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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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Radiographs of a two-year-old female patient diagnosed with Hurler syndrome (MPS IH) (a-c).a) Flaring iliac wings with distal tapering; capital femoral epiphyses are not dysplastic. b) Hypoplastic L2 vertebral body with dorsal gibbus maximized at this point; inferior beaking (hook shape) throughout the lumbar vertebral bodies; posterior scalloping of the vertebral bodies in the lumbar spine. c) Short metacarpals with tapering and converging of proximal ends; diaphyseal widening through the metacarpals and phalanges; distal radius and ulnar are inclined on their planes towards each other.
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Fig5: Radiographs of a two-year-old female patient diagnosed with Hurler syndrome (MPS IH) (a-c).a) Flaring iliac wings with distal tapering; capital femoral epiphyses are not dysplastic. b) Hypoplastic L2 vertebral body with dorsal gibbus maximized at this point; inferior beaking (hook shape) throughout the lumbar vertebral bodies; posterior scalloping of the vertebral bodies in the lumbar spine. c) Short metacarpals with tapering and converging of proximal ends; diaphyseal widening through the metacarpals and phalanges; distal radius and ulnar are inclined on their planes towards each other.

Mentions: Subtle radiographic distinctions also exist between Morquio A and other MPS subtypes (Figures 4a-c, 5a-c). While the pelvis of a patient with Morquio A would have a steep acetabulum with tapering ilium distally with capital femoral epiphyseal dysplasia (Figure 4a), a patient of approximately the same age with Hurler syndrome (MPS IH) would have similar appearances but without dysplastic capital femoral epiphyses (Figure 5a). Patients with Hurler syndrome commonly have a hypoplastic L1 or L2 vertebral body, dorsal gibbus, and posterior scalloping of the vertebral bodies of the lumbar spine, yet do not have short vertebral bodies (Figure 5b), in contrast to a patient with Morquio A whose lateral thoracolumbar spine shows uniform platyspondyly with mild beaking (Figure 4b). While the phalanges of a patient with Morquio A retain its diaphyseal constriction (Figure 4c), there is diaphyseal widening through the phalanges and metacarpals for patients with Hurler syndrome (Figure 5c). As well, the joint hypermobility commonly associated with Morquio syndrome in the early stages may distinguish patients with Morquio A patients when compared with the fixed or constricted joint seen in other MPS disorders. Both lead to functional impairment but in the former, adaptations to hand function, in particular, address passive hypermobility at the wrist and decreased strength. In the latter the interventions increase range of movement [26]. This distinction is important in order to correctly manage the identified problems. In Morquio, the pathophysiology of this difference could be related to impaired chondrocyte function leading to defective growth plate architecture. Whilst some chondrocyte and collagen dysfunction has been noted in post-mortem studies of adults, conclusions cannot be drawn as no systematic prospective study has yet taken place of the children as they acquire these difficulties [27,28].Figure 4


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)

Radiographs of a two-year-old female patient diagnosed with Hurler syndrome (MPS IH) (a-c).a) Flaring iliac wings with distal tapering; capital femoral epiphyses are not dysplastic. b) Hypoplastic L2 vertebral body with dorsal gibbus maximized at this point; inferior beaking (hook shape) throughout the lumbar vertebral bodies; posterior scalloping of the vertebral bodies in the lumbar spine. c) Short metacarpals with tapering and converging of proximal ends; diaphyseal widening through the metacarpals and phalanges; distal radius and ulnar are inclined on their planes towards each other.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig5: Radiographs of a two-year-old female patient diagnosed with Hurler syndrome (MPS IH) (a-c).a) Flaring iliac wings with distal tapering; capital femoral epiphyses are not dysplastic. b) Hypoplastic L2 vertebral body with dorsal gibbus maximized at this point; inferior beaking (hook shape) throughout the lumbar vertebral bodies; posterior scalloping of the vertebral bodies in the lumbar spine. c) Short metacarpals with tapering and converging of proximal ends; diaphyseal widening through the metacarpals and phalanges; distal radius and ulnar are inclined on their planes towards each other.
Mentions: Subtle radiographic distinctions also exist between Morquio A and other MPS subtypes (Figures 4a-c, 5a-c). While the pelvis of a patient with Morquio A would have a steep acetabulum with tapering ilium distally with capital femoral epiphyseal dysplasia (Figure 4a), a patient of approximately the same age with Hurler syndrome (MPS IH) would have similar appearances but without dysplastic capital femoral epiphyses (Figure 5a). Patients with Hurler syndrome commonly have a hypoplastic L1 or L2 vertebral body, dorsal gibbus, and posterior scalloping of the vertebral bodies of the lumbar spine, yet do not have short vertebral bodies (Figure 5b), in contrast to a patient with Morquio A whose lateral thoracolumbar spine shows uniform platyspondyly with mild beaking (Figure 4b). While the phalanges of a patient with Morquio A retain its diaphyseal constriction (Figure 4c), there is diaphyseal widening through the phalanges and metacarpals for patients with Hurler syndrome (Figure 5c). As well, the joint hypermobility commonly associated with Morquio syndrome in the early stages may distinguish patients with Morquio A patients when compared with the fixed or constricted joint seen in other MPS disorders. Both lead to functional impairment but in the former, adaptations to hand function, in particular, address passive hypermobility at the wrist and decreased strength. In the latter the interventions increase range of movement [26]. This distinction is important in order to correctly manage the identified problems. In Morquio, the pathophysiology of this difference could be related to impaired chondrocyte function leading to defective growth plate architecture. Whilst some chondrocyte and collagen dysfunction has been noted in post-mortem studies of adults, conclusions cannot be drawn as no systematic prospective study has yet taken place of the children as they acquire these difficulties [27,28].Figure 4

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