Diagnosis and Misdiagnosis of MPS I

Common Misdiagnosis

Those working outside of specialist treatment centres come across MPS I infrequently, therefore the index of suspicion is low.^1,2 Moreover, due to its variable time of onset, severity and phenotype, MPS I is frequently misdiagnosed and under-diagnosed, which leads to many referrals between specialities.² MPS I patients see an average of 5 specialists and wait for approximately 3 years before receiving an accurate diagnosis.²

With some symptoms more easily recognised by particular specialists, collaboration amongst specialties can help to connect the different symptoms and hasten the diagnosis.^1,

Patients with MPS I may share symptoms with many other, often more common diseases.⁴ Paediatricians are in a good position to recognise the red flags of MPS I as they are able to review the medical history of patients who make repeat visits for common childhood complaints.⁵

Common Misdiagnosis of MPS I

Adapted from Hendriksz c 2011¹

If you suspect MPS I, don’t wait – diagnostic testing should be done without delay.¹
Minimise time-to-treatment to potentially slow or prevent development of irreversible conditions that profoundly affect quality of life.³

Diagnosis

Clinician/Metabolic specialist

Diagnosis is made by urinary glycosaminoglycan (uGAG) analysis and confirmed by a molecular genetic test.

Treatment

MPS I treatment

Optimal care involves both support and disease-specific treatment and regular follow up with a multidisciplinary team experienced in the management of MPS. Disease specific therapies include enzyme replacement and haemotopoietic stem cell transplantation.

Adapted from Muenzer et al 2009.³

All patients with suspected MPS should undergo a urinary glycosaminoglycan (uGAG) analysis.^1,6
If the test shows abnormally high levels of GAGs, the patient should be referred to a metabolic specialist for a definitive diagnosis of MPS I.^1,6
Referral to a geneticist for molecular testing identifies mutations and abnormalities in gene coding for the enzyme. Molecular testing is primarily used to confirm the diagnosis of MPS type.⁶
MPS I should be managed by a multidisciplinary team with comprehensive follow up.^1,7

Surgical Connection

MPS I is often difficult to diagnose because of the nonspecific nature of its early symptoms.⁸ Additionally, children with MPS I have a high number of surgeries that are common in childhood, with most having several apparently unrelated operations in early childhood before they receive a diagnosis.⁹

Hernia Repair

Inguinal operations are often performed in older children with MPS I (over the age of 1) compared with the general population (under 1 year of age).⁹ They are usually associated with increased intra-abdominal pressure, hepatosplenomegaly, and weakened muscle and connective tissue, which frequently occur in early MPS I.⁹

Orthopaedic Conditions

Many children with MPS I have skeletal deformities that require evaluation and surgery.^3,7 Among the most common are: spinal deformities, spinal cord compression, joint stiffness, joint contractures, arthropathy, hip dysplasia, knock-knees, claw deformity, carpal tunnel syndrome, and trigger digits.^3,7

Ear, Nose and Throat procedures

Myringotomies, adenoidectomy, and tonsillectomy are the most common surgeries in all children.⁹ Around a third of children with MPS I require these procedures, which tend to occur at an earlier age (around 3 years) compared with the general population (around 7 years).⁹

Carpel Tunnel Syndrome

MPS is one of the most common causes of carpal tunnel syndrome in children and adolescents.^7,9 Carpal tunnel syndrome is one of the top five surgeries in MPS I, being particularly frequent in attenuated forms.⁹

Suspect

• Don’t wait to piece together MPS I. If you see signs and symptoms indicative of MPS I, request a urinary GAG analysis.

Test

• A simple uGAG test is the first step in diagnosing MPS I.⁶ Most patients with the disease will show increased urinary secretion of GAGs (note, this assay is not 100% sensitive).^6,7

Refer

• If the uGAG test result shows abnormally high levels of GAGs, or a uGAG test is not available but signs and symptoms indicate MPS I, the patient should be referred to a metabolic specialist at a specialist treatment centre for a definitive diagnosis.^1,7