Approximately 25% of patients with Morquio A syndrome do not have the classic signs and symptoms of the condition and may go years before being properly diagnosed. To illustrate how such a patient can go undetected within the medical community for so long a time, a case study of a nonclassical Morquio A phenotype was recently presented during the 2015 American Society of Human Genetics meeting in Baltimore, Maryland. Paul Harmatz, MD, of the University of California – San Francisco (UCSF) Benioff Children’s Hospital Oakland, spoke on “Overcoming Challenges of Morquio A Diagnosis: The Latest from the Lab and the Clinic.”
What is Morquio A?
Also referred to as mucopolysaccharidosis IV type A, Morquio A is an autosomal recessive lysosomal storage disorder. It is caused by deficient 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), and is characterized by progressive accumulation of KS and C6S in tissues. Symptoms include skeletal dysplasia, spinal cord compression, and hearing loss.1
The first hint that the patient may have Morquio A occurred in 2007; the 8-year-old boy had an orthopedic consultation regarding limb length discrepancy, ligamentous laxity, and bilateral subluxing patella. Morquio A was not suspected, however.
At age 11 years, the boy presented to a skeletal dysplasia clinic after having back and hip pain for 3 years. Upon urinalysis, his urine GAG levels were found to be mildly elevated.
At age 13 years, the patient was examined upon suffering foot pain after walking 1 mile and constant right hip pain.
His legs and ankles were often swollen and he used a manual wheelchair intermittently. He had mild kyphosis with a waddle gait, but he was of normal height and mental status. X-rays revealed dysplastic hips (see image).1
At this point, Dr Harmatz was consulted, and he sent standard labs to Greenwood Genetics. The patient’s urine GAG was slightly elevated
, while electrophoresis revealed a faint keratan sulfate band. His enzyme panel was normal with the exception of low GALNS.
“We asked for the molecular mutation for confirmation,” said Dr Harmatz.
Dr Harmatz also conducted a number of baseline evaluations that should, he said, be standard of care for Morquio A patients prior to beginning treatment, including testing of cardiovascular and respiratory function and examination of the spine and eyes. Walking, climbing, and hand dexterity tests were also performed.
Dr Harmatz noted that once a diagnosis is made, it is important to capture as many baseline measures as possible. Since there is a great deal of heterogenity within the population, without baselines it can be difficult to ascertain if a treatment is working or not.
Patient conducting the 6-minute walk test, the 3-minute stair test, and the 16-peg hand test.
Enzyme Replacement Therapy
Following his diagnosis of Morquio A, the patient was placed on elosulfase alfa (Vimizim) enzyme replacement therapy. Prior to treatment, the patient’s median urine KS levels were 6.17 ug/mg creatinine, and after 6 months of treatment, his urine KS levels had dropped 51% (range of 2.47 to 3.79 μ
g/mg creatinine over a 2-month period).
There were also significant, albeit difficult to quantify, improvements in his daily life. For instance, “he walked the entire car show at the Oakland Coliseum,” said Dr Harmatz. “His parents didn’t imagine him walking from even the car to the coliseum without his wheelchair before treatment.”
Harmatz P, Mengel KE, Giugliani R, et al. The Morquio A Clinical Assessment Program: baseline results illustrating progressive, multisystemic clinical impairments in Morquio A subjects. Mol Genet Metab.
Images courtesy of Paul Harmatz, MD, UCSF Benioff Children’s Hospital, Oakland.