Name: Gaucher Disease
Uploaded: 2021-12-14
Duration: 7 min 45 s
Description: . . BIOL2109 BIOCHEMISTRY OF METABOLISM. INBORN ERRORS OF METABOLISM - VIDEO PRESENTATION.

. . BIOL2109 BIOCHEMISTRY OF METABOLISM. INBORN ERRORS OF METABOLISM - VIDEO PRESENTATION. 

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INBORN ERRORS OF METABOLISM - VIDEO PRESENTATION

Tadgh Dulohery, Kate Farrell McCabe, Tara Howley, Ciara Keenan

. . OBJECTIVES. Aetiology and Metabolic Pathways. 

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Policies and Guidelines relating to Gaucher Disease

. . GAUCHER DISEASE -
WHAT IS IT?. Gaucher’s disease is an autosomal recessive lysosomal storage disorder (National Gaucher Foundation, 2021). 

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Gaucher’s disease is an autosomal recessive lysosomal storage 
disorder (National Gaucher Foundation, 2021)

It is also classified as a lipid storage disorder and thus, results in 
the accumulation of fatty substances in cells.

It is caused by a mutation in the acid-beta-glucosidase gene 
(GBA1) which translates into low levels of the enzyme 
glucocerebrosidase

Type 1: non-neuronopathic Gaucher’s disease

Type 2: acute neuronopathic Gaucher’s disease

Type 3: chronic neuronopathic Gaucher’s disease

There is also a perinatal-lethal form and a cardiovascular form 
(National Organisation of Rare Disorders, 2018)

Autosomal Recessive
Parents
Children
1

There are three types
of Gaucher disease'
Type I (94%)
— only *wolves
the internd organs and not the
rEtvous system*
Type 2
Affets ttE central system;
Type 3 (SY.)
Affcts central nevow systan a-vd
internal orgms•.

. . Gaucher’s disease is characterised by deficiency of the enzyme glucocerebrosidase.. 

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Gaucher’s disease is characterised by deficiency of the enzyme glucocerebrosidase.

This enzyme is required for breakdown of glycosphingolipids

It specifically catalyses the breakdown of glucosylceramide to glucose and ceramide in the lysosome.

In absence or when lacking this enzyme, this reaction cannot occur.

Consequently, glucosylceramide and its derivatives accumulate in the lysosomes of macrophages. 
These lipid-laden cells are known as ‘Gaucher cells’.

10
OH
HO
10
10
GlucosylCeramide
OH
GCase
HO
Glucose
Ceramide

. . WHAT HAPPENS NEXT?. . Accumulation of glycosphingolipids affects important cell functions like:. 

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Accumulation of glycosphingolipids affects important cell 
functions like:

Gaucher cells also release various cytokines such as 
interleukin 1 and tumour necrosis factor which creates a pro-
inflammatory environment (Thomas. AS et al, 2014)

Furthermore, low levels of this enzyme causes fatty deposits in 
various organs and bones causing them to enlarge (Mayo Clinic, 
2020)

. . SYMPTOMS. When lipids accumulate in certain organs, such as spleen or liver — gives rise to symptoms (Stirnemann J, et al., 2017). Symptoms vary from person to person- can be asymptomatic throughout life or experience severe complications. 

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When lipids accumulate in certain organs, such as spleen or liver — gives rise to symptoms (Stirnemann J, et al., 2017).
Symptoms vary from person to person- can be asymptomatic throughout life or experience severe complications

When lipids accumulate in certain organs, such as spleen or liver – gives rise to symptoms (Stirnemann J, et al., 2017).

Symptoms vary from person to person- can be asymptomatic throughout life or experience severe complications

•
Osteoporosis and fracture 
risk (National Organisation for Rare

•
Glucocerebrosides accumulate in 
liver + spleen – abnormal blood 
counts / blood cell production

•
Low platelet levels - bleeding 
problems and easy bruising

. . SYMPTOMS - TYPE 2. Type 2 and 3 — neuropathic Gaucher disease, early onset brain involvement that worsens as disease progresses. Type 2 occurs in newborns and infants — symptoms occur within first 3 to 6 months of life Death usually occurs between ages 1 and 3 (National Gaucher Foundation).. 

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Type 2 and 3 — neuropathic Gaucher disease, early onset brain involvement
that worsens as disease progresses.
Type 2 occurs in newborns and infants — symptoms occur within first 3 to 6 months of life
Death usually occurs between ages 1 and 3 (National Gaucher Foundation).

