eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Metabolic Diseases
Mucopolysaccharidosis Type IV
Updated: Apr 21, 2009
Introduction
Background
Morquio syndrome (mucopolysaccharidosis type IV) is a member of a group of inherited metabolic disorders collectively termed mucopolysaccharidoses (MPSs). The MPSs are caused by a deficiency of lysosomal enzymes required for the degradation of mucopolysaccharides or glycosaminoglycans (GAGs). Eleven distinct single lysosomal enzyme deficiencies are known to cause 7 recognized phenotypes of MPS. All the MPSs are inherited in an autosomal recessive fashion except Hunter syndrome (MPS type II), which is X-linked.
In the early 1900s, Hunter and Hurler first described patients with MPS, whose diseases now bear their names; subsequent MPSs have been assigned numbers and eponyms loosely associated with the chronology and origin of their report.
In 1929, Morquio, a pediatrician in Uruguay, and Brailsford, a radiologist in England, simultaneously described cases of what is now believed to be Morquio syndrome. In the early 1930s, Husler coined the term dysostosis multiplex to describe the constellation of skeletal findings specific to patients with MPS and other lysosomal storage disorders. These included a large skull with a J-shaped sella, anterior hypoplasia of the thoracic and lumbar vertebral bodies, hypoplasia of the pelvis with small femoral heads and coxa valga, oar-shaped ribs (narrow at the vertebrae and widening anteriorly), diaphyseal and metaphyseal expansion of long bones with cortical thinning, and tapering of the proximal phalanges. However, this family of diseases was not described as the MPSs until 1952, when Brante isolated the stored mucopolysaccharides in these patients.
In 1957, Dorfman and Lorincz developed clinical assays to detect urinary mucopolysaccharides. The work of Neufeld et al from the late 1960s demonstrated that mucopolysaccharide accumulation in fibroblasts from patients with Hurler and Hunter syndromes could be corrected by co-culturing them with fibroblasts or tissue extracts from patients with a different MPS. This led to the purification and subsequent identification of each defective enzyme.
The MPSs share a chronic progressive course with multisystem involvement, several physical features, laboratory findings, and radiographic abnormalities; these include facial coarsening, hepatomegaly, excretion of urinary GAG fragments, and leukocyte inclusion bodies. Patients with Morquio syndrome (mucopolysaccharidosis type IV) can usually be clinically distinguished from patients with other MPSs because they do not have coarse facial features or mental retardation and they have additional skeletal manifestations derived from a unique spondyloepiphyseal dysplasia and ligamentous laxity. These skeletal manifestations include odontoid hypoplasia, a striking short trunk dwarfism, and genu valgus.
Compared with other patients who have MPS, those with Morquio syndrome (mucopolysaccharidosis type IV) tend to have greater spine involvement with scoliosis, kyphosis, and severe gibbus, as well as platyspondyly, rib flaring, pectus carinatum, and ligamentous laxity. Odontoid hypoplasia is the most critical skeletal feature to recognize in any patient with Morquio syndrome (mucopolysaccharidosis type IV).
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.
In 1976, the enzyme deficiency in Morquio syndrome type IVA (galactosamine-6-sulfatase deficiency [ie, N -acetyl-galactosamine-6-sulfate sulfatase deficiency]) was identified. Shortly thereafter, the enzyme deficiency in Morquio syndrome type IVB was described (β -galactosidase deficiency). Historically, type IVA was considered to have more severe manifestations than type IVB. However, with the ability to differentiate between types A and B by enzyme analysis, variability in clinical expression within both groups is apparent. No clear clinical differentiation between Morquio syndrome type IVA and IVB is recognized.
More recently, Montano et al collected natural histories on 354 patients with Morquio syndrome type IVA by questionnaire.1 In addition, Morquio syndrome type IVA specific growth curves were generated.
Pathophysiology
GAGs are oligosaccharide components of proteoglycans (macromolecules that provide structural integrity and function to connective tissues). The underlying defect in the MPSs is inability to degrade GAGs. The chronic progressive course is caused by the accumulation of partially degraded GAG, with resulting thickening of tissue and compromising of cell and organ function over time. Some of the clinical manifestations of GAG accumulation are coarse facial features, corneal clouding, thickened skin, and organomegaly. Some of the manifestations of abnormal cell function are mental retardation, growth failure, and skeletal dysplasia. GAGs accumulate in lysosomes and extracellular tissue and are excreted in the urine.Dermatan sulfate, heparan sulfate, keratan sulfate (KS), and chondroitin sulfate are the main GAGs in tissues. They are composed of sulfated sugar and uronic acid residues (except for KS, which is mainly composed of galactose 6-sulfate alternating with sulfated N -acetylglucosamine residues) and are degraded in a stepwise fashion from the nonreducing end by a series of lysosomal enzymes. Depending on the specific enzyme deficiency, the catabolism of one or more GAGs may be blocked. Clinical features vary depending on the tissue distribution of the affected substrate and the degree of enzyme deficiency.
