Early Diagnosis and Results of Enzyme Replacement Therapy in the Patient with Mucopolysaccharidosis Type VI: Clinical Case

Background. Mucopolysaccharidosis type VI (MPS VI, Maroteaux–Lamy syndrome) is rare autosomal-recessive multisystem disease, one of the group of lysosomal storage diseases. The MPS VI pathogenesis is determined by arylsulfatase B enzyme deficiency caused by mutations in the ARSB gene. There are only few published clinical examples of this disease that covers the results of early enzyme replacement therapy (ERT) onset.Clinical case description. The child was suspected to have lysosomal storage disease at the age of 1.5 months, it was based on microscopic analysis of blood smears: Alder abnormality was revealed (granulations and red-violet inclusions in neutrophils, monocytes, lymphocytes cytoplasm). The diagnosis was confirmed at the age of 3 months: increased glycosaminoglycans (GAGs) concentration in the urine, arylsulfatase B activity decrease in dried blood spots, and pathogenic variant c.943C>T (p. R315X) in the ARSB gene in homozygous state were revealed. ERT with galsulfase was started at the age of 7 months. There was decrease in excretion of GAGs in urine to normal level after 9 and 15 months of therapy. Normal growth and body proportions for the patient’s age were determined 3 years after continuous ERT. However, there was progression of multiple dysostosis and joint stiffness, as well as eyes lesion.Conclusion. Early ERT onset cannot completely stop MPS VI progression but it allows to reduce the severity of several symptoms and improves patient’s quality of life.

Mucopolysaccharidosis Type VI, an Updated Overview of the Disease

Mucopolysaccharidosis type VI, or Maroteaux–Lamy syndrome, is a rare, autosomal recessive genetic disease, mainly affecting the pediatric age group. The disease is due to pathogenic variants of the ARSB gene, coding for the lysosomal hydrolase N-acetylgalactosamine 4-sulfatase (arylsulfatase B, ASB). The enzyme deficit causes a pathological accumulation of the undegraded glycosaminoglycans dermatan-sulphate and chondroitin-sulphate, natural substrates of ASB activity. Intracellular and extracellular deposits progressively take to a pathological scenario, often severe, involving most organ-systems and generally starting from the osteoarticular apparatus. Neurocognitive and behavioral abilities, commonly described as maintained, have been actually investigated by few studies. The disease, first described in 1963, has a reported prevalence between 0.36 and 1.3 per 100,000 live births across the continents. With this paper, we wish to contribute an updated overview of the disease from the clinical, diagnostic, and therapeutic sides. The numerous in vitro and in vivo preclinical studies conducted in the last 10–15 years to dissect the disease pathogenesis, the efficacy of the available therapeutic treatment (enzyme replacement therapy), as well as new therapies under study are here described. This review also highlights the need to identify new disease biomarkers, potentially speeding up the diagnostic process and the monitoring of therapeutic efficacy.

Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome): defining and measuring functional impacts in pediatric patients

Background Research about pediatric patients’ perspective on mucopolysaccharidosis type VI (MPS VI) and its impact on daily life is limited. We aimed to identify the disease concepts of interest that most impact function and day-to-day life of pediatric patients with MPS VI, and to consider clinical outcome assessments (COAs) that may potentially measure meaningful improvements in these concepts. Methods Potential focus group participants were identified by the National MPS Society (USA) and invited to participate if they self-reported a clinician-provided diagnosis of MPS VI and were 4 to 18 years, receiving enzyme replacement therapy (ERT), and available to attend a 1-day focus group with their caregiver in Dallas, TX, USA. The focus group consisted of a series of polling and open-ended concept elicitation questions and a cognitive debriefing session. The discussion was audio recorded, transcribed verbatim, and analyzed to identify disease concepts of interest and functional impacts most relevant to participants. Results Overall, caregivers (n = 9) and patients with MPS VI (n = 9) endorsed that although their children/they receive ERT, residual symptoms exist and impact health-related quality of life. The key disease concepts of interest identified were impaired mobility, upper extremity and fine motor deficits, pain, and fatigue. Pain was unanimously reported by all patients across many areas of the body and impacted daily activity. Key disease concepts were mapped to a selection of pediatric COAs including generic measures such as PROMIS®, PODCI, CHAQ, and PedsQL™. Caregivers endorsed the relevance of PODCI and PROMIS Upper Extremity, Mobility, and Pain items and all patients completed the NIH Toolbox Pegboard Dexterity Test. Additional COAs that aligned with the disease concepts included range of motion, the 2- and 6-min walk tests, timed stair climbs, Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition, grip strength, pain visual analog scale, and the Faces Pain Scale-Revised. Conclusion An MPS VI focus group of pediatric patients and their caregivers identified impaired mobility, upper extremity and fine motor deficits, pain, and fatigue as key disease concepts of interest. These disease concepts were mapped to existing pediatric COAs, which were provided to the group for endorsement of their relevance.

