Clinical trial NCT01675674: Study to Detect Unrecognized Mucopolysaccharidosis in Children Visiting Rheumatology, Hand or Skeletal Dysplasia Clinics
Official title: Unrecognized Mucopolysaccharidosis I, II, IVA, and VI in the Pediatric Rheumatology Population
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Mucopolysaccharidoses
Mucopolysaccharidosis I
Mucopolysaccharidosis II
Mucopolysaccharidosis IV
Mucopolysaccharidosis VI
Keywords: Mucopolysaccharidoses
Prevalence
Pediatric
Rheumatology
Mucopolysaccharidosis I
Mucopolysaccharidosis II
Mucopolysaccharidosis IV
Mucopolysaccharidosis VI
Lead sponsor: National MPS Society
Sponsor class: OTHER
Collaborators: name: MediResource Inc.
First posted: 2012-08-30
Enrollment: 3000
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Sampling method: NON_PROBABILITY_SAMPLE
Study population: For the prospective study, subjects will be drawn from all children (aged 6 months to 18 years) with a history of presenting to selected clinics (pediatric rheumatology, pediatric hand, or skeletal dysplasia clinic), with at least ONE "highly suspicious" symptom or at least TWO "less suspicious" symptoms that may be indicative of an MPS disorder (see inclusion criteria).

For the retrospective chart review, subjects will be drawn from all children who were 6 months to 18 years of age at the time of first presentation to selected clinics (pediatric rheumatology, pediatric hand, or skeletal dysplasia clinic), with at least ONE "highly suspicious" symptom or at least TWO "less suspicious" symptoms that may be indicative of an MPS disorder (see inclusion criteria).

Brief summary: This study is being done to learn how many children and young adults who come to pediatric rheumatology clinics may have mucopolysaccharidosis (MPS). The study tests for 4 of the types of MPS: I, II, IVA, and VI. This can help researchers decide whether to create a screening program for MPS at pediatric rheumatology clinics. This study is being done in rheumatology clinics because the first symptoms of MPS are often joint problems such as stiff joints, and rheumatologists may be the first doctors that a patient with MPS visits. The study will also evaluate the utility of dried blood spot testing for MPS.

Detailed description: MPS, or mucopolysaccharidosis (mew-co-paw-lee-sack-a-rid-o-sis), disorders are a group of rare inherited diseases that affect about 1 in every 25,000 people in the United States. There are 7 MPS disorders: MPS I (Hurler, Hurler-Scheie, and Scheie syndromes), II (Hunter syndrome), III (Sanfilippo syndrome), IV (Morquio syndrome), VI (Maroteaux-Lamy syndrome), VII (Sly syndrome), and IX (no other name). In people who have MPS, the body cannot break down certain materials in the body's cells. These materials then build up in the cells, causing problems such as stiff joints, misshapen bones, curled hands and reduced hand function, frequent ear infections, vision and hearing problems, "thickened" facial features, and heart problems. Getting access to diagnosis and treatment can help make MPS easier to manage; but unfortunately, people with MPS may go undiagnosed for many years.

This study is being done to learn how many children and young adults who come to pediatric rheumatology clinics may have mucopolysaccharidosis (MPS). The study tests for 4 of the types of MPS: I, II, IVA, and VI. This can help researchers decide whether to create a screening program for MPS at pediatric rheumatology clinics. This study is being done in rheumatology clinics because the first symptoms of MPS are often joint problems such as stiff joints, and rheumatologists may be the first doctors that a patient with MPS visits.

The study will use dried blood spot (DBS) testing to screen for these types of MPS. It will also use a survey to evaluate the utility and convenience of dried blood spot testing for MPS.

Eligibility criteria: Inclusion Criteria:

1. History of presenting to the pediatric rheumatology, pediatric hand, or skeletal dysplasia clinic with at least ONE "highly suspicious" symptom or at least TWO "less suspicious" symptoms that may be indicative of an MPS disorder (see below):

   Highly suspicious symptoms:
   * characteristic facial features
   * hearing loss
   * corneal clouding
   * cardiac manifestations
   * dysostosis multiplex
   * hepatosplenomegaly
   * spinal cord compression
   * hydrocephalus
   * carpal tunnel syndrome
   * delayed mental development or regression in mental development

   Less suspicious symptoms:
   * short stature
   * extensive Mongolian spots
   * sleep apnea
   * copious nasal discharge
   * recurrent otitis media, ear fluid that will not drain, or the presence of ear tubes
   * frequent upper respiratory tract infections
   * joint stiffness or limited range of motion
   * hand problems (Claw hands or reduced hand function)
   * hernia (inguinal or umbilical)
   * abnormally shaped teeth
   * dental cysts
   * tooth abscess
2. Age of at least 6 months.
3. Age under 18 years at time of initial clinic presentation.
4. Written, signed, and dated informed consent obtained from the subject (if 18 years of age) or the subject's parents (if under 18). Written, dated, and signed assent from children is also required at some centers.

Exclusion Criteria:

1. Under 6 months of age.
2. Over 18 years of age at initial clinic presentation.
3. Patients who have had confirmation of an MPS disorder by biochemical analysis and/or by molecular biology.
4. Patients for whom MPS enzyme activity tests (i.e., enzyme levels tested in fibroblasts, leukocytes, serum, or blood spots) have already been performed, and for which the result was normal. (Patients who have been screened for MPS through urinary GAG and tested normal will not be excluded from the study.)
5. Written informed consent not available.
6. Subject unwilling or unable to provide the necessary blood spot for analysis.
7. Any other condition that would, in the opinion of the investigator, interfere with the participant's ability to provide informed consent, comply with study instructions, or possibly confound interpretation of study results.

Primary outcomes:
measure: Incidence of previously unrecognized MPS I, II, IVA, and VI in children presenting to pediatric rheumatology, hand, or skeletal dysplasia clinics
timeFrame: At study completion (approximately 18 months after the beginning of the study)
Secondary outcomes:
measure: Utility of DBS testing to screen for MPS in pediatric patients
timeFrame: At study completion (approximately 18 months after the beginning of the study)
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: University of Medicine and Dentistry of New Jersey
state: New Jersey
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
Study officials:
affiliation: Chief, Division of Pediatric Rheumatology, Hospital for Special Surgery; Professor of Clinical Pediatrics, Cornell University
name: Thomas JA Lehman, MD
role: PRINCIPAL_INVESTIGATOR
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