MPS 1 H/S is also referred to as Hurler/Scheie syndrome. Hurler Scheie syndrome is an intermediate form of MPS 1H (Hurler syndrome).

What’s the Difference Between MPS 1 H and MPS 1 H/S?

The symptoms of Hurler Scheie syndrome manifests slower and later than the symptoms of Hurler syndrome. Variation in symptoms are dependent on each person. However, children diagnosed with Hurler Scheie syndrome are more likely to have an average life expectancy with intellectual disabilities appearing more gradually. 

MPS 1 S is also referred to as Scheie syndrome. Scheie syndrome is an attenuated form of MPS 1, characterized by milder manifestations of MPS 1 syndrome.

Diagnosis is most common in adolescence and usually stems from symptoms of joint contracture and hernias. Cognitive function is usually normal for this subtype and patients are expected to have an average life expectancy.

 

Hunter syndrome is a genetic disorder caused by a mutation in the IDS gene. The IDS gene is responsible for the degradation of the glycosaminoglycan sugar molecules. When glycosaminoglycans cannot be broken down, they accumulate in the cell, causing cellular malfunction leading to the symptoms we see in Hunter syndrome.

The IDS-gene is an X-chromosome gene. Chromosomes determine sex of the fetus. The X chromosome is passed down from the mother and the Y chromosome is passed from the father. That stated, Hunters syndrome is inherited from the mother who does not show symptoms, but carries the mutation. It is most commonly seen in males.

Hunter syndromes is placed in two categories: early and slowly progressive. The onset of symptoms and prognosis determine each category.

Hunter syndrome is seen in approximately 1 in every 100,000 to 170,000 births.

Symptoms of Hunter syndrome:

• Carpal tunnel
• Joint disease, resulting in stiffness
• Intellectual disability
• Deafness
• Recurrent ear infections
• Hernia
• Enlarged spleen and liver
• Cardiac disease
• Hip dysplasia

Physicalities:

• Large head
• Excessive hair growth
• Delayed growth
• Larger facial features
• Wide chest
• Short neck

Sanfilippo syndrome is an inherited genetic disorder caused by a mutation in the ability to catabolize heparan sulfate. Heparin sulfate is a polysaccharide (complex sugar molecule) responsible for cellular interaction. Without the proper enzyme to break down the sugar, heparin sulfate accumulates in the cell leading to a lysosomal storage condition. Because the lysosomes regulate the storage, degradation, and digestion of cellular waste, when glycosaminoglycans accumulate in the cell, it causes cellular malfunction leading to the symptoms we see in Sanfilippo syndrome.

There are four enzymes responsible for the catabolization of heparin sulfate. Each enzyme is associated with a different subtype of Sanfilippo syndrome, subtype A, B, C, and D.

1. Subtype A: Sulfamidase deficiency
   • Higher prevalence with most severe symptoms affect 1 in every 100,000 children. Symptoms have earlier onset and faster progression with inability to walk and talk within the first 2 years of life.
2. Subtype B: α–N-acetylhexosaminidase deficiency
   • Effecting approximately 1 in every 200,000 births. Symptoms appear later than Subtype A with less progression.
3. Subtype C: Acetyl-CoA:α-glucosamide N-acetyltransferase mutation
   • Least prevalent effecting approximately 1 in every 1.5 million children. Symptoms appear later with a variation in symptoms
4. Subtype D: N-acetylglucosamine-6-sulfate deficiency
   • Least prevalent effecting approximately 1 in every 1.5 million children. Symptoms appear later with a variation in symptoms

Symptoms of Sanfilippo syndrome:

• Intellectual disabilities
• Arthritis
• Deafness
• Enlarged liver and spleen
• Hernia
• Seizures
• Developmental regression
• Cornea clouding
• Sinus infections
• Ear infections
• Diarrhea
• Hyperactivity
• Sleep disturbances

Physicalities:

• Larger head
• Delayed growth
• Excessive hair growth

Morquio syndrome is an inherited disorder caused by the inability to break down keratan sulfate. Keratan sulfate is a polysaccharide (complex sugar) that controls cellular growth, cellular adhesion, and clot disruption. Without enough keratan sulfate, the sugar cannot perform its job and mucopolysaccharides flood into the lysosomes. Because the body does not produce enzymes for the degradation of lysosomal enzymes, mucopolysaccharides aggregate intracellularly and in connective tissues. The excessive amount of mucopolysaccharides causes cellular degradation leading to skeletal dysplasia.

