Mucopolysaccharidoses

• Lysosomal storage disorders (meaning enzyme deficiency leads to failure of breakdown of the offending agent: in this case, glycosaminoglycans).
• Thus, in all mucopolysaccharidoses, there is toxic accumulation of glycosaminoglycans (formerly called "mucopolysaccharides") that leads to organ damage.
• The glycosaminoglycans include > toxic accumulation of Heparan Sulphate, Dermatan Sulphate, Keratan Sulfate, Chondroitin Sulphate, Hyaluronan

• 7 Types (1, 2, 3, 4, 6, 7, 9) – Types 5 & 8 are now obsolete (Type 5 (Scheie) is now a mild subtype of Type 1, since the enzyme deficiency is the same and Type 8 was erroneous).

• Macrocephaly
• Dysostosis Multiplex – Skeletal abnormalities in MPS, which involve Short Stature and Joint Stiffness (limited mobility).
• Developmental Regression/Cognitive Delay
• Heart Valve Abnormalities
• Coarse Facial Features (formerly termed "Gargoylism")
• Hoarse Voice (due to enlarged vocal cords)
• Cataracts (Corneal Clouding)

• Range of Severity: Hurler is the most severe form of all of the mucopolysaccharidoses and results in toxic accumulation of heparin sulfate and dermatan sulfate. Scheie syndrome (formerly type 5, but now a mild variant of type 1) is the least severe of all of the mucopolysaccharidoses and results in toxic accumulation of dermatan sulfate, only.

• Type 1 – most severe ("Gargoylism")
• Type 2 – most aggressive, uniquely male (x-linked, recessive), NO corneal clouding, Ivory-white papules (pebbling)
• Type 3 – Least facial features, NO corneal clouding, Best Joint Mobility – can be misdiagnosed as Autism or ADHD.
• Type 4 – Good intellectual function/notable skeletal dysplasias (odontoid hypoplasia with cervical sublaxation and myleopathy) and joint hypermobility (instead of stiffness).
• Type 6 – Good intellectual function BUT classic features, otherwise, and prominent breast bone
• Type 7 – Possible hydrops fetalis

• All are Autosomal recessive, except Type 2, which is X-linked, recessive.

• Classic MPS symptoms/signs: (Hurler is the most severe form of all of the mucopolysaccharidoses vs the Scheie variant, which is the lease severe).

• IDUA gene mutation, Alpha-L-Iduronidase enzyme

• IDS gene mutation, Iduronate Sulfatase enzyme
• X-linked, recessive (so nearly exclusively Males)

• Multiple gene mutations with 4 different enzyme deficiencies

• 2 gene mutations with either N-Acetylgalactosamine-6-Sulfatase or Beta-Galactosidase deficiencies.

• ARSB gene (for arylsulfatase B enzyme)

• GSUB gene (for Beta-glucuronidase enzyme)

• Hyaluronidase enzyme

• Too few cases to be well established at present time.

• Calvo, Sherri; Collins, Heather; Greenberg, Kathleen, et. al at US National Library of Medicine, Genetics Home Reference. https://ghr.nlm.nih.gov