Rare Disease Report

Clinicians Not Diagnosing Morquio A Syndrome Quickly Enough?

DECEMBER 02, 2014
James Radke

With the recent approval of Vimizim (elosulfase alfa) to treat patients with Morquio A syndrome, these children now have a chance to lead longer, healthier lives, especially if they are diagnosed quickly before some of the irreversible complications of the disease have a chance to progress.
Unfortunately, it is still taking several years for patients with Morquio A syndrome to be diagnosed. In a recent study, Bhattacharya and colleagues report that the time of first symptoms to diagnosis can be 3 to 4 years. 
In their study based in the Asia Pacific region, Bhattacharya et al looked at the medical records of 18 patients with Morquio A syndrome and found that the mean age of symptom onset was 77.1 months while mean age of diagnosis was 113.8 months.
As with many rare diseases, patients with the more common symptoms associated with the more severe forms of the syndrome are diagnosed more quickly. However, for many patients, the symptoms are not as obvious.

The study found that delayed diagnosis was due to:
  • Atypical symptoms (n=5, 28%)
  • Subtle symptoms (n=4, 22%)
  • Symptoms commonly associated with other diseases (n=4, 22%)
  • False-negative urine glycosaminoglycan analysis (n=4, 22%)
 Misdiagnosis was also fairly common with 11 (61%) patients at some point being misdiagnosed as having:
  • Spondyloepiphyseal dysplasia (n=5, 28%)
  • Gibbus/kyphosis (n=5, 28%)
  • Scoliosis (n=3, 17%)
 Key to early diagnosis was good radiographic features showing common skeletal features of Morquio A. The paper concludes that better awareness and education of early symptoms of Morquio A syndrome are needed. In their discussion, the authors wrote:

Raising clinical suspicion of Morquio A amongst clinicians frequently encountering these patients in the pre-diagnostic stage is necessary to ensure early diagnosis and treatment.  However, sparse data exist on the natural history of Morquio A, especially in early childhood.  Skeletal symptoms such as joint laxity, gibbus, cervical spine stenosis and/or cord compression, kyphoscoliosis, pectus carinatum, bilateral hip dysplasia, progressive genu valgum and short stature of unknown etiology should raise suspicion of Morquio A. This is especially true when in combination with some accompanying signs and symptoms of MPS such as macrocephaly, corneal clouding, loss of visual acuity, hearing impairment, recurrent middle ear infections, recurrent respiratory tract infection, valvular heart disease, rhythm abnormalities due to conduction defects, and recurrent inguinal or umbilical hernia."

 The authors cautioned:

“that 5 (28%) of the patients in our cohort experienced presenting signs and symptoms that were not previously reported as typical of Morquio A and may provide
Additional clues to consider during the clinical diagnosis.”

 As with many ultra rare lysosomal diseases, the natural history of Morquio A is not well established and the large variance in symptomology makes it difficult to recognized some of the symptoms early. Hopefully, more education and awareness will improve this dilemma.

Symptoms to Look For

Some of the common manifestations of Morquio A Syndrome that raise clinical suspicion include:
  • Abnormal gait, joint laxity, and leg. Hip, and/or back pain
  • Short stature, genu valgum, kyphosis/gibbus, odontoid hypoplasia pectus carinatam/excavatum, and other skeletal abnormalities of the hip, wrists, ankles, and legs
  • Cervical spine instability
  • Short neck, prominent forehead
  • Respiratory manifestations (limited endurance, sleep apnea, snoring)
  • Frequent ear and/or respiratory infections
  • Conductive and sensoneuronal hearing loss when experiencing other symptoms
  • Corneal clouding
  • Cardiac valve abnormalities
  • Dental abnormalities
Less common manifestations that should raise suspicion of Morquio A Syndrome and/or not exclude the syndrome include:
  • Accelerated growth in infancy
  • Cardiac conduction abnormality
  • Splenomegaly
  • Truncal hypotonia
  • Harrison sulcus
  • Growth hormone deficiency
  • Reversed Madelung deforminty

About Morquio A Syndrome

Morquio A syndrome is an inherited lysosomal storage disorder in which patients are missing the enzyme N-acetyl-galactosamine-6-sulfatase. The net result is an accumulation of glycosaminoglycans throughout the body and they have features common to many MPS patients (course facial features, abnormal bone development, short stature) as well as a plethora of other problems as gycosaminoglycans accumulate in various organs.

Morquio A is an ultra-rare condition. It is estimated there are approximately 520 – 800  patients in the United States.


Bhattacharya B, balasubramaniam S, Choy YS, et al. Overcoming the barriers to diagnosis of Morquio A syndrome. Orphanet J Rare Dis. 20014.9:192. doi:10.1186/s13023-014-0192-7

image obtained from the Open Source article by Bhattacharya and collegues in the Orphanet Journal of Rare Diseases.

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