In Morquio syndrome (mucopolysaccharidosis type IV), the degradation of KS is defective because of deficiency of either N -acetyl-galactosamine-6-sulfate sulfatase (GALNS gene) in Morquio syndrome type IVA or β -galactosidase (GLB1 gene) in Morquio syndrome type IVB (see Media file 8). Defective GALNS also affects the catabolism of chondroitin 6-sulfate.
Defects in keratan sulfate (KS) degradation resulting in Morquio syndrome.
KS is predominantly found in cartilage and cornea, the major organs affected in Morquio syndrome (mucopolysaccharidosis type IV). Heparan and dermatan sulfate have a more generalized tissue distribution. Their normal metabolism in patients with Morquio syndrome (mucopolysaccharidosis type IV) spares these patients from mental retardation and disease manifestations observed in other types of MPS.
The specific mechanism or mechanisms by which excess storage of KS results in the skeletal dysplasia unique to Morquio syndrome remains unknown. The biology of KS is currently under investigation. Numerous KS-containing proteins have been identified, and the elucidation of their functional roles will provide a better understanding of the pathophysiology of Morquio syndrome (mucopolysaccharidosis type IV). A few histological reports in patients are noted.
Three murine models for GALNS deficiency were recently generated and consist of a traditional null model and a more complex model engineered to achieve tolerance when challenged by the human enzyme in therapeutic applications. The latter expresses both the human and mouse GALNS proteins, containing an inactivating missense mutation in the highly conserved cysteine residue within the catalytic domain. The third expresses only the murine missense GALNS. These models accumulate GAGs in multiple tissues, including bone, and will be useful for study. Additional data on these mouse models, presented by Tomatsu et al, reveal that their skeletal phenotype is limited by expression of only KS type I, in contrast to humans who express KS types 1 and 2.2
The GALNS gene is located on chromosome arm 16q24.3 and encodes a 522–amino acid protein that is stabilized in a complex with 2 other lysosomal enzymes (β -galactosidase and α -neuraminidase) and the protective protein cathepsin A. The assembly of these 4 components is necessary for correct posttranslation processing and stability of the component enzymes and for the efficient catabolism of KS. More than 148 unique mutations have been reported in the GALNS gene. A few of these mutations represent founder alleles in certain population groups. Missense alleles represent the most prevalent type of mutations. Milder phenotypes may be explained, in part, by the residual activity of the mutant proteins.
The GLB1 gene is located on chromosome arm 3p21.33 and encodes a 677 catalytically active protein. A minor alternative transcript encodes S-GAL, an elastin-binding protein required for the orderly assembly of elastin and other cell-matrix interactions. β -galactosidase deficiency also causes GM1 gangliosidosis, a neurodegenerative disorder with minimal resemblance to Morquio syndrome (mucopolysaccharidosis type IV). The mutations that cause Morquio syndrome (mucopolysaccharidosis type IV) are proposed to affect the catabolism of KS but have little effect on GM1 gangliosides. Deficiency of cathepsin A also results in a secondary deficiency of GLB1; this disorder is galactosialidosis.
Frequency
United States
Incidence is unknown at present, but estimates may be available soon following the institution of newborn screening for lysosomal storage disorders. Development of newborn screening strategies is underway.
International
The estimated incidence of Morquio syndrome (mucopolysaccharidosis type IV) covers a wide range, including 1 case per 75,000 births in Northern Ireland, 1 case per 200,000 births in British Columbia, and 1 case per 263,157 births in Germany. One study also identified the first GALNS mutations in Tunisia in 6 affected individuals from 4 unrelated families.
