Study to Detect Unrecognized Mucopolysaccharidosis in Children Visiting Rheumatology, Hand or Skeletal Dysplasia Clinics

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.

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.