Home > Diagnoses & Conditions > Mucopolysaccharidosis Type I > Ongoing Assessment
Mucopolysaccharidosis Type I - Ongoing Assessment
Overview
Because of the extensive and wide-spread organ system involvement, every child with mucopolysaccharidosis type I (MPS I) should receive multidisciplinary and subspecialty care from a center with expertise in lysosomal storage disorders (LSDs). The primary care physician should serve as the child’s medical home, collaborating with various subspecialists and providing support to the entire family. Given the rapid progression of the disease, regular visits (a few times a year) are indicated in children with severe MPS I. Those with the attenuated forms may also benefit from frequent visits, though the need will depend upon their clinical status.Screening
Screening for MPS I is not currently recommended unless a family member is affected. When there is suspicion of MPS I, measurement of urinary excretion of glycosaminoglycans (GAGs) is a non-invasive way to rule out the condition. An elevation of urinary GAGs is a strong indication of an underlying lysosomal storage disorder. The pattern of GAG excretion should be compared to the patterns seen in each of the MPS disorders. If consistent with an MPS, confirmatory testing should be performed. Newborn screening is under consideration in a number of states and could be added to the Newborn Screen Panel in the future.The clinical manifestations of MPS I may not become evident until the child is a few months to a few years of age, there fore, screening for MPS I in early childhood is not indicated. Some of the earliest presenting features of MPS I may be inguinal or umbilical hernia, coarsening of facial features, and enlargement of the liver and spleen. If a combination of these features is suspected, measurement of urinary excretion of glycosaminoglycans (GAGs) is a noninvasive way to rule out the condition. An elevation of urinary GAGs is a strong indication of an underlying lysosomal storage disorder. The pattern of GAG excretion should be compared to the patterns seen in each of the MPS disorders. If consistent with an MPS, confirmatory testing should be performed.
Any sibling of an individual with confirmed MPS I should have an enzyme screening and/or genetic testing (if the mutations in the family have already been identified) at birth so that treatment may be discussed and initiated as early as possible.
Carrier screening of parents and other family members via enzyme analysis is not recommended since there can be significant overlap in enzyme levels between carriers and non-carriers. Carrier screening via molecular genetic testing is indicated in family members if the mutations within the family are known. Whole gene sequencing to identify carriers in the general population is not indicated.
Diagnostic Criteria
The diagnosis of MPS I is established by:- Confirming deficiency of α-L-iduronidase in peripheral blood leukocytes or cultured fibroblasts.
- Molecular genetic testing for mutations in IDUA, the gene that encodes α-L-iduronidase, can be used for confirmatory diagnostic testing.
Pearls And Alerts
Airway management during anesthesia in individuals with MPS I is difficult and should be performed by anesthesiologists aware of the significant risks associated with sedation, such as airway compromise and cervical joint limitation secondary to GAG accumulation.
A rapid increase in head circumference, acute behavioral changes, or headaches could be signs of hydrocephalus. If they are present, a lumbar puncture with measurement of opening pressure of cerebrospinal fluid (CSF) is the preferred method for assessing the degree of pressure elevation because the ventricles can be resistant to volume changes with increased pressure.
Hand tingling and pain could represent carpal tunnel syndrome with nerve entrapment.
Because of the risk for spinal compression, parents/patients should be instructed to avoid "high risk" activities, such as contact sports, and should be cautioned about manipulation of the cervical spine.
History And Examination
175 KB)
MPS Assessment Schedule. Children with MPS I have multi-system organ involvement and growth and developmental delays, making management of their symptoms very complex. Treatment options depend upon the age of diagnosis and clinical severity at the time of diagnosis. A thorough discussion regarding the benefits, limitations, and risks of each therapeutic option should be addressed with the family and healthcare providers soon after the diagnosis is made to improve the long-term outcome.
