Sphingolipidosis

1. Sphingolipidosis
Speaker: Shao-Wei Chao 17/01/2023

2. 1 Introduction
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3. Introduction
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is a collective term for the various metabolic disorders due to an
abnormal sphingolipid metabolism.
It is one of the many different types of lysosomal disease.
It is also a class of lipid storage disorders.
Sphingolipidosis

4. 2 Diseases
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Tay–Sach's disease
A genetic mutation in the HEXA gene on chromosome 15, which
codes for a subunit of the hexosaminidase enzyme
hexosaminidase A (hex-A) that results in a failure to process GM2
ganglioside that accumulates in the brain and other tissues.
Diseases
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Tay–Sach's disease
Types:
• 1. Infantile TSD
• 2. Juvenile TSD
• 3. Adult/ late onset TSD
Diseases
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Syptoms:
• 1. Infantile TSD: deafness, progressive blindness,
decreased muscle strength, increased startle response,
paralysis or loss of muscle function, seizure, muscular
stiffness, delayed mental and social development, slow
growth, red spot on the macula.
• 2. Juvenile TSD: muscle weakness, seizures, and
recurring respiratory infections.
• 3. Adult/ late onset TSD: muscle weakness, slurred
speech, unsteady gait, memory problems, tremors.

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 Treatment:
There is no cure for Tay–Sachs disease.
 However there are ways of making their lives comfortable:
1) Massage therapy
2) Feeding tubes
3) Wheel chairs, canes, and walkers
Diseases
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Tay–Sach's disease

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Fabry disease
A deficiency of alpha galactosidase A (a-GALA) due to mutation
causes globotriaosylceramide to accumulate within the blood
vessels, other tissues, and organs.
Diseases
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Fabry disease
Types:
• 1. Classic type
• 2. Late-onset/atypical type
Diseases
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Syptoms:
• 1. Classic type: A painful burning sensation in
the hands and feet.
• 2. Late-onset/atypical type: People with late-
onset Fabry disease don’t have symptoms until
they’re in their 30s or older. The first indication
of a problem may be kidney failure or heart
disease.

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Fabry disease
 Treatment:
• Enzyme replacement therapy
is designed to provide the enzyme the patient is missing as a result of a genetic
malfunction. This treatment is not a cure, but can partially prevent disease progression,
and potentially reverse some symptoms.
• Organ-specific treatment
Pain associated with Fabry disease may be partially alleviated by enzyme replacement
therapy in some patients, but pain management regimens may also include analgesics,
anticonvulsants, and nonsteroidal anti-inflammatory drugs, though the latter are usually
best avoided in kidney disease.
Diseases
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Gaucher disease
A hereditary deficiency of the enzyme glucocerebrosidase, which
acts on glucocerebroside. When the enzyme is defective,
glucocerebroside accumulates, particularly in white blood cells
and especially in macrophages. Glucocerebroside can collect in
the spleen, liver, kidneys, lungs, brain, and bone marrow.
Diseases
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Gaucher disease
Types:
• 1. Type I
(N370S homozygote)
• 2. Type II
(one or two alleles L444P)
• 3. Type III
(one or two copies of L444P,
possibly delayed by
protective poly-morphisms)
Diseases
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Syptoms:
• 1.Type I: Impaired olfaction and cognition.
• 2. Type II: Serious convulsions, hypertonia,
intellectual disability, and apnea.
• 3. Type III: Muscle twitches known as myoclonus,
convulsions, dementia, and ocular muscle apraxia.

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Gaucher disease
 Treatment:
• Enzyme replacement therapy
For those with type-I and most type-III, enzyme replacement
treatment with intravenous recombinant glucocerebrosidase can
decrease liver and spleen size, reduce skeletal abnormalities, and
reverse other manifestations.
• Alglucerase(drug)
A version of glucocerebrosidase that was harvested from human
placental tissue and then modified with enzymes.
Diseases
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Niemann-Pick disease
Mutations in the SMPD1 gene cause Niemann–Pick disease types
A and B. They produce a deficiency in the activity of the
lysosomal enzyme acid sphingomyelinase, that breaks down the
lipid sphingomyelin.
Diseases
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Niemann-Pick disease
Types:
• 1. TypeA
• 2. Type B
• 3. Type C
• 4. TypeE
Diseases
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Syptoms:
Syptoms are related to the organs in which
sphingomyelin accumulates.
Enlargement of the liver and spleen may
cause reduced appetite, abdominal
distension, and pain.
Enlargement of the spleen may also caus
low levels of platelets in the blood.

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Niemann-Pick disease
 Treatment:
• TypeA
No specific treatment.
• TypeB
Physicians try to keep cholesterol levels down to normal levels. If
statins are used, they monitor liver function. If the spleen is
enlarged and platelet levels low, acute episodes of bleeding may
require transfusions of blood products. If they have symptoms of
interstitial lung disease, they may need oxygen.
Diseases
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References
1) https://en.wikipedia.org/wiki/Sphingolipidoses
2) https://en.wikipedia.org/wiki/Tay%E2%80%93Sachs_disease
3) https://pt.slideshare.net/quelz/tay-sachs-disease- 30289828?ref=
4) https://www.healthline.com/health/tay-sachs- disease#symptoms
5) https://en.wikipedia.org/wiki/Fabry_disease
6) https://my.clevelandclinic.org/health/diseases/16235-fabry-disease
7) https://en.wikipedia.org/wiki/Gaucher%27s_disease
8) https://en.wikipedia.org/wiki/Niemann%E2%80%93Pick_disease
9) https://www.healthline.com/health/niemann-pick-disease#symptoms
Diseases
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18. Thanks for your participation
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