Understanding bias when estimating life expectancy from age at death: a simulation approach applied to Morquio syndrome A

Objective Life expectancy can be estimated accurately from a cohort of individuals born in the same year and followed from birth to death. However, due to the resource-consuming nature of following a cohort prospectively, life expectancy is often assessed based upon retrospective death record reviews. This conventional approach may lead to potentially biased estimates, in particular when estimating life expectancy of rare diseases such as Morquio syndrome A. We investigated the accuracy of life expectancy estimation using death records by simulating the survival of individuals with Morquio syndrome A under four different scenarios. Results When life expectancy was constant during the entire period, using death data did not result in a biased estimate. However, when life expectancy increased over time, as is often expected to be the case in rare diseases, using only death data led to a substantial underestimation of life expectancy. We emphasize that it is therefore crucial to understand how estimates of life expectancy are obtained, to interpret them in an appropriate context, and to assess estimation methods within a sensitivity analysis framework, similar to the simulations performed herein.

Increased Choroidal Thickness in Morquio Syndrome

The purpose of this clinical case report is to describe a case of mucopolysaccharidosis type IVA (MPS IVA), or Morquio syndrome, with increased choroidal thickness in enhanced-depth imaging optical coherence tomography (EDI-OCT) which can represent choroidal deposition of glycosaminoglycans (GAGs). A 21-year-old male with genetically confirmed diagnosis of MPS IVA was examined at our Pediatric Ophthalmology clinic as part of our follow-up protocol for MPS patients. His best-corrected visual acuity was 4/10 in his right eye (OD) and 6/10 in the left eye (OS). Mild diffuse corneal opacification was evident. Intraocular pressure was within normal range. Fundus examination and color fundus photography revealed no abnormalities. EDI-OCT revealed significantly increased choroidal thickness in his right eye and in his left eye, suggesting the presence of choroidal deposition of GAGs, despite absence of retinal or optic disc GAG deposition or other chorioretinal involvement. To our knowledge, this is the first case of MPS IVA described in the literature with suspected choroidal deposition of GAGs. With improved control of systemic features of MPS IVA, life expectancy of these patients has increased, allowing for more ocular manifestations to develop. The parallel development of technology in ophthalmology, such as the EDI-OCT, further contributes to the detection of these unprecedented ocular features in MPSs.

Evaluation of Gait Pattern and Lower Extremity Kinematics of Children with Morquio Syndrome (MPS IV)

Morquio syndrome (mucopolysaccharidosis IV/MPS IV) is a genetic disorder leading to skeletal abnormalities and gait deviations. Research on the gait patterns and lower extremity physical characteristics associated with skeletal dysplasia in children with MPS IV is currently limited. This research aimed to provide baseline gait patterns and lower limb skeletal alignment of children with MPS IV utilizing three-dimensional instrumented gait analysis. This Institutional Review Board-approved retrospective study evaluates the kinematics of the lower extremities of children with MPS IV during gait, comparing them with an age-matched group of typically developing children. Thirty-three children with MPS IV were included (8.6 ± 4.0 years old). Children with MPS IV walk with increased anterior pelvic tilt, knee valgus, knee flexion, external tibial torsion, and reduced walking speed and stride length (p < 0.001). Multiplanar abnormal alignment results in abnormal knee moments (p < 0.001). Limited correlations exist (r = 0.69–0.28) between dynamic three-dimensional measurements of knee varus/valgus and rotational alignment and traditional static two-dimensional measures (physical examination or radiographs) suggesting the possibility of knee instability during gait and the benefits of dynamic assessment.

Automated Assessment of Thoracic-Abdominal Asynchrony in Patients with Morquio Syndrome

Morquio syndrome is a rare disease caused by a disorder in the storage of mucopolysaccharides that affects multiple organs, including musculoskeletal, respiratory, cardiovascular, and digestive systems. Respiratory failure is one of the leading causes of mortality in Morquio patients; thus, respiratory function testing is vital to the management of the disease. An automated respiratory assessment methodology using the pneuRIP device and a machine-learning algorithm was developed. pneuRIP is a noninvasive approach that uses differences between thoracic and abdominal movements (thoracic-abdominal asynchrony) during respiration to assess respiratory status. The technique was evaluated on 17 patients with Morquio (9 females and 8 males) between the ages of 2 and 57 years. The results of the automated technique agreed with the clinical assessment in 16 out of the 17 patients. It was found that the inverse cumulative percentage representation of the time delay between the thorax and abdomen was the most critical variable for accurate evaluation. It was demonstrated that the technique could be successfully used on patients with Morquio who have difficulty breathing with 100% compliance. This technique is highly accurate, portable, noninvasive, and easy to administer, making it suitable for a variety of settings, such as outpatient clinics, at home, and emergency rooms.

Total Hip Arthroplasty in a Patient with Mucopolysaccharidosis Type IVB

Introduction. Morquio syndrome or mucopolysaccharidosis (MPS) type IV is a rare autosomal recessive lysosomal storage disease, characterized by abnormal metabolism of glycosaminoglycans associated with specific skeletal deformities, also known as dysostosis multiplex. Case Presentation. We present the case of a 23-year-old patient with advanced osteonecrosis of the femoral head (ONFH) on both sides due to Morquio syndrome. A diagnosis of mucopolysaccharidosis type IVB was made after extensive genetic profiling. The patient had the condition for a long time. At 7 years old, the patient was treated with bilateral pelvic Salter’s osteotomy. Afterward, the patient was able to walk freely but could never take part in sports. At 22 years old, pain in the hip increased, and magnetic resonance imaging showed a bilateral femur head necrosis. Hence, the patient underwent cementless total hip arthroplasty (THA). Intraoperatively, a periprosthetic fracture occurred. Therefore, revision surgery with internal fixation was performed on the next day. Postoperatively, a weight-bearing restriction of 20 kg on the left leg was imposed for 6 weeks. The patient made a full recovery and was able to move without residual complaints. Annual orthopedic evaluation in patients treated with surgical intervention is recommended. Discussion. Orthopedic challenges for mucopolysaccharidoses and corresponding bone alterations, known as dysostosis multiplex, involving trunk and limbs with typical radiological findings have been well described. The hip is invariably involved, with dysplasia affecting the femoral neck (coxa valga), femoral epiphysis (loss of sphericity, osteonecrosis), and a flared hypoplastic iliac wing. Symptomatic therapy consists, on the one hand, of a surgical procedure and, on the other hand, a variety of supportive measures. However, the management of joint replacement in lysosomal storage diseases has not been well reported. All patients with MPS should be considered at high risk for surgical intervention requiring anesthesia because of airway and cardiac disease manifestations. In the case of a need for THA, we recommend cemented stem fixation because of the overall poor bone quality in patients with Morquio syndrome.