Interim History
It is important to assess ask about symptoms associated with common findings in MPS I. Typical clinical findings at various ages include:- 0-6 months:
- chronic rhinitis
- recurrent otitis media or "glue ear"
- umbilical or inguinal hernia
- above normal growth and head size
- 6 mos. - 12 yrs:
- distinctive facial gestalt, with coarsening over time,
- hepatosplenomegaly
- skeletal deformities
- joint stiffness
- developmental delay
- corneal clouding
- chronic rhinitis
- recurrent otitis media or "glue ear"
- 12+ years:
- corneal clouding
- joint stiffness
- valvular heart disease
Developmental and Educational Progress
Achievement of developmental milestones should be closely monitored, especially in children with Hurler syndrome, as this will help determine which treatment option(s) the child may qualify and be eligible for.Children with severe MPS I may have normal early developmental; however all children who are not treated will eventually have severe global developmental delays with regression and mental retardation.
Individuals with the attenuated forms of MPS I may have normal to mildly delayed development. Intelligence in individuals with attenuated MPS I can range from mild learning disabilities to normal cognition. Acute changes in cognition or mental status should be promptly evaluated as this could represent increased intracranial pressure due to hydrocephalus.
Social and Family Functioning
Ask about the child's social abilities and interactions with other children, and about family functioning, including the availability of resources and supports from community groups and extended family.Physical Exam
Growth Parameters
Children with severe MPS I may have above normal growth and head circumference in the first 6 months of life, however, look for growth to plateau and cessation of linear growth by three years. Assess weight and length/height.Vital Signs
Pursue any respiratory distress, with concern over aspiration, cardiac failure, or respiratory muscle compromise.General
Children with MPS I generally have coarsening of facial features resulting in a remarkably consistent appearance, including a short nose, flat face, thick lips, and large head (relatively elongated front to back with a prominent forehead). The eye sockets are shallow, the eyes protrude slightly, and the tongue is large. Body hair is coarse and abundant. Patients have protruding bellies and joint contractures which causes them to stand and walk with a bent-over stance. In milder forms of MPS I, patients have a stocky build, a trunk that is shorter than the limbs, and a shortened, stiff neck, but normal facial features.HEENT
Chronic and recurrent ear infections are common. Look for upper airway obstruction, since the trachea becomes narrowed and may be floppy or softer than usual due to abnormal cartilage rings. Assess swallowing.Document the progression of corneal clouding which occurs in all individuals with MPS I. Examine optic nerves for compression and atrophy.
Examine the mouth for signs of infection and decay. Irritability, crying, and restlessness may be the only sign of an infected tooth in a child with severe MPS.
Abdomen
Protruding abdomen and inguinal or umbilical hernias may be present. Hepatosplenomegaly is common.Extremities
Assess for joint stiffness (elbows, shoulders, hands) and contractures (initially present in the fingers, resulting in the characteristic "claw-hand"); limited hip abduction and genu valgum. Assess grip strength and thenar muscle atrophy, related to carpal tunnel syndrome.Neurologic Exam
Progressive compression of the spinal cord with resulting cervical myelopathy is relatively common in older individuals with attenuated MPS I. Communicating hydrocephalus may occur without ventriculomegaly, due to the thickened arachnoid membrane. Presence of acute behavioral changes, headaches, and vomiting warrant an evaluation of hydrocephalus.Testing
Sensory Testing
Follow visual acuity on a regular basis, including peripheral vision. Hearing should be tested if any signs of hearing loss are present or there have been persistent ear infections.Laboratory Testing
Serial measurements of urinary GAGs can be used as an objective measure to monitor the effects of enzyme replacement therapy and/or stem cell transplantation.Imaging and EEG
Brain and spine imaging with MRI should be performed every two years to assess hydrocephalus and spine stability. If indicated, ventriculoperitoneal shunting generally improves quality of life. Nerve conduction studies to assess possible carpal tunnel syndrome (tendon entrapment).Other Testing
See also Recommended Schedule of Assessments for MPS I Patients (MPS I Registry) ( 175 KB)
.
- Annual ophthalmology assessments should include measurement of visual acuity and intraocular pressure, slit lamp examination of the cornea, and electroretinography (ERG). Assessment of optic nerve for signs of intracranial pressure
- Annual sleep assessments, with sleep studies as needed, to identify the presence of sleep apnea
- Pulmonary function tests every six months
- Dental exam every six months
- Audiology exam year to determine the degree and cause of hearing impairment
Subspecialist Collaborations and Other Resources
The role of subspecialists in the care of children with MPS I is crucial, given the breadth of organ system involvement in these children. Collaboration among the primary care provider, subspecialists, and family are essential in improving quality of care to these patients.
