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Genetics of Mucopolysaccharidosis Type IV Differential Diagnoses

  • Author: Nancy E Braverman, MS, MD; Chief Editor: Maria Descartes, MD  more...
Updated: Mar 24, 2014

Diagnostic Considerations

The differential diagnosis includes other mucopolysaccharidosis (MPS) disorders (see Table 1) and chondrodysplasias. The chondrodysplasias to consider are the spondyloepiphyseal dysplasias (SED) and the multiple epiphyseal dysplasias (MED).

Differential Diagnoses

Contributor Information and Disclosures

Nancy E Braverman, MS, MD Associate Professor, Department of Human Genetics, McGill University

Nancy E Braverman, MS, MD is a member of the following medical societies: Alpha Omega Alpha, Society for Inherited Metabolic Disorders, Society for the Study of Inborn Errors of Metabolism, American Society of Human Genetics

Disclosure: Nothing to disclose.


Julie Hoover-Fong, MD, PhD, FACMG Associate Professor, Director, Greenberg Center for Skeletal Dysplasias, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine

Julie Hoover-Fong, MD, PhD, FACMG is a member of the following medical societies: American College of Medical Genetics and Genomics, International Skeletal Dysplasia Society, American Society of Human Genetics

Disclosure: Nothing to disclose.

Michael C Ain, MD Associate Professor, Departments of Neurosurgery and General Surgery, Division of Pediatric Orthopaedic Surgery, Johns Hopkins University School of Medicine

Michael C Ain, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Orthopaedic Association, Scoliosis Research Society, Pediatric Orthopaedic Society of North America

Disclosure: Nothing to disclose.

Shunji Tomatsu, MD, PhD Professor, Department of Pediatrics, Saint Louis University School of Medicine

Shunji Tomatsu, MD, PhD is a member of the following medical societies: National MPS Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Margaret M McGovern, MD, PhD Professor and Chair of Pediatrics, Stony Brook University School of Medicine

Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

Karl S Roth, MD Retired Professor and Chair, Department of Pediatrics, Creighton University School of Medicine

Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

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Lateral view of spine in a child aged 8 years and 7 months. This radiograph shows advanced platyspondyly, irregularity, and anterior beaking of vertebral bodies characteristic of dysostosis multiplex. Note also the gibbus deformity and lordosis, which are characteristic of Morquio syndrome.
Cervical spine, flexion and extension views, in a child aged 5 years and 11 months. These flexion and extension images depict anterior and posterior subluxation, respectively, of the atlas secondary to odontoid hypoplasia.
Bilateral lower extremity views in a patient aged 22 years and 6 months. Metaphyseal irregularities and the characteristic genu valgus deformity are easily observed in this image.
Bilateral hand radiographs in a patient aged 22 years and 6 months. Note the tapering of the proximal portion of metacarpals 2 through 5 and small irregular carpal bones. The epiphyseal involvement characteristic of Morquio syndrome is exemplified by the tapered irregular distal radius and ulna. Overall, the bones are osteopenic with cortical thinning.
Upper extremities in a child aged 6 years and 11 months. Note the irregular epiphyses and widened metaphyses. Cortical thinning and mild widening of the diaphysis of the humerus are visible.
Multiple abnormalities are present in the pelvis, including dysplastic femoral heads and oblique acetabular roof with coxa valgus deformity. Flared iliac wings usually observed in Morquio syndrome are not well represented in this radiograph.
Anteroposterior view of the chest in a child aged 8 years and 4 months with Morquio syndrome. To reference the relatively small size of this chest, this patient's vital capacity was 500 cc, but the expected value based on height and weight was 1400 cc. Widened metaphyses and irregular epiphyses of the humeri and generalized platyspondyly are present. Oar-shaped ribs (widening ribs anteriorly and narrowing at the vertebrae) are easily observed and are another key characteristic of dysostosis multiplex.
Defects in keratan sulfate (KS) degradation resulting in Morquio syndrome.
The individual on the front of the scooter is 19 years old and has Morquio syndrome. Her friend on the back is an average-stature 10 year old without Morquio syndrome. On the driver, note the enlargement at the knees and the wrist deformity. Also, note the successful adaptation of the scooter to ambulate.
Note the short trunk and protuberant rib structure in this child with Morquio syndrome. More importantly, notice that Morquio syndrome is not preventing this child from being active and fishing.
Table 1. Clinical and Biochemical Features Distinguishing the Mucopolysaccharidoses and Morquio Syndrome (Mucopolysaccharidosis Type IV)
MPS TypeEponymDeficient


Neuro-degenerationSomatic Features*Corneal CloudingBone / Joint AbnormalityMucopoly-saccharide Stored
IHHurlerα -iduronidase++++++++++Dermatan sulfate (DS), heparan sulfate (HS)
IH/SHurler-Scheieα -iduronidase++++++DS, HS
ISScheieα -iduronidase+++DS, HS
IIHunterIduronidase sulfatase++++++DS, HS
III † Sanfilippo AHeparan sulfatase+++++HS
Sanfilippo BN -acetylgluco-saminidase+++++HS
Sanfilippo CAcetyl CoA glucosamine acetyltransferase+++++HS
Sanfilippo DN -acetylglucosamine-6-sulfatase+++++HS
IVMorquio AGalactosamine-6-sulfatase++ / —+ / ++ / +++KS, chondroitin sulfate (CS)
Morquio Bβ -galactosidase++ / —+ / ++ / +++KS, CS
VIMaroteaux-LamyN -acetylhexosamine-4-sulfatase++++DS
VIISly ‡ β -glucuronidase++++++DS, HS, CS
IXHyaluronidase deficiency § Hyaluronidase+Hyaluron
*Somatic features include organomegaly and facial coarsening.

† Eye findings may include cherry red spots.

‡ Severity widely varies; no neurologic degeneration is noted, but mental retardation is possible.

§ Only one patient has been described whose major features were periarticular soft tissue masses.

Table 2. Enzyme Replacement Therapy for the Mucopolysaccharidoses
MPS TypeDisease NameEnzyme DeficiencyERTCompanyClinical Use
IHurlerα -iduronidaselaronidase


GenzymeIn use
IH/SHurler-Scheieα -iduronidaselaronidaseGenzymeIn use
ISScheieα -iduronidaselaronidaseGenzymeIn use
IIHunterIduronidase sulfataseidursulfase


ShireIn use
III ‡ Sanfilippo AHeparan sulfatase.........
Sanfilippo BN- acetylglucosaminidase.........
Sanfilippo CAcetyl CoA glucosamine acetyltransferase.........
Sanfilippo DN -acetylglucosamine-6-sulfatase.........
IVMorquio AN-acetylgalactosamine-6-sulfataseelosulfase alfa (Vimizim)BioMarinIn use
Morquio Bβ -galactosidase.........
VIMaroteaux-LamyN -acetylhexosamine-4-sulfatasegalsulfase (Naglazyme)BioMarinIn use
VIISly § β -glucuronidase.........
IXHyaluronidase Deficiency || |Hyaluronidase.........
GSDIIPompeAcid α -glucosidasealglucosidase (Myozyme)GenzymeIn use
Note. This table represents the status of enzyme replacement therapy as of February 2014. Progress occurs on a daily basis; please investigate further for the most up to date information.
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