Mortality/Morbidity
In Morquio syndrome (mucopolysaccharidosis type IV), mortality and morbidity rates are primarily related to the atlantoaxial instability and subsequent cervical myelopathy. A minor fall or extension of the neck can result in cord transection and subsequent quadriparesis or death. The cervical myelopathy can cause bowel and bladder dysfunction and apnea. Obstructive sleep apnea can cause prolonged periods of hypoxia, pulmonary hypertension, and even death. Airway obstruction also occurs secondary to thickening of tissue in the upper airway from mucopolysaccharide deposition.
Patients with Morquio syndrome (mucopolysaccharidosis type IV) have a predisposition to pulmonary infection because of progressive truncal deformity and immobility. Early onset coronary heart disease and valve thickening (aortic and mitral) with resultant cardiac dysfunction are described in these patients, and endocarditis prophylaxis is recommended. Corneal clouding can cause visual disturbance and photophobia. Enamel abnormalities in patients with Morquio syndrome (mucopolysaccharidosis type IV) predispose them to dental caries.
Based on a natural history study, patients with more severe short stature and those who underwent surgical procedures were reported to have more difficulties ambulating. The current clinical criteria establish that reduced growth and final height are associated with more severe clinical phenotypes. Increased relative weight in this population was also associated with increased morbidity.3
Race
No racial predilection is noted.
Sex
The male-to-female ratio is 1:1, and this is supported by the demographics of the cohort in a natural history study.1
Age
Patients with Morquio syndrome (mucopolysaccharidosis type IV) appear healthy at birth. The mean age of onset of the disease is 2.1 years, and 76% of children are diagnosed by age 6 years. Children are often evaluated for the first time for spinal deformity, growth retardation, and genu valgus in the second or third year of life. Morquio-specific radiographic changes occurring before phenotypic changes are obvious have been reported. Patients with mild manifestations of Morquio syndrome (mucopolysaccharidosis type IV), regardless of type, have been reported to survive into the seventh decade of life. Patients with severe manifestations, primarily related to cervical instability, do not survive this long.
Clinical
History
The patient with Morquio syndrome (mucopolysaccharidosis type IV) is usually evaluated during the second or third year of life for unusual skeletal features. These include short trunk dwarfism, pectus carinatum, kyphosis, gibbus, scoliosis, genu valgus, flaring of the lower ribs, and joint abnormalities (joints range from hypermobile to contracted).
- At the time of initial evaluation, families commonly report a history of increased clumsiness and falling.
- Because no mental deficiencies or loss of developmental milestones occurs, this is not a presenting symptom. In fact, this is one important characteristic that distinguishes Morquio syndrome (mucopolysaccharidosis type IV) from many of the other mucopolysaccharidoses (MPSs).
- Because the MPSs are progressive disorders, the patient becomes more severely affected over time. As lysosomal accumulation of keratan sulfate (KS) continues, mild coarsening of facial features, corneal clouding, and hepatomegaly become apparent.
- Other less frequent findings in Morquio syndrome (mucopolysaccharidosis type IV) include hearing difficulties, hernias, and thin tooth enamel with a predisposition to caries.
- A characteristic of all patients with Morquio syndrome (mucopolysaccharidosis type IV) is odontoid hypoplasia. In combination with ligamentous laxity and extradural mucopolysaccharide deposition, this results in atlantoaxial subluxation, with consequential quadriparesis or even death.
- A history of exercise intolerance in patients with Morquio syndrome often predicts the presence of occult cervical myelopathy, which can also cause bowel and bladder dysfunction.
Physical
- The most dramatic finding in patients with Morquio syndrome is their skeletal habitus. This includes short stature with short trunk, pectus carinatum, kyphosis, gibbus, scoliosis, genu valgus, flaring of the lower ribs, and joint abnormalities (joints range from hypermobile to contracted). Patients can alternatively have genu varus.