Audiology (see Services below for relevant providers)
At the time of diagnosis and yearly to determine the degree, cause, and progression of hearing impairment.
Behavioral Pediatrics (see Services below for relevant providers)
As needed to help families cope with obstinate and immature behavior patterns and establish appropriate expectations for appropriate cognitive level for function.
Pediatric Cardiology (see Services below for relevant providers)
At diagnosis and every two years for evaluation, echocardiogram, and an ECG to monitor valvular involvement and cardiac function.
Pediatric Gastroenterology (see Services below for relevant providers)
Every two years to follow liver and spleen size and function; these can be used as an objective measure of the efficacy of enzyme replacement therapy during the first few months of treatment. May be helpful to assess and manage constipation and hernias.
Pediatric Genetics (see Services below for relevant providers)
Annually to assess status and appropriate interventions, and to assist in care coordination. Geneticists generally have the most clinical experience with MPS I.
Pediatric Genetic Counseling (see Services below for relevant providers)
Genetic counselors can be very helpful to families in understanding the condition and its inheritance, impact on other family members and future childbearing. Genetic counselors are often very knowledgeable about community resources and family support.
Pediatric Neurology (see Services below for relevant providers)
Every two years; may include an MRI of the brain and the spine, and assessment of hydrocephalus and spine stability. If indicated, ventriculoperitoneal shunting generally improves quality of life. Nerve conduction studies to assess possible carpal tunnel syndrome (tendon entrapment).
Pediatric Ophthalmology (see Services below for relevant providers)
At diagnosis and annual assessments should include measurement of visual acuity and intraocular pressure, slit lamp examination of the cornea, and electroretinography (ERG). Assessment of optic nerve for signs of intracranial pressure.
Pediatric Otolaryngology (see Services below for relevant providers)
As clinically indicated for evaluation or for tonsillectomy and adenoidectomy to decrease upper airway obstruction.
Pediatric Pulmonology (see Services below for relevant providers)
Every six months for pulmonary function tests.
Pediatric Orthopedics (see Services below for relevant providers)
Every year, or as indicated for assessment of spine, hips, knees, carpal tunnel, and gait.
Pediatric Physical Medicine & Rehab (see Services below for relevant providers)
As clinically indicated. Range of motion exercises appear to offer some benefits in preserving joint function, and should be started early. For evaluation and treatment of carpal tunnel syndrome. If possible, it is best to find someone who specializes in hand therapy.
Developmental Pediatrics (see Services below for relevant providers)
At the time of diagnosis and at least every two years to establish baseline parameters and begin early intervention.
General Dentistry for CSHCN (see Services below for relevant providers)
Every six months; regular dental care is essential. Even with excellent care, abscesses can develop due to abnormal formation of the teeth.
Clinical Classification
Severe MPS I (formerly Hurler syndrome): Infants may appear normal at birth. Coarsening of facial features and enlargement of the liver and spleen occurs over the first few months. If untreated, death occurs in first decade. The following features are usually present at an early age:- skeletal deformities
- obstructive airway disease
- progressive and severe physical problems
- communicating hydrocephalus
- limited language ability and progressive mental deterioration
- hepatosplenomegaly
- recurrent ear/nose infections
Attenuated (Formerly Hurler-Scheie syndrome): If development is normal at 24 months of age and moderate somatic involvement is evident (mild coarsening, little skeletal involvement), individuals are classified as having intermediate severity. The onset of symptoms tends to occur between three and eight years of age. Developmental delay may be present to a lesser extent, however rapid and progressive cognitive decline is not characteristic of the attenuated forms. If intellectual decline is present, it tends to follow a more gradual course occurring at a later age and over a longer period of time. Cardiac involvement and upper respiratory tract obstruction contribute to mortality (often in teens or early twenties) in these individuals. Individuals with intermediate MPS I have progressive somatic involvement, including:
- dysostosis multiplex
- arthropathy
- corneal clouding
- joint stiffness
- deafness
- cardiac involvement, including valvular heart disease
- spinal cord compression
- obstructive airway disease
Attenuated (formerly Scheie syndrome): Often diagnosed in adolescence or young adulthood, individuals generally have normal intellect, stature, and lifespan. Major clinical manifestations are:
- corneal clouding
- sleep apnea
- arthropathy and joint stiffness
- carpal tunnel syndrome and other nerve entrapment (such as cervical cord compression)
- valvular disease
- visual impairment
- mild facial coarseness
The overlap of attenuated forms of MPS I makes it difficult to separate Scheie syndrome from Hurler-Scheie syndrome. It may be easier to reflect the continuum and simply state either more- or less-attenuated, primarily based on age of clinical presentation.