Type 2 and 3 – neuropathic Gaucher disease, early onset brain involvement 
that worsens as disease progresses.
Type 2 occurs in newborns and infants – symptoms occur within first 3 to 6 months of life
Death usually occurs between ages 1 and 3 (National Gaucher Foundation).

Feeding difficulties –
difficulty sucking and

Enlarg«f spleen and liver
(hepatospmomegaly)
Liver
Spleen

. . SYMPTOMS. -TYPE 3. - Same symptoms as type 1 (hepatosplenomegaly, blood disorders) plus neurological complications Neurological complications in type 3 - lower/ gradual onset than type 2 (National Gaucher Foundation) - Patients with type 3 survive into adulthood or later life (National Organisation for Rare Diseases). 

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- Same symptoms as type
1 (hepatosplenomegaly, blood
disorders) plus neurological
complications
Neurological complications in
type 3 - lower/ gradual onset
than type 2 (National Gaucher
Foundation)
- Patients with type 3 survive
into adulthood or later life
(National Organisation for Rare
Diseases)

- Same symptoms as type 
1(hepatosplenomegaly, blood 
disorders) plus neurological 
complications

- Neurological complications in 
type 3 – lower/ gradual onset 
than type 2 (National Gaucher 
Foundation)

- Patients with type 3 survive 
into adulthood or later life 
(National Organisation for Rare 
Diseases)

disorders – horizontal 
gaze palsy (difficulty 
moving eyes side to

. . HEALTH CONSEQUENCES. Parkinson's Disease. Certain cancers. 

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Mutations of the GBA gene (encodes lysosomal enzyme glucocerebrosidase) can be found in Gaucher's disease – risk 
factor for Parkinson's disease (PD) (Riboldi GM, et al., 2019). The risk of PD is increased 6 to 17 times more in 
someone with Gaucher disease type 1 than the general population (Nguyen Y, et al., 2019).

The incidence of certain cancers such as hepatocellular carcinoma (liver cancer), melanoma and blood cancers-myeloma 
and lymphoma appear to be heightened in patients with Gaucher disease (Nguyen Y, et al., 2019). The accumulation of 
glucocerebroside – impacts immune system regulation (Choy FY, et al., 2011). Testing for Gaucher – allows for identification 
of these cancers (National Gaucher Foundation).

Patients with Gaucher disease can experience a loss of bone mineral content – impacts strength and structure of bones. 
This can lead to the onset of osteopenia or osteoporosis. The bones are more fragile and brittle – increases fracture risk. 
Gaucher disease treatment helps prevent development and identification of associated bone conditions (National Gaucher 
Foundation).

. . PREVALENCE. •Gaucher disease has a world-wide frequency of approximately 1 in 100,000 in the general population.. 

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•Gaucher disease has a world-wide frequency of 
approximately 1 in 100,000 in the general population.

•However, the prevalence of the disease is higher 
in Ashkenazi Jewish populations with 1 in 855 people 
having Gaucher disease. This is because this 
population presents higher for the mutation of the 
gene that codes for glucocerebrosidase.

•In Ireland, it is estimated that there are 11 patients 
with the disease, with a prevalence of 1 in 364,000.

. . DIAGNOSIS. . . A standardblood test is used to diagnose Gaucher disease. It is known as the beta-glucosidase leukocyte (BGL) test. It checks enzyme activity and identifies if the enzyme glucocerebrosidase is missing.. 

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A standardblood test is used to diagnose Gaucher disease. It is known 
as the beta-glucosidase leukocyte (BGL) test. It checks enzyme activity 
and identifies if the enzyme glucocerebrosidase is missing.

However, some carriers have border-line low enzyme activity so 
intense bone marrow testing is carried out in order to rule out 
leukaemia and other blood cancers.

If further tests are required, genetic analysis can confirm if a person 
has Gaucher disease. Gene sequencing can identify over 99% of the 
disease carriers.

For babies, the test is less invasive, and a heel prick is used to collect 
a blood sample.

. . NUTRITIONAL MANAGEMENT OF THE DISEASE. Normal liver Enlarged liver. 

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• Gaucher Disease leads to an overactive

recommended to prevent feeling of bloat / 
overeating

especially for vitamins and minerals such as 
Vitamin D and Calcium
(MAYO foundation for medical research and education)

. . NUTRITIONAL MANAGEMENT OF THE DISEASE. ◦ Calcium and vitamin D,. 

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are needed for strong 
bones especially for GD 
patients as reported 
by NIH Osteoporosis 
and Related Bone 
Diseases ~ National 
Resource Center)

. . POLICIES/ GUIDELINES. Policy for investigation of Gaucher Disease in symptomatic patients. 

