2. Lysosomal Storage Disorder
• Mucopolysaccharidoses are group of
inherited lysosomal storage disorders.
• Lysosomes function as primary
digestive units within cells.
• Enzymes within lysosomes break down or digest particular metabolites, such
as certain carbohydrates and fats.
• Deficiency or malfunction of specific lysosomes enzymes lead to abnormal
accumulation of certain complex carbohydrates known as
Mucopolysaccharides or Glycosaminoglycans.
3. Maroteaux Lamy Syndrome
• Arylsulfatase - B Deficiency
• MPS 6
• MPS type VI
• MPS VI
• Mucopolysaccharidosis type VI
• Polydystrophic dwarfism
4. Epidimiology
• Male and female are affected in equal
proportion.
• Occur 1:250000 – 600000 individuals
5. Introduction
• Inherited lysosomal storage disorder
• Rare genetic disorder
• Autosomal recessive
• Mutation in the ARSB gene (Arylsulfatase B gene)
• Partial/Complete lack of activity of the enzymes ARYLSULFATASE B
(N-ACETYLGALACTOSAMINE-4-SULFATASE)
6. • Mutation in the ARSB gene
• Which encodes the lysosomal enzyme Arylsulfatase B
• Deficiency of these enzymes lead to accumulation of dermatan sulfate and
chondritin sulfate in cells of various tissue
• As body cannot breakdown glycosaminoglycans.
• Lead to abnormal accumulation of complex carbohydrates(GAG) in various
organ – leading to multi-organ failure.
8. MLS
• Rapidly progressive MLS
– Onset of symptoms before age of 3 years
– Walking problem by age of 10 years
– Delayed or absence of puberty
– Risk of heart failure by second or third decades of life
• Slowly progressive MLS
– Later onset
– Diagnose usually after 5 year of age(2nd and 3rd decades)
9. Skeletal Abnormalities
• Dysostosis Multiplex (Group of skeletal deformities)
– Thickened , short bone of the palm and hands(Metacarpals)
– Underdevelope (Hypoplastic) and irregular carpal bones
– Abnormal tarsal bones
– Dysplastic femoral head and severe malformation of the hip
– Abnormalities of the ribs and spine
– Thickened clavicle
– Underdevelopment of bone of forearm
– Prominent breast bone (Pectus carinatum)
– Abnormal curvature of spine
– Knock-knees (Genu valgum)
– Carpal tunnel syndrome
– Tarsal tunnel syndrome
10. • Face and Neck
– Chubby faces
– Thickened lips (Gingival
hypertrophy)
– Frontal bossing
– Broad and flattened bridge
of nose
– Macroglossia
– Hirsutism
• Eye
– Clouding of cornea
• Vision loss
• Reduce peripheral vision
– Glaucoma (Increase IOP)
• Thinning, cupping or
notching of the disc rim
– Optic atrophy
• Heart
– Hypertension
– Valvular hear diseases
• AS,MS,AR,MR
– Heart failure
• Respiratory
– Obstructive airways diseases
– Breathlessness
– Recurrent pneumonia
– Tracheomalacia
• Nose and Ear
– Rhinorrhea
– Otitis media
• Conductive hearing
loss
– Damage to inner ear nerve
• Sensorinural
hearing loss
• Head
– Hydrocephalus
• Abdomen
– Hepatomegaly
– Splenomegaly
– Umbilical hernias
• Intelligence is usually not affected in
MLS.
• However learning difficulties are present
due to Visual and Hearing loss.
11. Diagnosis
• Elevated levels of GAG in urine (Mainly Dermatan
sulfate)
• Blood Sample – Measure activity of the enzymes
Arylsulfatase B
• Sequencing of ARSB gene should be performed
to identify the causative mutation.
12. Differential Diagnosis
• Scheie Syndrome (MPS-1)
– Deficiency of enzyme Alpha-L-Iduronidase
• Multiple Sulfatase Deficiency
– All seven sulfatase enzymes are not functional.
– All sulfatase enzyme deficiency will be present in blood sample.
– These patient may not learn to walk or speak.
13. Treatment
• Standeres Therapy
– Enzyme Replacement Therapy
• Naglazyme (Galsulfase) ERT which is genetically engineered (Recombinant) version.
• Investigational Therapies
– Hematopoetic Stem Cell Transplantation
– Pentosan poly-sulfate (PPS)
• Anti-inflamatory and pro-chondrogenic properties, lead to reduction in GAG in urine and
improvement in joint mobility and pain score. ( Under trails )
– Gene Therapy
