Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2014

Open Access 01-12-2014 | Research

Overcoming the barriers to diagnosis of Morquio A syndrome

Authors: Kaustuv Bhattacharya, Shanti Balasubramaniam, Yew Sing Choy, Michael Fietz, Antony Fu, Dong Kyu Jin, Ok-Hwa Kim, Motomichi Kosuga, Young Hee Kwun, Anita Inwood, Hsiang-Yu Lin, Jim McGill, Nancy J Mendelsohn, Torayuki Okuyama, Hasri Samion, Adeline Tan, Akemi Tanaka, Verasak Thamkunanon, Teck-Hock Toh, Albert D Yang, Shuan-Pei Lin

Published in: Orphanet Journal of Rare Diseases | Issue 1/2014

Login to get access

Abstract

Background

Morquio A syndrome is an autosomal recessive lysosomal storage disease often resulting in life-threatening complications. Early recognition and proficient diagnosis is imperative to facilitate prompt treatment and prevention of clinical complications.

Methods

Experts in Asia Pacific reviewed medical records focusing on presenting signs and symptoms leading to a diagnosis of Morquio A syndrome.

Results

Eighteen patients (77% female) had a mean (median; min, max) age of 77.1 (42.0; 0.0, 540.0) months at symptom onset, 78.9 (42.0; 4.5, 540.0) months at presentation and 113.8 (60.0; 7.0, 540.0) months at diagnosis. Orthopedic surgeons and pediatricians were most frequently consulted pre-diagnosis while clinical geneticists/metabolic specialists most frequently made the diagnosis. Delayed diagnoses were due to atypical symptoms for 5 patients (28%), while 4 patients (22%) experienced each of subtle symptoms, symptoms commonly associated with other diseases, or false-negative urine glycosaminoglycan analysis. Two patients (11%) each experienced overgrowth within the first year of life. Two patients with Morquio A syndrome (11%) were diagnosed with craniosynostosis and 1 (6%) for each of Legg-Calvé-Perthes disease, Leri-Weill syndrome, and pseudoachondroplasia. Early radiographic features of Morquio A syndrome led to more efficient diagnosis.

