard to assess the
viability of potential new medicines in late-beginning patients (Lim et al.,
2008).

 

MEDICAL MANAGEMENT

            There is no cure for Krabbe disease. In any case, the the
following treatments might be given to patients to help reduce their side
effects such as anticonvulsant prescription to stop seizures, muscle relaxer
drugs (to enable straightforwardness to muscle spasms),physical treatment to
assist moderate crumbling of muscles,occupational treatment with helping more
seasoned youngsters with regular errands, for example, getting dressed and
eating .

Research
has discovered two methods that may affect the movement of Krabbe disease, as
opposed to simply treating the side effects: bone marrow transplantation and
line blood transplantation.Durig this procedure, a man with Krabbe disease  receives cells from a healthy person . The
new cells can make the GALC enzyme that the patient couldn’t make his or her
own. Both of these strategies have dangers of their own. ( Prasad V.K. ,
Kurtzberg J.,2009)

In bone marrow transplantation an adult will donate some bone marrow (a material found
in bones) to replace the bone marrow in the child who has Krabbe disease. The
best results have been only in patients with late-onset Krabbe disease who have
been treated before severe symptoms develop. It has not been helpful in infants
with early-onset Krabbe disease who have already developed symptoms.On the
other hand ,in the cord blood transfusion a doctor will transfuse cord blood
stem cells into the patient. The cells are taken from the umbilical cord of a
donor who is not related to the patient. However, this procedure has also been
shown to help only those patients treated before symptoms appear.( Prasad
V.K. , Kurtzberg J., 2009)

 

REFERENCES

Electronic Sources / Basic format (Internet
sites)

1
Adhit S (2014 March 10). Krabbe
Disease/Globoid Cell Leukodystrophy.Retrieved

fromhttps://prezi.com/e-op_vruqysp/krabbe-diseasegloboid-cell-leukodystrophy/

                           7 Haddad R.S (2017).
Krabbe Disease,medscape.Retrived from

                                       https://emedicine.medscape.com/article/951722-overview

12 Kohlschütter A. (2013 ).Lysosomal leukodystrophies: Krabbe disease and metachromatic leukodystrophy.Retrived
from

 https://www.sciencedirect.com/science/article/pii/B9780444595652000290

6
Rafi M.A (2016 June15).Gene therapy for
CNS diseases – Krabbe disease.Retrived from

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981250/

https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/krabbe-disease

 

9Tsuji S.(2007,September 28).Neurobiology of
disease.Retrived from

https://www.sciencedirect.com/science/article/pii/B9780120885923500062

 

Electronic Sources/ Multiple Authors(Internet
Sources)

10
Cafasso J. Kim S (2016, January 20). Krabbe Disease: Causes, Symptoms &
Diagnosis.Retrieved from

https://www.healthline.com/health/krabbe-disease

3
Collier,Greenfield (1924). Globoid cell leukodystrophy. Retrived from http://www.medlink.com/article/globoid_cell_leukodystrophy

11
Davenport et.al(2007).Competing on
Analytics: The New Science of Winning.Retrived from https://www.researchgate.net/publication/275712863_Competing_on_Analytics_The_New_Science_of_Winning

 

13Kolodny ,De Gasperi, Wenger (2001).Genetics of primary progressive multiple
sclerosis.Retrived from https://www.sciencedirect.com/science/article/pii/B9780444595652000290

14
Lim et.al (2008).Stem Cell
Transplantation for Adult-Onset Krabbe Disease: Report of a Case.Retrived
from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3755578/

4,5
Malone,Suzuki(1970). Globoid cell leukodystrophy. Retrived from

http://www.medlink.com/article/globoid_cell_leukodystrophy

15
16  Prasad V.K. , Kurtzberg J.( 2009,
November 16 ).Cord blood and bone marrow
transplantation in inherited.Retrived from  http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2009.07974.x/pdf

2 Wenger
et.al. (2007). A Microglial Hypothesis of Globoid Cell Leukodystrophy
Pathology. Retrieved from

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027969/

8
Wenger D., Luzi P.( 2014,November 7).Krabbe Disease: Globoid Cell
Leukodystrophy.Retrived from

https://www.sciencedirect.com/science/article/pii/B9780124105294000309

 

Journal,References,Magazines,ect.

Wenger,
D. A., Suzuki, K., Suzuki, Y. and Suzuki, K.(2001). Galactosylceramide
Lipidosis: Globoid Cell Leukodystrophy (Krabbe Disease), pp. 3669-3694.