- Additional physical features are hearing difficulties, carious teeth, hepatomegaly, and aortic and/or mitral regurgitation.[#Table]
Table 1.Clinical and Biochemical Features Distinguishing the Mucopolysaccharidoses and Morquio Syndrome (Mucopolysaccharidosis Type IV)
Open table in new window
Table
| MPS Type | Eponym | Deficient Enzyme | Neurodegeneration | Somatic Features* | Corneal Clouding | Bone/Joint Abnormality | Mucopolysaccharide Stored |
| IH | Hurler | α-iduronidase | +++ | +++ | ++ | ++ | Dermatan sulfate (DS), heparan sulfate (HS) |
| IH/S | Hurler-Scheie | α-iduronidase | — | ++ | ++ | ++ | DS, HS |
| IS | Scheie | α-iduronidase | — | + | + | + | DS, HS |
| II | Hunter | Iduronidase sulfatase | ++ | ++ | — | ++ | DS, HS |
| III† | Sanfilippo A | Heparan sulfatase | +++ | + | — | + | HS |
| Sanfilippo B | N -acetylglucosaminidase | +++ | + | — | + | HS | |
| Sanfilippo C | Acetyl CoA glucosamine acetyltransferase | +++ | + | — | + | HS | |
| Sanfilippo D | N -acetylglucosamine-6-sulfatase | +++ | + | — | + | HS | |
| IV | Morquio A | Galactosamine-6-sulfatase | — | + | + / — | + / ++ / +++ | KS, chondroitin sulfate (CS) |
| Morquio B | β-galactosidase | — | + | + / — | + / ++ / +++ | KS, CS | |
| V | Nonexistent | ||||||
| VI | Maroteaux-Lamy | N -acetylhexosamine-4-sulfatase | — | + | + | ++ | DS |
| VII | Sly‡ | β-glucuronidase | — | ++ | ++ | ++ | DS, HS, CS |
| IX | Hyaluronidase deficiency§ | Hyaluronidase | — | — | — | + | Hyaluron |
| MPS Type | Eponym | Deficient Enzyme | Neurodegeneration | Somatic Features* | Corneal Clouding | Bone/Joint Abnormality | Mucopolysaccharide Stored |
| IH | Hurler | α-iduronidase | +++ | +++ | ++ | ++ | Dermatan sulfate (DS), heparan sulfate (HS) |
| IH/S | Hurler-Scheie | α-iduronidase | — | ++ | ++ | ++ | DS, HS |
| IS | Scheie | α-iduronidase | — | + | + | + | DS, HS |
| II | Hunter | Iduronidase sulfatase | ++ | ++ | — | ++ | DS, HS |
| III† | Sanfilippo A | Heparan sulfatase | +++ | + | — | + | HS |
| Sanfilippo B | N -acetylglucosaminidase | +++ | + | — | + | HS | |
| Sanfilippo C | Acetyl CoA glucosamine acetyltransferase | +++ | + | — | + | HS | |
| Sanfilippo D | N -acetylglucosamine-6-sulfatase | +++ | + | — | + | HS | |
| IV | Morquio A | Galactosamine-6-sulfatase | — | + | + / — | + / ++ / +++ | KS, chondroitin sulfate (CS) |
| Morquio B | β-galactosidase | — | + | + / — | + / ++ / +++ | KS, CS | |
| V | Nonexistent | ||||||
| VI | Maroteaux-Lamy | N -acetylhexosamine-4-sulfatase | — | + | + | ++ | DS |
| VII | Sly‡ | β-glucuronidase | — | ++ | ++ | ++ | DS, HS, CS |
| IX | Hyaluronidase deficiency§ | Hyaluronidase | — | — | — | + | Hyaluron |
†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.
Causes
Excess deposition of KS underlies the clinical manifestations of this disease (see Pathophysiology).
More on Mucopolysaccharidosis Type IV |
 Overview: Mucopolysaccharidosis Type IV |
| Differential Diagnoses & Workup: Mucopolysaccharidosis Type IV |
| Treatment & Medication: Mucopolysaccharidosis Type IV |
| Follow-up: Mucopolysaccharidosis Type IV |
| Multimedia: Mucopolysaccharidosis Type IV |
| References |
| Next Page » |
References
Montano AM, Tomatsu S, Gottesman GS, Smith M, Orii T. International Morquio A Registry: clinical manifestation and natural course of Morquio A disease. J Inherit Metab Dis. Apr 2007;30(2):165-74. [Medline].
Tomatsu S, Montano AM, Ohashi A, et al. Enzyme replacement therapy in a murine model of Morquio A syndrome. Hum Mol Genet. Mar 15 2008;17(6):815-24. [Medline].
Montano AM, Tomatsu S, Brusius A, Smith M, Orii T. Growth charts for patients affected with Morquio A disease. Am J Med Genet A. May 15 2008;146A(10):1286-95. [Medline].
Ain MC, Chaichana KL, Schkrohowsky JG. Retrospective study of cervical arthrodesis in patients with various types of skeletal dysplasia. Spine. Mar 15 2006;31(6):E169-74. [Medline].
Tobias JD. Anesthetic care for the child with Morquio syndrome: general versus regional anesthesia. J Clin Anesth. May 1999;11(3):242-6. [Medline].
