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Overcoming the barriers to diagnosis of Morquio A syndrome.

Bhattacharya K, Balasubramaniam S, Choy YS, Fietz M, Fu A, Jin DK, Kim OH, Kosuga M, Kwun YH, Inwood A, Lin HY, McGill J, Mendelsohn NJ, Okuyama T, Samion H, Tan A, Tanaka A, Thamkunanon V, Toh TH, Yang AD, Lin SP - Orphanet J Rare Dis (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Genetic Metabolic Disorders Service, The Children's Hospital at Westmead, Hawkesbury Rd & Hainsworth St, Westmead, Sydney, NSW, Australia. kaustuv.bhattacharya@health.nsw.gov.au.

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.

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Related in: MedlinePlus

Growth charts for a Japanese patient (a) and an Australian patient (b) diagnosed with Morquio A syndrome despite experiencing overgrowth in their early years.
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Fig1: Growth charts for a Japanese patient (a) and an Australian patient (b) diagnosed with Morquio A syndrome despite experiencing overgrowth in their early years.

Mentions: Complete information about pre-diagnostic referrals was not available, although patients were commonly referred to pediatricians, geneticists, and orthopedic surgeons. Clinical geneticists/metabolic specialists most frequently made the diagnosis of Morquio A (Table 1). Patients presented with a wide variety and spectrum of symptoms (Table 1). Symptoms not commonly associated with Morquio A that occurred in 2 (11%) patients in this cohort were overgrowth in the first year of age and extensive dermal melanocytosis (colloquially referred to as Mongolian blue spots) (Table 1). Both patients with overgrowth were diagnosed in their early years (Figure 1) including 1 patient from Australia diagnosed at 12 months based on radiographic evidence and elevated uGAG levels despite being >95th percentile for length, weight and head circumference. Another patient from Japan, also classified as experiencing overgrowth within the first year of life, was diagnosed at 3.3 years with the clinical suspicion based on other physical features associated with Morquio A.Figure 1


Overcoming the barriers to diagnosis of Morquio A syndrome.

Bhattacharya K, Balasubramaniam S, Choy YS, Fietz M, Fu A, Jin DK, Kim OH, Kosuga M, Kwun YH, Inwood A, Lin HY, McGill J, Mendelsohn NJ, Okuyama T, Samion H, Tan A, Tanaka A, Thamkunanon V, Toh TH, Yang AD, Lin SP - Orphanet J Rare Dis (2014)

Growth charts for a Japanese patient (a) and an Australian patient (b) diagnosed with Morquio A syndrome despite experiencing overgrowth in their early years.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4279997&req=5

Fig1: Growth charts for a Japanese patient (a) and an Australian patient (b) diagnosed with Morquio A syndrome despite experiencing overgrowth in their early years.
Mentions: Complete information about pre-diagnostic referrals was not available, although patients were commonly referred to pediatricians, geneticists, and orthopedic surgeons. Clinical geneticists/metabolic specialists most frequently made the diagnosis of Morquio A (Table 1). Patients presented with a wide variety and spectrum of symptoms (Table 1). Symptoms not commonly associated with Morquio A that occurred in 2 (11%) patients in this cohort were overgrowth in the first year of age and extensive dermal melanocytosis (colloquially referred to as Mongolian blue spots) (Table 1). Both patients with overgrowth were diagnosed in their early years (Figure 1) including 1 patient from Australia diagnosed at 12 months based on radiographic evidence and elevated uGAG levels despite being >95th percentile for length, weight and head circumference. Another patient from Japan, also classified as experiencing overgrowth within the first year of life, was diagnosed at 3.3 years with the clinical suspicion based on other physical features associated with Morquio A.Figure 1

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Genetic Metabolic Disorders Service, The Children's Hospital at Westmead, Hawkesbury Rd & Hainsworth St, Westmead, Sydney, NSW, Australia. kaustuv.bhattacharya@health.nsw.gov.au.

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.

Show MeSH
Related in: MedlinePlus