Conclusions

Increased awareness of clinical symptomology overlapping with Morquio A syndrome is essential. Clinicians encountering patients with certain skeletal dysplasia should consider Morquio A syndrome in their differential diagnosis. Atypical or subtle symptoms should not eliminate Morquio A syndrome from the differential diagnosis, especially for patients who may have non-classical phenotype of Morquio A syndrome.
Appendix
Available only for authorised users
Literature
1.
Di Ferrante N, Ginsberg LC, Donnelly PV, Di Ferrante DT, Caskey CT: Deficiencies of glucosamine-6-sulfate or galactosamine-6-sulfate sulfatases are responsible for different mucopolysaccharidoses. Science. 1978, 199: 79-81. 10.1126/science.199.4324.79.CrossRefPubMed
2.
Dorfman A, Arbogast B, Matalon R: The enzymatic defects in Morquio and Maroteaux-Lamy syndrome. Adv Exp Med Biol. 1976, 68: 261-276. 10.1007/978-1-4684-7735-1_18.CrossRefPubMed
3.
4.
5.
Hendriksz CJ, Lavery C, Coker M, Ucar SK, Jain M, Bell L, Lampe C: Burden of disease in patients with Morquio A syndrome: results from an international patient-reported outcomes survey. Orphanet J Rare Dis. 2014, 7 (9): 32-10.1186/1750-1172-9-32.CrossRef
6.
Spranger JW, Brill PW, Nishimura G, Superti-Furga A, Unger S: Section XIX: Lysosomal Storage Diseases With Skeletal Involvement (Dysostosis Multiplex). Bone Dysplasias. An Atlas of Genetic Disorders of Skeletal Development. 2012, Oxford University Press, Oxford, 565-629. 10.1093/med/9780195396089.003.0132.
7.
Montaño 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. 2007, 30: 165-174. 10.1007/s10545-007-0529-7.CrossRefPubMed
8.
Lin HY, Chuang CK, Chen MR, Chiu PC, Ke YY, Niu DM, Tsai FJ, Hwu WL, Lin JL, Lin SP: Natural history and clinical assessment of Taiwanese patients with mucopolysaccharidosis IVA. Orphanet J Rare Dis. 2014, 9 (Suppl 1): 21-10.1186/1750-1172-9-21.CrossRefPubMedPubMedCentral
9.
Hendriksz CJ, Harmatz P, Beck M, Jones S, Wood T, Lachman R, Gravance CG, Orii T, Tomatsu S: Review of clinical presentation and diagnosis of mucopolysaccharidosis IVA. Mol Genet Metab. 2013, 110 (Suppl 1–2): 54-64. 10.1016/j.ymgme.2013.04.002.CrossRefPubMedPubMedCentral
10.
Wood T, Harvey K, Beck M, Burin MG, Chien Y-H, Church HJ, D’Almeida V, van Diggelen OP, Fietz M, Giugliani R, Harmatz P, Hawley SM, Hwu WL, Ketteridge D, Lukacs Z, Miller N, Pasquali M, Schenone A, Thompson JN, Tylee K, Yu C, Hendriksz CJ: Diagnosing mucopolysaccharidosis IVA. J Inherit Metab Dis. 2013, 36 (Suppl 2): 293-307. 10.1007/s10545-013-9587-1.CrossRefPubMedPubMedCentral
11.
Hendriksz CJ, Al-Jawad M, Berger KI, Hawley SM, Lawrence R, Mc Ardle C, Summers CG, Wright E, Braunlin E: Clinical overview and treatment options for non-skeletal manifestations of mucopolysaccharidosis type IVA. J Inherit Metab Dis. 2013, 36 (Suppl 2): 309-322. 10.1007/s10545-012-9459-0.CrossRefPubMedPubMedCentral
12.
Northover H, Cowie RA, Wraith JE: Mucopolysaccharidosis type IVA (Morquio syndrome): a clinical review. J Inherit Metab Dis. 1996, 19: 357-365. 10.1007/BF01799267.CrossRefPubMed
13.
Harmatz P, Mengel KE, Giugliani R, Valayannopoulos V, Lin S-P, Parini R, Guffon N, Burton BK, Hendriksz CJ, Mitchell J, Martins A, Jones S, Guelbert N, Vellodi A, Hollak C, Slasor P, Decker C: The Morquio clinical assessment program: baseline results illustrating progressive, multisystemic clinical impairments in Morquio A subjects. Mol Genet Metab. 2013, 109 (Suppl 1): 54-61. 10.1016/j.ymgme.2013.01.021.CrossRefPubMed
14.
