Rare Disease Report

Difficulties in Morquio A Diagnoses

OCTOBER 10, 2015
Rebekah Harrison

 

 

 

 

Morquio A is a rare, progressive lysosomal storage disease that can result in serious complications for patients. Early recognition of the clinical signs and efficient diagnosis is imperative for the best, most effective treatment.

Surprisingly, the classic features of a person with Morquio A, such as skeletal and joint abnormalities and short stature, may not always be easy to recognize. A recent study observed that the average time between the appearance of first symptoms and proper diagnosis is up to 2.5 years.1 To raise awareness of this rare condition and improve the time-to-diagnosis, a symposium called

“Overcoming Challenges of Morquio A Diagnoses: The Latest from the Lab and the Clinic” was featured recently at the 2015 American Society of Human Genetics annual meeting. The speakers were Paul Harmatz, MD, University of California – San Francisco Benioff Children’s Hospital Oakland; and Timothy Wood, PhD, Greenwood Genetic Center in Greenwood, South Carolina.

What is Morquio A?

Also called mucopolysaccharidosis IV type A (MPS IVA), Morquio A is caused by a deficiency in the activity of N-acetyl-galactosamine-6-sulfatase (GALNS), an enzyme that catalyzes the breakdown of 2 glycosaminoglycans (GAGs), keratan sulfate (KS) and chondroitin-6-sulfate (C6S). It can be characterized by progressive accumulation of KS and C6S in tissues.2

The wide variety of signs and symptoms that can hinder early diagnosis are likely related to the 227 mutations in the GALNS gene that have been associated with Morquio A.

“There are no predominant mutations,” said Dr Harmatz.

Classical Morquio A patients present with marked musculoskeletal abnormalities. Most often, spinal dysplasia is diagnosed. Patients also present with short stature and joint issues such as instability and degeneration. Abnormal gait and weak hand grip are also present.

A major cause of morbidity and mortality is spinal involvement, the spectrum of which includes body anomalies, spinal canal stenosis, cervical spine subluxation and instabilty, and spinal cord compression.

“These spinal problems can predispose patients to paralysis and even death,” said Dr Harmatz.

Patients’ respiratory function may also be severely limited.

Delays in Diagnosis

There is a wide variability in clinical presentation and disease severity that can delay diagnosis of this condition.

 “MPS [IVA] patients have this principle of wide-spectrum progression over time, so you can get fooled by a patient because they are just too young to have the classical phenotype,” said Dr Harmatz.

Diagnosis is delayed up to 2.5 years [with a mean age of onset of 2.1 years with a mean age at diagnosis of 4.7 years.1 This is due to atypical/subtle symptoms and misdiagnoses.3

Classical versus Nonclassical Phenotype

Even with the variety of distinct symptoms that mark the classic phenotype of Morquio A, approximately 25% of patients who have nonclassical Morquio A can take years to properly diagnosis. One study indicated that those patients may not be diagnosed until late childhood, early teens, or even adulthood.3

The Many Faces of Morquio A




Diagnosis = Early Suspicion + A Good Radiologist

In many cases, the radiologist reading an x-ray will suspect Morquio A.

“X-rays are usually the best thing to lead you towards Morquio A. If your pediatric radiologist can just say ‘this is not normal’ on a lateral spine or hip x-ray, that will get you to the lab for screening and then hopefully a diagnosis,” said Dr Harmatz.

Early diagnosis can lead to proper treatment and better quality of life.

While many symptoms are present in Morquio A patients, the ones that are most important to the patient often relate to mobility. “We really want to keep these people mobile,” said Dr Harmatz. “When they lose it, their quality of life decreases. Mobility is a key goal in early diagnosis. Mobility is the goal of our program.”

References

  1. 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(2):165-174.
  2. Neufeld EF, Muenzer J. The mucopolysaccharidoses. In: Valle D, Beaudet AL, Vogelstein B, et al, eds. The Online Metabolic & Molecular Bases of Inherited Disease. TK, Germany: The McGraw-Hill Companies; 2001-2006.
  3. Bhattacharya K, Balasubramaniam S, Choy YS, et al. Overcoming the barriers to diagnosis of Morquio A syndrome. Orphanet J Rare Diseases. 2014;9:192.
Images courtesy of Dr Paul Hamartz

 

 

 



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