Clinical Trial Summary
Mucopolysaccharidosis IVA (MPS IVA) (or Morquio A disease) is a rare recessive autosomal
lysosomal storage disorder caused by deficiency of N-acetylgalactosamine-6-sulfatase (GALNS)
resulting in accumulation of the glycosaminoglycans (GAGs) chondroitin-6-sulfate and keratin
sulfate (KS). Patients display progressive development of skeletal and joint abnormalities
and non-skeletal features including respiratory, cardiac, sensorial and neurological
complications. Recently, a specific treatment using enzyme replacement therapy (ERT) with
recombinant human GALNS (elosulfase alfa) has become available. A multicenter double-blind
placebo-controlled phase 3 trial (176 patients, age > 5 yrs) showed significant improvement
in endurance of 22.5 m in 6 Minute Walking Test (6MWT) distance after 24 weeks of treatment
with elosulfase alfa at 2.0 mg/kg/week as compared with placebo group. In addition to ERT, a
multidisciplinary management approach is necessary for coordinating assessment and follow-up
as well as for providing individualized supportive and symptomatic care.
The clinical presentation is highly variable from one patient to another regarding age at
onset, severity, progression rate and life expectancy. Most patients are affected with the
classical phenotype characterized by short trunk dwarfism with short neck and adult height <
1 m. Atypical phenotypes with less severe extension of skeletal manifestations, adult height
> 1m, and less frequent complications in other organs have been progressively recognized.
Clinical management differs depending on the clinical presentation of the patients but
natural history of the disease is largely unknown in atypical phenotypes. Precise and
exhaustive follow-up data are needed in such patients to increase our knowledge of this
natural history and to define the best criteria to evaluate ERT efficiency.
The investigators propose a prospective clinical study focused on a unique large series of 9
adult patients (aged from 18 to 55 years) followed in a single expert center for metabolic
disorders located at the university hospital of Bordeaux, France. Eight of these patients are
affected with atypical MPS IVA characterized by less severe evolution of the disease and
heights ranging from 135 to 176 cm (the last patient height is 102 cm). Investigators aim to
increase knowledge on the natural history of the disease in adult patients with atypical MPS
IVA, treated or not with ERT, and to develop new objective and robust clinical criteria to
evaluate the efficiency of ERT over time, particularly in patients presenting an atypical
phenotype. The entire cohort treated or not treated with ERT, will be evaluated at baseline
and every year during a 5-years period. The complete evaluation at baseline will be our
absolute priority as well as obtaining long-term and exhaustive follow up of the patients
treated with ERT (two patients of the cohort already treated, and ERT expected in three
additional patients in the next months).
The investigators designed a schedule of systematic and exhaustive assessments based on the
recommended follow up from experts panel consensus meeting (MorCAP protocol) extended to some
additional investigations including motor, cardiac and rheumatologic exams as our specific
focus.