Resources
Information & Support
For Professionals
Mucopolysaccharidosis Type I (GeneReviews)
An excellent review of MPS I includes genetics, clinical description, management, resources and references from the GeneReviews
Web site funded by the National Institutes of Health.
Hurler syndrome (OMIM)
A very detailed description of Hurler syndrome, its genetics, clinical features, diagnosis, and treatment; from Online Mendelian
Inheritance in Man (OMIM), from the National Center for Biotechnology Information.
For Parents and Patients
Support
National MPS Society
Provides information about the disorder, research, support for families, fund raising, and efforts to increase public awareness
about MPS and related disorders. Allows users to contact and communicate directly with other parents/patients.
Hide & Seek Foundation
"Hide & Seek is a community of people dedicated to finding treatments and cures for a devastating genetic condition called
Lysosomal Disease."
LysoLife Community
"The LysoLife Community connects families, friends and caregivers for support and inspiration. The LysoLife Community is sponsored
by the Hide & Seek Foundation in partnership with Inspire."
Mucopolysaccharidosis syndromes resources (KUMC)
A list of international resources for patients/families; from the University of Kansas Medical Center, Medical Genetics -
Genetics and Rare Conditions Site.
General
Mucopolysaccharidosis Type I (Genetics Home Reference)
Excellent overview of MPS I for families/patients, from Genetics Home Reference, a service of the National Library of Medicine.
Includes links for more consumer-level information and support.
Mucopolysaccharidoses Fact Sheet
The National Institute of Neurological Disorders and Strokes (NINDS) provides a fact sheet addresing signs and symptoms, risks,
types, treatments, research and resources.
Hurler syndrome (MedlinePlus Encyclopedia)
Brief overview and links, from the National Library of Medicine and National Institutes of Health.
Practice Guidelines
175 KB)
.
Muenzer J, Wraith JE, Clarke LA.
Mucopolysaccharidosis I: management and treatment guidelines.
Pediatrics.
2009;123(1):19-29.
PubMed abstract
Patient Education
National MPS Society Booklets
More than 10 booklets (large files) about mucopolysaccharidoses and related diseases for patients, families, and providers;
includes information about MPS I, II, III, IV, VI, VII; ML II/III; daily living; anesthesia; resources, and more.
National MPS Society Fact Sheets
More than 25 fact sheets about mucopolysaccharidoses and related diseases for patients, families, and providers; topics include
cardiac problems, caregiver support, family coping strategies, melatonin, transplants, pamidronate, tube feedings, stem cell
transplants, and more.
Tools
Recommended Schedule of Assessments for MPS I Patients (MPS I Registry)
( 175 KB)
Detailed guide to ongoing assessments prepared to support the international MPS I Registry.
Services
General Dentistry for CSHCN
See all General Dentistry for CSHCN services providers (121) in our database.
Pediatric Gastroenterology
See all Pediatric Gastroenterology services providers (2) in our database.
Pediatric Genetic Counseling
See all Pediatric Genetic Counseling services providers (4) in our database.
Pediatric Physical Medicine & Rehab
See all Pediatric Physical Medicine & Rehab services providers (6) in our database.
For other services related to this condition, browse our Services categories or search our database.
Studies
Current studies of MPS I (ClinicalTrials.gov)
A list of ongoing clinical studies for which patients may be eligible. The list includes registered studies that are closed
and may have links to their published outcomes.
MPS I Registry
An ongoing, observational database that tracks natural history and outcomes of patients with MPS I. The Registry was initiated
worldwide in April 2003 as an international observational program sponsored by BioMarin/Genzyme LLC and administered by Genzyme
Corporation. Registration is voluntary, free, and confidential.