Solanki GA, Martin KW, Theroux MC, Lampe C, White KK, Shediac R, Lampe CG, Beck M, Mackenzie WG, Hendriksz CJ, Harmatz PR: Spinal involvement in mucopolysaccharidosis IVA (Morquio Brailsford or Morquio A syndrome): presentation, diagnosis and management. J Inherit Metab Dis. 2013, 36 (2): 339-355. 10.1007/s10545-013-9586-2.CrossRefPubMedPubMedCentral
15.
Morronea A, Tylee KL, Al-Sayed M, Brusius-Facchin AC, Caciotti A, Church HJ, Coll MJ, Davidson K, Fietz MJ, Gort L, Hegde M, Kubaski F, Lacerda L, Laranjeira F, Leistner-Segal S, Mooney S, Pajares S, Pollard L, Ribeiro I, Wang RY, Miller N: Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA) identifies 39 novel GALNS mutations. Mol Genet Metab. 2014, 112 (Suppl 2): 160-170. 10.1016/j.ymgme.2014.03.004.CrossRef
16.
Bunge S, Kleijer WJ, Tylki-Szymanska A, Steglich C, Beck M, Tomatsu S, Fukuda S, Poorthuis BJ, Czartoryska B, Orii T, Gal A: Identification of 31 novel mutations in the N-acetylgalactosamine-6-sulfatase gene reveals excessive allelic heterogeneity among patients with Morquio A syndrome. Hum Mutat. 1997, 10 (3): 223-232. 10.1002/(SICI)1098-1004(1997)10:3<223::AID-HUMU8>3.0.CO;2-J.CrossRefPubMed
17.
Tomatsu S, Fukuda S, Cooper A, Wraith JE, Ferreira P, Di Natale P, Tortora P, Fujimoto A, Kato Z, Yamada N, Isogai K, Yamagishi A, Sukegawa K, Suzuki Y, Shimozawa N, Kondo N, Sly WS, Orii T: Fourteen novel mucopolysaccharidosis IVA producing mutations in GALNS gene. Hum Mutat. 1997, 10 (5): 368-375. 10.1002/(SICI)1098-1004(1997)10:5<368::AID-HUMU6>3.0.CO;2-B.CrossRefPubMed
18.
Tomatsu S, Nishioka T, Montaño AM, Gutierrez MA, Pena OS, Orii KO, Sly WS, Yamaguchi S, Orii T, Paschke E, Kircher SG, Noguchi A: Mucopolysaccharidosis IVA: identification of mutations and methylation study in GALNS gene. J Med Genet. 2004, 41 (7): e98-10.1136/jmg.2003.018010.CrossRefPubMedPubMedCentral
19.
Tomatsu S, Fukuda S, Cooper A, Wraith JE, Rezvi GM, Yamagishi A, Yamada N, Kato Z, Isogai K, Sukegawa K, Kondo N, Suzuki Y, Shimozawa N, Orii T: Mucopolysaccharidosis IVA: identification of a common missense mutation I113F in the N-acetylgalactosamine-6-sulfate sulfatase gene. Am J Hum Genet. 1995, 57 (3): 556-563.PubMedPubMedCentral
20.
Ochiai T, Ito K, Okada T, Chin M, Shichino H, Mugishima H: Significance of extensive Mongolian spots in Hunter’s syndrome. Br J Dermatol. 2003, 148 (Suppl 6): 1173-1178. 10.1046/j.1365-2133.2003.05317.x.CrossRefPubMed
21.
Ochiai T, Suzuki Y, Kato T, Shichino H, Chin M, Mugishima H, Orii T: Natural history of extensive Mongolian spots in mucopolysaccharidosis type II (Hunter syndrome): a survey among 52 Japanese patients. J Eur Acad Dermatol Venereol. 2007, 21 (Suppl 8): 1082-1085. 10.1111/j.1468-3083.2007.02203.x.CrossRefPubMed
22.
23.
Mendelsohn NJ, Wood T, Olson RA, Temme R, Hale S, Zhang H, Read L, White KK: Spondyloepiphyseal dysplasias and bilateral legg-calvé-perthes disease: diagnostic considerations for mucopolysaccharidoses. JIMD Rep. 2013, 11: 125-132. 10.1007/8904_2013_231.CrossRefPubMedPubMedCentral
24.
Lachman RS, Burton BK, Clarke LA, Hoffinger S, Ikegawa S, Jin DK, Kano H, Kim OH, Lampe C, Mendelsohn NJ, Shediac R, Tanpaiboon P, White KK: Mucopolysaccharidosis IVA (Morquio A syndrome) and VI (Maroteaux-Lamy syndrome): under-recognized and challenging to diagnose. Skeletal Radiol. 2014, 43 (3): 359-369. 10.1007/s00256-013-1797-y.CrossRefPubMedPubMedCentral
25.
Hecht JT, Scott CI, Smith TK, Williams JC: Mild manifestations of the Morquio syndrome. Am J Med Genet. 1984, 18 (2): 369-371. 10.1002/ajmg.1320180222.CrossRefPubMed