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Policy for investigation of 
Gaucher Disease in 
symptomatic patients

Confirmation of Diagnosis 
by analysis of beat-
glucosidase activity

Identifying genetic 
mutations and biomarkers

Mandatory protocol for 
assessing the intensity of 
the deposit

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. . REFERENCES. Boer, Daphne E.C., Jeroen van Smeden, Joke A. Bouwstra, and Johannes M.F.G. Aerts 2020. "Glucocerebrosidase: Functions in and Beyond the Lysosome" Journal of Clinical Medicine 9, no. 3: 736. https://doi.org/10.3390/jcm9030736 (Accessed 2nd December 2021). 

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Boer, Daphne E.C., Jeroen van Smeden, Joke A. Bouwstra, and Johannes M.F.G. Aerts 2020. "Glucocerebrosidase: Functions in and Beyond the Lysosome" Journal of Clinical Medicine 9, no. 3: 736. 
https://doi.org/10.3390/jcm9030736 (Accessed 2nd December 2021)

Choy, F. Y., & Campbell, T. N. (2011). Gaucher disease and cancer: concept and controversy. International journal of cell biology, 2011, 150450. https://doi.org/10.1155/2011/150450

Gaucher Care (2021) “Testing for Gaucher Disease – Gaucher Care” (2021). Available at: <https://www.gauchercare.com/hcp/testing-for-gaucher-disease>

Gaucher disease. National Gaucher Foundation. Available at: https://www.gaucherdisease.org/about-gaucher-disease/symptoms/ (Accessed: 27th November 2021).

Gaucher disease. National Organisation for Rare Disorders. Available at: https://rarediseases.org/rare-diseases/gaucher-disease/ (Accessed: 27th November 2021).

Giraldo P; Grupo de Trabajo de las Guías de Actuación. Guía de actuación en pacientes con enfermedad de Gaucher tipo 1 [Guidelines for type 1 Gaucher's disease]. Med Clin (Barc). 2011 Sep;137 Suppl
1:55-60. Spanish. doi: 10.1016/S0025-7753(11)70019-7. PMID: 22230128.

Gupta, N., Oppenheim, I., Kauvar, E., Tayebi, N. and Sidransky, E., 2011. Type 2 Gaucher disease: Phenotypic variation and genotypic heterogeneity. Blood Cells, Molecules, and Diseases, 46(1), pp.75-84.

Irish Medical Times. (2021) “Gaucher's disease — diagnosis and therapy” Available at: <https://www.imt.ie/clinical/gauchers-disease-diagnosis-and-therapy-06-02-
2013/#:~:text=In%20Ireland%2C%20an%20estimated%2011,spleen%20(see%20Table%201)

Mayo Clinic (2020) ‘Gaucher Disease’ Available at Gaucher disease - Symptoms and causes - Mayo Clinic (Accessed 2nd December 2021)

MedlinePlus (2021) “Gaucher disease: MedlinePlus Genetics”. Medlineplus.gov. Available at: https://medlineplus.gov/genetics/condition/gaucher-disease/#frequency

Nagral, A. (2014). Gaucher Disease. Journal of Clinical and Experimental Hepatology, 4(1), 37–50. Available at doi:10.1016/j.jceh.2014.02.005. (Accessed 29th November 2021)

National Organisation of Rare Disorders (2018) ‘Gaucher Disease’ Available at Gaucher Disease - NORD (National Organization for Rare Disorders) (rarediseases.org). (Accessed 9th December 2021)

Nguyen, Y., Stirnemann, J. and Belmatoug, N., 2019. La maladie de Gaucher : quand y penser ?. La Revue de Médecine Interne, 40(5), pp.313-
322. https://www.sciencedirect.com/science/article/pii/S0248866318311858?via%3Dihub

Riboldi, G. M., & Di Fonzo, A. B. (2019). GBA, Gaucher Disease, and Parkinson's Disease: From Genetic to Clinic to New Therapeutic Approaches. Cells, 8(4), 364. https://doi.org/10.3390/cells8040364

Stirnemann, J., Belmatoug, N., Camou, F., Serratrice, C., Froissart, R., Caillaud, C., Levade, T., Astudillo, L., Serratrice, J., Brassier, A., Rose, C., Billette de Villemeur, T., & Berger, M. G. (2017). A Review of 
Gaucher Disease Pathophysiology, Clinical Presentation and Treatments. International journal of molecular sciences, 18(2), 441. https://doi.org/10.3390/ijms18020441

Gaucher Disease

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