There are two genes involved in cellular degradation of keratin sulfate. Each enzyme is associated with a different subtype of Morquio syndrome, subtype A and B.

1. Subtype A: N-acetyl galactosamine-6-sulfatase mutation
2. Subtype B: β-galactosidase mutation

Symptoms of Morquio syndrome:

• Scoliosis
• Kyphosis
• Enlarged liver and spleen
• Aortic regurgitation
• Hypermobile joints
• Cord compression
• Trouble hearing
• Heart disease
• Gluacoma

Physicalities:

• Delayed growth
• Larger chest
• Knock knees
• Spinal curve
• Broad mouth

Maroteaux-Lamy syndrome is an inherited disorder caused by the ARSB mutation. The ARSB gene is responsible for the production of the arylsufatase B enzyme that causes the degradation of glycosaminoglycans. When this gene is not present, glycosaminoglycans accumulate within lysosomes causing lysosomal storage conditions. Because the lysosomes regulate the storage, degradation, and digestion of cellular waste, the excessive accumulation causes vital organs and tissues to become inflamed and damaged. The continuous damage causes organ and tissue wasting that manifests as the symptoms seen in Margaux-Lamy syndrome.

Maroteaux-Lamy syndrome is an autosomal recessive gene, meaning it occurs when both parents carry the gene mutation. Maroteaux-Lamy syndrome is seen in approximately 1 in every 250,000 to 600,000 births.

Symptoms of Margaux-Lamy syndrome:

• Joint stiffness
• Heart disease
• Corneal clouding
• Deafness
• Breathing difficulty
• Enlarged liver and spleen
• Skeletal kyphosis and scoliosis

Physicalities:

• Round facial features
• Developmental delays
• Short stature

Sly syndrome is an inherited disorder caused by a mutation in the GUSB gene. The GUSB gene is responsible for production of beta-glucuronidase. Beta-glucoronidase is an enzyme responsible for the degradation of glycosaminoglycan sugars. When this gene is not present, glycosaminoglycans accumulate within lysosomes causing lysosomal storage conditions. Because the lysosomes regulate the storage, degradation, and digestion of cellular waste, the excessive accumulation causes vital organs and tissues to become inflamed and damaged. The continuous damage causes organ and tissue wasting that manifests as the symptoms seen in Sly syndrome.

Sly syndrome is an autosomal recessive gene, meaning it occurs when both parents carry the gene mutation. Sly syndrome is seen in approximately 1 in every 250,000 births.

Symptoms of Sly syndrome:

• Hypermobile joints
• Corneal cloudiness
• Enlarged liver and spleen
• Hernia
• Hearing loss
• Respiratory infections
• Heart murmurs
• Hydrocephalus
• Aortic regurgitation

Physicalities:

• Dwarfism
• Larger head
• Larger chest
• Short neck
• Flared ribs
• Club foot
• Macroglossia (enlarged tongue)
• *Scoliosis and kyphosis is rare
• Hirsutism

Natowicz syndrome is an inherited disorder caused a mutation in the HYAL1 gene. The HYAL1 gene is responsible for production of the hyaluronidase enzyme. Hyaraluronidase is critical in the break down hyaluronan, a glycosaminoglycan. When this gene is not present, glycosaminoglycans accumulate within the synovial fluid, skin, and cartilage manifesting as the symptoms of Natowicz syndrome.

Natowicz syndrome is the rarest form of MPS.

Symptoms of Natowicz syndrome:

• Joint pain and stiffness
• Cysts
• Gait
• Reduction in range of motion

Physicalities:

• Developmental delays
• Flattened nose
• Cleft palate