Institute for Clinical Systems Improvement (ICSI). Immunizations. Bloomington, MN: Institute for Clinical Systems Improvement (ICSI); 2008.
Cunningham M, Cox EO. Hearing assessment in infants and children: recommendations beyond neonatal screening. Pediatrics. Feb 2003;111(2):436-40. [Medline].
Ashworth JL, Biswas S, Wraith E, Lloyd IC. Mucopolysaccharidoses and the eye. Surv Ophthalmol. Jan-Feb 2006;51(1):1-17. [Medline].
Baehner F, Schmiedeskamp C, Krummenauer F, et al. Cumulative incidence rates of the mucopolysaccharidoses in Germany. J Inherit Metab Dis. 2005;28(6):1011-7. [Medline].
Callahan JW. Molecular basis of GM1 gangliosidosis and Morquio disease, type B. Structure-function studies of lysosomal beta-galactosidase and the non-lysosomal beta-galactosidase-like protein. Biochim Biophys Acta. Oct 8 1999;1455(2-3):85-103. [Medline].
Defraia E, Marinelli A, Antonini A, Giuntini V. Abnormal mandibular growth after craniovertebral surgery in Morquio syndrome type A. Angle Orthod. May 2005;75(3):461-4. [Medline].
Factor SM, Biempica L, Goldfischer S. Coronary intimal sclerosis in Morquio's syndrome. Virchows Arch A Pathol Anat Histol. Aug 4 1978;379(1):1-10. [Medline].
Funderburgh JL. Keratan sulfate: structure, biosynthesis, and function. Glycobiology. Oct 2000;10(10):951-8. [Medline].
Hinek A, Zhang S, Smith AC, Callahan JW. Impaired elastic-fiber assembly by fibroblasts from patients with either Morquio B disease or infantile GM1-gangliosidosis is linked to deficiency in the 67-kD spliced variant of beta-galactosidase. Am J Hum Genet. Jul 2000;67(1):23-36. [Medline]. [Full Text].
Hoffmann B, Mayatepek E. Neurological manifestations in lysosomal storage disorders - from pathology to first therapeutic possibilities. Neuropediatrics. Oct 2005;36(5):285-9. [Medline].
Holzgreve W, Grobe H, von Figura K, et al. Morquio syndrome: clinical findings in 11 patients with MPS IVA and 2 patients with MPS IVB. Hum Genet. 1981;57(4):360-5. [Medline].
Hoogerbrugge PM, Brouwer OF, Bordigoni P, et al. Allogeneic bone marrow transplantation for lysosomal storage diseases. The European Group for Bone Marrow Transplantation. Lancet. Jun 3 1995;345(8962):1398-402. [Medline].
Hopwood JJ, Morris CP. The mucopolysaccharidoses. Diagnosis, molecular genetics and treatment. Mol Biol Med. Oct 1990;7(5):381-404. [Medline].
Laradi S, Tukel T, Khediri S, et al. Mucopolysaccharidosis type IV: N-acetylgalactosamine-6-sulfatase mutations in Tunisian patients. Mol Genet Metab. Mar 2006;87(3):213-8. [Medline].
Leslie T, Siddiqui MA, Aitken DA, et al. Morquio syndrome: electron microscopic findings. Br J Ophthalmol. Jul 2005;89(7):925-6. [Medline].
McKusick VA. The nosology of the mucopolysaccharidoses. Am J Med. Nov 1969;47(5):730-47. [Medline].
Meikle PJ, Ranieri E, Simonsen H, et al. Newborn screening for lysosomal storage disorders: clinical evaluation of a two-tier strategy. Pediatrics. Oct 2004;114(4):909-16. [Medline]. [Full Text].
Millington DS. Newborn screening for lysosomal storage disorders. Clin Chem. May 2005;51(5):808-9. [Medline]. [Full Text].
Natowicz MR, Short MP, Wang Y, et al. Clinical and biochemical manifestations of hyaluronidase deficiency. N Engl J Med. Oct 3 1996;335(14):1029-33. [Medline].
Nelson J. Incidence of the mucopolysaccharidoses in Northern Ireland. Hum Genet. Dec 1997;101(3):355-8. [Medline].
Neufeld EF. Lysosomal storage diseases. Annu Rev Biochem. 1991;60:257-80. [Medline].
