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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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Pseudoachondroplasia in a four-year-old boy, who presented with genu vara and short stature (a-d).a) Pelvis shows small and round capital femoral epiphyses with an underdeveloped and irregularly shaped lower portion of the ilium that results in horizontal appearance of the acetabular roofs. b) The lower extremity radiograph shows genu vara with wide and strikingly irregular distal femoral metaphases; epiphyses at the knees that are dysplastic and triangular in shape in the femoral ends that partly invaginated into the cupping of the femoral metaphases; dysplastic metaphyseal change is also noted in the distal tibiae. c) The spine radiograph shows mild platyspondyly and considerable irregularity of the upper and lower endplates of the vertebral bodies; mid-central tongue in pseudoachondroplasia associated with apophyseal dysplasia of the vertebral bodies along the upper and lower endplates, resulting in biconvex configuration. d) Short metacarpals with metaphyseal cupping and irregularity and small, round epiphyses; short and stubby phalangeal bones with mild metaphyseal cupping; delayed ossification of the small and irregular carpal bones with apparent metaphyseal widening and irregularity at the distal radius and ulna.
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Fig3: Pseudoachondroplasia in a four-year-old boy, who presented with genu vara and short stature (a-d).a) Pelvis shows small and round capital femoral epiphyses with an underdeveloped and irregularly shaped lower portion of the ilium that results in horizontal appearance of the acetabular roofs. b) The lower extremity radiograph shows genu vara with wide and strikingly irregular distal femoral metaphases; epiphyses at the knees that are dysplastic and triangular in shape in the femoral ends that partly invaginated into the cupping of the femoral metaphases; dysplastic metaphyseal change is also noted in the distal tibiae. c) The spine radiograph shows mild platyspondyly and considerable irregularity of the upper and lower endplates of the vertebral bodies; mid-central tongue in pseudoachondroplasia associated with apophyseal dysplasia of the vertebral bodies along the upper and lower endplates, resulting in biconvex configuration. d) Short metacarpals with metaphyseal cupping and irregularity and small, round epiphyses; short and stubby phalangeal bones with mild metaphyseal cupping; delayed ossification of the small and irregular carpal bones with apparent metaphyseal widening and irregularity at the distal radius and ulna.

Mentions: Diagnosis of SED based solely on the presence of scoliosis, kyphosis, and/or a single superior notched vertebra without the presence of either platyspondyly or superior/inferior humping of vertebral bodies is not consistent with any known form of SED [24] and consideration of an alternative diagnosis such as Morquio A is prudent. Although patients of non-classical phenotype may not have the typical, pronounced manifestations that would lead to a clinical suspicion of a MPS disease [23-25], awareness of the unique and distinguishing features of orthopedic diseases may contribute to earlier diagnosis of Morquio A. There are subtle radiographic differences between Morquio A (Figure 2a-d) and other skeletal dysplasia, such as pseudoachondroplasia (Figure 3a-d) and SED (image not shown), which could help clinicians distinguish between these diagnoses. The pelvis and knee changes observed in patients with Morquio A (Figures 2a and 2b) differ from those with pseudoachondroplasia (Figures 3a and 3b). The spine of a patient with pseudoachondroplasia (Figure 3c) shows mild platyspondyly and considerable irregularity of the upper and lower endplates of the vertebral bodies. The anterior protrusion of the central aspects of the vertebral bodies may mimic to the middle beaking in Morquio A (Figure 2c), but this mid-central tongue in pseudoachondroplasia is associated with apophyseal dysplasia of the vertebral bodies along the upper and lower endplates, resulting in biconvex configuration (Figure 3c).Figure 2


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)

Pseudoachondroplasia in a four-year-old boy, who presented with genu vara and short stature (a-d).a) Pelvis shows small and round capital femoral epiphyses with an underdeveloped and irregularly shaped lower portion of the ilium that results in horizontal appearance of the acetabular roofs. b) The lower extremity radiograph shows genu vara with wide and strikingly irregular distal femoral metaphases; epiphyses at the knees that are dysplastic and triangular in shape in the femoral ends that partly invaginated into the cupping of the femoral metaphases; dysplastic metaphyseal change is also noted in the distal tibiae. c) The spine radiograph shows mild platyspondyly and considerable irregularity of the upper and lower endplates of the vertebral bodies; mid-central tongue in pseudoachondroplasia associated with apophyseal dysplasia of the vertebral bodies along the upper and lower endplates, resulting in biconvex configuration. d) Short metacarpals with metaphyseal cupping and irregularity and small, round epiphyses; short and stubby phalangeal bones with mild metaphyseal cupping; delayed ossification of the small and irregular carpal bones with apparent metaphyseal widening and irregularity at the distal radius and ulna.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig3: Pseudoachondroplasia in a four-year-old boy, who presented with genu vara and short stature (a-d).a) Pelvis shows small and round capital femoral epiphyses with an underdeveloped and irregularly shaped lower portion of the ilium that results in horizontal appearance of the acetabular roofs. b) The lower extremity radiograph shows genu vara with wide and strikingly irregular distal femoral metaphases; epiphyses at the knees that are dysplastic and triangular in shape in the femoral ends that partly invaginated into the cupping of the femoral metaphases; dysplastic metaphyseal change is also noted in the distal tibiae. c) The spine radiograph shows mild platyspondyly and considerable irregularity of the upper and lower endplates of the vertebral bodies; mid-central tongue in pseudoachondroplasia associated with apophyseal dysplasia of the vertebral bodies along the upper and lower endplates, resulting in biconvex configuration. d) Short metacarpals with metaphyseal cupping and irregularity and small, round epiphyses; short and stubby phalangeal bones with mild metaphyseal cupping; delayed ossification of the small and irregular carpal bones with apparent metaphyseal widening and irregularity at the distal radius and ulna.
Mentions: Diagnosis of SED based solely on the presence of scoliosis, kyphosis, and/or a single superior notched vertebra without the presence of either platyspondyly or superior/inferior humping of vertebral bodies is not consistent with any known form of SED [24] and consideration of an alternative diagnosis such as Morquio A is prudent. Although patients of non-classical phenotype may not have the typical, pronounced manifestations that would lead to a clinical suspicion of a MPS disease [23-25], awareness of the unique and distinguishing features of orthopedic diseases may contribute to earlier diagnosis of Morquio A. There are subtle radiographic differences between Morquio A (Figure 2a-d) and other skeletal dysplasia, such as pseudoachondroplasia (Figure 3a-d) and SED (image not shown), which could help clinicians distinguish between these diagnoses. The pelvis and knee changes observed in patients with Morquio A (Figures 2a and 2b) differ from those with pseudoachondroplasia (Figures 3a and 3b). The spine of a patient with pseudoachondroplasia (Figure 3c) shows mild platyspondyly and considerable irregularity of the upper and lower endplates of the vertebral bodies. The anterior protrusion of the central aspects of the vertebral bodies may mimic to the middle beaking in Morquio A (Figure 2c), but this mid-central tongue in pseudoachondroplasia is associated with apophyseal dysplasia of the vertebral bodies along the upper and lower endplates, resulting in biconvex configuration (Figure 3c).Figure 2

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