26.
Aslam R, van Bommel AC, Hendriksz CJ, Jester A: Subjective and objective assessment of hand function in mucopolysaccharidosis IVa patients. JIMD Rep. 2013, 9: 59-65. 10.1007/8904_2012_179.CrossRefPubMedPubMedCentral
27.
Bank RA, Groener JE, van Gemund JJ, Maaswinkel PD, Hoeben KA, Schut HA, Everts V: Deficiency in N-acetylgalactosamine-6-sulfate sulfatase results in collagen perturbations in cartilage of Morquio syndrome A patients. Mol Genet Metab. 2009, 97 (Suppl 3): 196-201. 10.1016/j.ymgme.2009.03.008.CrossRefPubMed
28.
Yasuda E, Fushimi K, Suzuki Y, Shimizu K, Takami T, Zustin J, Patel P, Ruhnke K, Shimada T, Boyce B, Kokas T, Barone C, Theroux M, Mackenzie W, Nagel B, Ryerse JS, Orii KE, Iida H, Orii T, Tomatsu S: Pathogenesis of Morquio A syndrome: an autopsied case reveals systemic storage disorder. Mol Genet Metab. 2013, 109 (Suppl 3): 301-311. 10.1016/j.ymgme.2013.04.009.CrossRefPubMed
29.
Wessler E: Analytical and preparative separation of acidic glycosaminoglycans by electrophoresis in barium acetate. Anal Biochem. 1968, 26 (3): 439-444. 10.1016/0003-2697(68)90205-4.CrossRefPubMed
30.
Humbel R, Chamoles NA: Sequential thin layer chromatography of urinary acidic glycosaminglycans. Clin Chim Acta. 1972, 40 (1): 290-293. 10.1016/0009-8981(72)90287-2.CrossRefPubMed
31.
Tomatsu S, Okamura K, Maeda H, Taketani T, Castrillon SV, Gutierrez MA, Nishioka T, Fachel AA, Orii KO, Grubb JH, Cooper A, Thornley M, Wraith E, Barrera LA, Laybauer LS, Giugliani R, Schwartz IV, Frenking GS, Beck M, Kircher SG, Paschke E, Yamaguchi S, Ullrich K, Haskins M, Isogai K, Suzuki Y, Orii T, Kondo N, Creer M, Okuyama T, et al: Keratan sulfate levels in mucopolysaccharidoses and mucolipidoses. J Inher Metab Dis. 2005, 28 (Suppl 2): 187-202. 10.1007/s10545-005-5673-3.CrossRefPubMed
32.
Theroux MC, Nerker T, Ditro C, Mackenzie WG: Anesthetic care and perioperative complications of children with Morquio syndrome. Paediatr Anaesth. 2012, 22 (9): 901-907. 10.1111/j.1460-9592.2012.03904.x.CrossRefPubMed
Metadata
Title
Overcoming the barriers to diagnosis of Morquio A syndrome
Authors
Kaustuv Bhattacharya
Shanti Balasubramaniam
Yew Sing Choy
Michael Fietz
Antony Fu
Dong Kyu Jin
Ok-Hwa Kim
Motomichi Kosuga
Young Hee Kwun
Anita Inwood
Hsiang-Yu Lin
Jim McGill
Nancy J Mendelsohn
Torayuki Okuyama
Hasri Samion
Adeline Tan
Akemi Tanaka
Verasak Thamkunanon
Teck-Hock Toh
Albert D Yang
Shuan-Pei Lin
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2014
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-014-0192-7

Other articles of this Issue 1/2014

Orphanet Journal of Rare Diseases 1/2014 Go to the issue

Research

Unusual multisystemic involvement and a novel BAG3 mutation revealed by NGS screening in a large cohort of myofibrillar myopathies

Research

Holt Oram syndrome: a registry-based study in Europe

Research

The main pulmonary artery in adults: a controlled multicenter study with assessment of echocardiographic reference values, and the frequency of dilatation and aneurysm in Marfan syndrome

Research

Colchicine-free remission in familial Mediterranean fever: featuring a unique subset of the disease-a case control study

Research

The supposed tumor suppressor gene WWOX is mutated in an early lethal microcephaly syndrome with epilepsy, growth retardation and retinal degeneration

Research

Germline genes hypomethylation and expression define a molecular signature in peripheral blood of ICF patients: implications for diagnosis and etiology