Neufeld EF, Muenzer J. The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS, eds. The Metabolic and Molecular Bases of Inherited Disease. 2001. 8th ed. New York, NY: McGraw-Hill, Inc; 3421-52.
Northover H, Cowie RA, Wraith JE. Mucopolysaccharidosis type IVA (Morquio syndrome): a clinical review. J Inherit Metab Dis. 1996;19(3):357-65. [Medline].
Resnick D. Osteochondrodysplasias, dysostoses, chromosomal aberrations, mucopolysaccharidoses, mucolipidoses and other skeletal dysplasias. In: Diagnosis of Bone and Joint Disorders V-5. Philadelphia, PA: WB Saunders Co; 1988:3501-7.
Rigante D, Antuzzi D, Ricci R, Segni G. Cervical myelopathy in mucopolysaccharidosis type IV. Clin Neuropathol. Mar-Apr 1999;18(2):84-6. [Medline].
Shinhar SY, Zablocki H, Madgy DN. Airway management in mucopolysaccharide storage disorders. Arch Otolaryngol Head Neck Surg. Feb 2004;130(2):233-7. [Medline].
Sukegawa K, Nakamura H, Kato Z, et al. Biochemical and structural analysis of missense mutations in N- acetylgalactosamine-6-sulfate sulfatase causing mucopolysaccharidosis IVA phenotypes. Hum Mol Genet. May 22 2000;9(9):1283-90. [Medline]. [Full Text].
Suzuki Y, Oshima A, Nanba E. Beta-galactosidase deficiency (beta-gGalactosidosis): GM1 gangliosidosis and Morquio B disease. In: Scriver CR, Beaudet AL, Sly WS, eds. The Metabolic and Molecular Basis of Inherieted Disease. 8th ed. Philadelphia, PA: McGraw-Hill, Inc; 2001:3775-809.
Tomatsu S, Gutierrez M, Nishioka T, et al. Development of MPS IVA mouse (Galnstm(hC79S.mC76S)slu) tolerant to human N-acetylgalactosamine-6-sulfate sulfatase. Hum Mol Genet. Nov 15 2005;14(22):3321-35. [Medline].
Tomatsu S, Montano AM, Nishioka T, et al. Mutation and polymorphism spectrum of the GALNS gene in mucopolysaccharidosis IVA (Morquio A). Hum Mutat. Dec 2005;26(6):500-12. [Medline].
Tomatsu S, Okamura K, Taketani T, et al. Development and testing of new screening method for keratan sulfate in mucopolysaccharidosis IVA. Pediatr Res. Apr 2004;55(4):592-7. [Medline]. [Full Text].
Tomatsu S, Orii KO, Vogler C, et al. Mouse model of N-acetylgalactosamine-6-sulfate sulfatase deficiency (Galns-/-) produced by targeted disruption of the gene defective in Morquio A disease. Hum Mol Genet. Dec 15 2003;12(24):3349-58. [Medline].
Tomatsu S, Vogler C, Montano AM, et al. Murine model (Galns(tm(C76S)slu)) of MPS IVA with missense mutation at the active site cysteine conserved among sulfatase proteins. Mol Genet Metab. Jul 2007;91(3):251-8. [Medline].
Ullrich K. Screening for lysosomal disorders. Eur J Pediatr. 1994;153(7 Suppl 1):S38-43. [Medline].
Urban Z, Boyd CD. Elastic-fiber pathologies: primary defects in assembly and secondary disorders in transport and delivery. Am J Hum Genet. Jul 2000;67(1):4-7. [Medline].
Yuen M, Fensom AH. Diagnosis of classical Morquio's disease: N-acetylgalactosamine 6-sulphate sulphatase activity in cultured fibroblasts, leukocytes, amniotic cells and chorionic villi. J Inherit Metab Dis. 1985;8(2):80-6. [Medline].
Further Reading
Keywords
mucopolysaccharidosis type IV, Morquio syndrome, MS, mucopolysaccharidosis type IVA, OMIM 253000, mucopolysaccharidosis type IVB, OMIM 253010, lysosomal storage disease, MPS IVA, MPS IVB, dysostosis multiplex, lysosomal storage disorders, facial coarsening, hepatomegaly, platyspondyly, rib flaring, pectus carinatum, mental retardation, growth failure, skeletal dysplasia, obstructive sleep apnea, short trunk dwarfism, pectus carinatum, kyphosis, gibbus, scoliosis, genu valgus, flaring of the lower ribs, exercise intolerance, treatment, diagnosis
