PPT on Mucopolysaccharidosis, introduction, clinical features and therapy

1. M U C O P O L Y S A C C H A R I D O S I S
H U M A N N U T R I T I O N
S u b m i t t e d B y V i o n a G u p t a , 2 1 8 6 2 9
S u b m i t t e d T o D r . D a n i e l l a C h y n e

2. INTRODUCTION
• Mucopolysaccharidosis refers to a group of inherited conditions in which the body is unable to properly breakdown
mucopolysaccharides.
• Seven distinct forms and numerous subtypes of mucopolysaccharidosis have been identified.
• All the MPS are autosomal recessive except Hunter Disease
• Mucopolysaccharidoses are a group of rare, inherited lysosomal storage disorders caused by a deficiency of a
lysosomal enzyme responsible for breaking down of glycosaminoglycans or GAGs

3. What Is A Mucopolysaccharide?
• Mucopolysaccharides are long chains of sugar molecules that are found throughout
the body, often in mucus and in fluid around the joints. They are more commonly called
glycosaminoglycans
• heteropolysaccharides composed of hexosamines and non-nitrogenous sugars linked
by glycosidic bonds
• The acidic glycosaminoglycans (mucopolysaccharides) form an important constituent of the
connective tissue and have the general role in supporting and binding together the cells
to form tissues, the tissues to form organs and the further organization of the organs into
the systems of the body.
• GAGs are degraded in the lysosome by the concerted action of a number of
exohydrolase activities following partial catabolism by
endoenzymes (endoglycosidases, hyaluronidases, heparanases, and endosulfatases)

4. General Clinical Features
M u c o p o l y s a c c h a r i d o s i s
Corneal Clouding
Skeletal Features
Coarse facial features and
Copious nasal discharge
Copious nasal discharge
And Short Stature
Clawing of Hands and
Protuberant Abdomen
• Umbilical Hernia
• Hepatosplenomegaly
• Dysostosis Multiplex
• Bullet Shaped middle phalanx
• Depressed Nasal Bridge
• Frontal bossing
• Growth Retardation

5. Skeletal Features

6. Specific Clinical Features
M u c o p o l y s a c c h a r i d o s i s
Mucopolysaccharides in Urine
Heparin Sulphate Dermitin Sulphate Reily Body Inclusions
In Leukocytes
• Mental Retardation • Atherosclerosis

7. Investment generally results in acquiring an
asset, also called an investment. If the asset is
available at a price worth investing, it is normally
expected either to generate income, or to
appreciate in value, so that it can be sold at a
higher price invest Investment generally results.
MPS SUBTYPES
Types Of MPS
Subdivisions of
Mucopolysaccharidoses
•MPS 1 H/S (Hurler/Scheie syndrome)
•MPS I H (Hurler disease)
•MPS II-(Hunter syndrome)
•MPS III A, B, C, and D (Sanfilippo syndrome)
•MPS I S (Scheie syndrome)
•MPS IV A and B (Morquio syndrome)
•MPS IX (hyaluronidase deficiency)
•MPS VII (Sly syndrome)

8. Investment generally results in acquiring an
asset, also called an investment. If the asset is
available at a price worth investing, it is normally
expected either to generate income, or to
appreciate in value, so that it can be sold at a
higher price invest Investment generally results.
MPS SUBTYPES
The GAGs that accumulate in each of the MPS disorders varies.
The table below highlights which GAGs are elevated in each of the MPS disorders.

9. Naglazyme
MPS Type VI
Elaprase
MPS Type II
Aldurazyme
MPS Type I
Enzyme Replacement Therapy

10. Y o u r G r e a t S u b t i t l e H e r e
Enzyme-Replacement Therapy in Mucopolysaccharidosis I
Abstract
BACKGROUND
Mucopolysaccharidosis I is a lysosomal storage disease caused by a deficiency of the enzyme α-L- iduronidase. We evaluated the effect of
enzyme-replacement therapy with recombinant human α-L- iduronidase in patients with this disorder.
METHODS
We treated 10 patients with mucopolysaccharidosis I (age, 5 to 22 years) with recombinant human α-L- iduronidase at a dose of 125,000 U per
kilogram of body weight given intravenously once weekly for 52 weeks. The patients were evaluated at base line and at 6, 12, 26, and 52
weeks by detailed clinical examinations, magnetic resonance imaging of the abdomen and brain, echocardiography, range-of-motion
measurements, polysomnography, clinical laboratory evaluations, measurements of leukocyte α-L-iduronidase activity, and urinary
glycosaminoglycan excretion.
RESULTS
Hepatosplenomegaly decreased significantly in all patients, and the size of the liver was normal for body weight and age in eight patients by 26
weeks. The rate of growth in height and weight had increased by a mean of 85 and 131 percent, respectively, at 52 weeks in the six prepubertal
patients. The mean maximal range of motion of shoulder flexion and elbow extension increased significantly. The number of episodes of apnea
and hypopnea during sleep decreased 61 percent. New York Heart Association functional class improved by one or two classes in all patients.
Urinary glycosaminoglycan excretion decreased after three to four weeks of treatment; the mean reduction at 52 weeks was 63 percent of
base-line values. Five patients had transient urticaria during infusions. Serum antibodies to α-L-iduronidase were detected in four patients.
CONCLUSIONS
In patients with mucopolysaccharidosis I, treatment with recombinant human α-L-iduronidase reduces lysosomal storage in the liver and
ameliorates some clinical manifestations of the disease.
Kakkis, E. D., Muenzer, J., Tiller, G. E., Waber, L., Belmont, J., Passage, M., ... & Neufeld, E. F. (2001). Enzyme-
replacement therapy in mucopolysaccharidosis I. New England Journal of Medicine, 344(3), 182-188.

11. References
• Kakkis, E. D., Muenzer, J., Tiller, G. E., Waber, L., Belmont, J., Passage, M., ... & Neufeld, E. F. (2001). Enzyme-replacement therapy in
mucopolysaccharidosis I. New England Journal of Medicine, 344(3), 182-188
• Paulina Mabe, Alf Valiente, Vivian Soto, Verónica Cornejo, Erna Raimann, Evaluation of reliability for urine mucopolysaccharidosis
screening by dimethylmethylene blue and Berry spot tests, Clinica Chimica Acta, Volume 345, Issues 1–2,2004
• References: 1. Muenzer J. Pediatrics. 2009;123(1):19-29. 2. Neufeld EF, Muenzer J. The Metabolic and Molecular Basis of
Inherited Disease. 2001:3421-3452. 3. Beck M. Genet Med. 2014;16(10):759-65.
• Khan SA, Peracha H, Ballhausen D, Wiesbauer A, Rohrbach M, Gautschi M, Mason RW, Giugliani R, Suzuki Y, Orii KE, Orii T,
Tomatsu S. Epidemiology of mucopolysaccharidoses.
• Mol Genet Metab. 2017; 121(3):227–240.
• Neufeld, E., & Muenzer, J. (2001). The Mucopolysaccharidoses. In C. Scriver, A. Beaudet & W. Sly (Eds.), The Metabolic and
Molecular Bases of Inherited Disease (pp. 3421-3452). New York, NY: McGraw Hill.
• Beck, M., Arn, P., Giugliani, R., Muenzer, J., Okuyama, T., Taylor, J., & Fallet, S. (2014). The natural history of MPS I: global
perspectives from the MPS I Registry. Genet Med.
• Terlato, N., & Cox, G. (2003). Can mucopolysaccharidosis type I disease severity be predicted based on a patient's genotype? A
comprehensive review of the literature. Genet Med, 5, 286-294.

12. Thank You