Growth impairment and limited range of joint motion in children should raise suspicion of an attenuated form of mucopolysaccharidosis: expert opinion

Abstract

Growth impairment together with bone and joint involvement is common to most patients with mucopolysaccharidosis (MPS) disorders. The genetic basis for these metabolic disorders involves various enzyme deficiencies responsible for the catabolism of glycosaminoglycans (GAGs). The incomplete degradation and subsequent accumulation of GAGs result in progressive tissue damage throughout the body. Bone ossification is particularly affected, with the consequent onset of dysostosis multiplex which is the underlying cause of short stature. Joint manifestations, whether joint contractures (MPS I, II, VI, VII) or hyperlaxity (MPS IV), affect fine motor skills and quality of life. Subtle decreases in growth velocity can begin as early as 2–4 years of age. Pediatricians are in the front line to recognize or suspect MPS. However, given the rarity of the disorders and variable ages of symptom onset depending on disease severity, recognition and diagnostic delays remain a challenge, especially for the attenuated forms. Prompt diagnosis and treatment can prevent irreversible disease outcomes. Conclusion : We present a diagnostic algorithm based on growth velocity decline and bone and joint involvement designed to help pediatricians recognize early manifestations of attenuated forms of MPS. We illustrate the paper with examples of abnormal growth curves and subtle radiographic nuances. What is Known: • As mucopolysaccharidoses (MPSs) are rare genetic disorders infrequently seen in clinical practice, there can be a lag between symptom onset and diagnosis, especially of attenuated forms of the disease. • This highlights the need for increased disease awareness to recognize early clinical signs and subsequently initiate early treatment to improve outcomes (normal height potential) and possibly prevent or delay the development of irreversible disease manifestations. What is New: • Growth impairment co-presenting with limited range of joint motion and radiographic anomalies in children should raise suspicions of possible attenuated MPS (AMPS). • Experts present a diagnostic algorithm with detailed focus on the decline in growth velocity, delayed puberty and limitation in joint mobility seen in children with AMPS, to shorten time-to-diagnosis and treatment and potentially improve patient outcome.

Mucopolysaccharidosis Type I: A Review of the Natural History and Molecular Pathology

“…Other manifestations in the lower extremities include coxa valga and genu valgum. Joint symptoms, such as joint stiffness and limited range of joint mobility, stem from GAG accumulation and secondary pathogenic cascades in the ligaments and capsule around the joints [88,89].…”

Home treatment of type VI mucopolysaccharidosis (Maroteaux‐Lamy syndrome) an alternative at this time of COVID‐19 pandemic: A case in Peru

“…Abnormal growth is a frequent finding in MPS patients. In particular, in patients with MPS VI, normal growth is evident until 1.5 years of age and is then followed by growth stunting (−2 to −3 SD at 3.5 and 9 years, respectively) 21 . Clinical trials with ERT have shown a slight improvement in growth rate (height), which is not statistically significant when compared to patients who are not on treatment 22 .…”

Clinical and genetic characteristics of concomitant Mucopolysaccharidosis type IVA and neurogenic bladder in children: two case reports and literature review

“…It is a challenge to correctly diagnose MPS IVA, especially in its attenuated form, because of the wide spectrum of clinical characteristics in patients with MPS IVA and because the radiographic findings are similar to those in patients with multiple epiphyseal dysplasia. Experts have presented a diagnostic algorithm based on the decline in growth velocity as well as bone and joint involvement that was designed to help paediatricians identify the early characteristics of the attenuated forms of MPS [ 13 ]. Once MPS is clinically suspected, urinary GAG analysis and enzyme detection are crucial for accurate diagnosis and prognosis of MPS subtypes [ 13 ].…”

“…Experts have presented a diagnostic algorithm based on the decline in growth velocity as well as bone and joint involvement that was designed to help paediatricians identify the early characteristics of the attenuated forms of MPS [ 13 ]. Once MPS is clinically suspected, urinary GAG analysis and enzyme detection are crucial for accurate diagnosis and prognosis of MPS subtypes [ 13 ]. However, the clinical features in patients with mild MPS are atypical, and mutation in other genes can lead to decreased GALNS activity such as multiple sulfatase deficiency, increasing the difficulty of diagnosing this disease [ 14 ].…”