Compound heterozygous missense mutations in a Chinese mucopolysaccharidosis type VI patient: a case report

Background Mucopolysaccharidosis type VI (MPS VI) is a rare autosomal recessive inherited disease caused by mutations in the arylsulfatase B (ARSB) gene. MPS VI is a multisystemic disease resulting from a deficiency in arylsulfatase B causing an accumulation of glycosaminoglycans in the tissues and organs of the body. In this report, we present the case of a 16-year-old Chinese male who presented with vision loss caused by corneal opacity. MPS VI was confirmed by genetic diagnosis. Case presentation A 16-year-old Chinese male presented with a one-year history of binocular vision loss. The best-corrected visual acuity was 0.25 in the right eye and 0.5 in the left eye. Although slit-lamp examination revealed corneal opacification in both eyes, the ocular examinations of his parents were normal. At the same time, the patient presented with kyphotic deformity, short stature, joint and skeletal malformation, thick lips, long fingers, and coarse facial features. Genetic assessments revealed that ARSB was the causative gene. Compound heterozygous missense mutations were found in the ARSB gene, namely c.1325G > A (p. Thr442Met) (M1) and c.1197G > C (p. Phe399Leu) (M2). Genetic diagnosis confirmed that the patient had MPS VI. Conclusions This paper reports a case of MPS VI confirmed by genetic diagnosis. MPS VI is a multisystem metabolic disease, with corneal opacity as a concomitant ocular symptom. As it is difficult for ophthalmologists to definitively diagnose MPS VI, genetic testing is useful for disease confirmation.

Gasser cell: A biomarker of response to enzyme replacement therapy in patients with mucopolysaccharidosis type VI

The mucopolysaccharidosis (MPS) type VI is a rare lysosomal storage disease presenting leukocyte inclusions (Alder-Reilly anomaly) and lymphocytes with metachromatic inclusion surrounded by clear spaces, Gasser cells. Currently, an enzyme replacement therapy (ERT) with galsulfase is used to treat MPS type VI. This study evaluated 14 patients with MPS type VI performed cell counts Gasser before and after six months from the beginning of ERT. It was observed an average of 12.7% cells per patient, and after six months was found complete cell Gasser disappearance, proving to be an effective biomarker of response to ERT.

Knee and ankle disorders during functional gait in mucopolysaccharidosis type VI

ABSTRACT To evaluate knee and ankle disorders during functional gait assessment in individuals with Mucopolysaccharidosis type VI (MPS VI). 19 subjects were included in this cross-sectional study and allocated in three groups according to age: Children Group (n=11); Adolescent Group (n=4); and Adult Group (n=4). Subphases of one gait cycle were analyzed: Initial contact; Medium support, and Pre-Balance. All volunteers with MPS VI presented greater knee and ankle flexion angles, in all gait subphases, when compared to the normal values defined by literature (p<0.05). Initial contact subphase: knee flexion angle ranging from 8.5º to 15º; Ankle = Child Group −23.73º ± 8.53º; Adolescent Group = −25º ± 11.22º; Adult Group = −27.75º ± 3.3º. Medium support subphase: Knee = Child Group 19.64º ± 10.47º; Adolescent Group 16.75º ± 10.34º; Adult Group = 21.25º ± 12.84º. Ankle = Child Group −18.82º ± 8.91º ± 8.53º; Adolescent Group = −16.5º ± 9.33º; Adult Group = −22.25º ± 4.19º. Pre-Balance subphase: Knee = Child Group 22.72º ± 13.49º; Adolescent Group 21.25º ± 7.97º; Adult Group = 27º ± 16.27º. Ankle = Child Group -15º ± 9.76º; Adolescent Group = −15.75º ± 5.31º; Adult Group = −14.75º ± 3.86º. In this study, MPS VI individuals presented hyperflexion of knee and ankle as the main joint disorders during functional gait, regardless of age.

Step-up approach for surgical treatment of the spinal canal stenosis in a patient with mucopolysaccharidosis type VI (Maroto–Lami syndrome)

The article presents a clinical case of step-up surgical treatment of spinal canal stenosis at the craniovertebral and thoracolumbar level in a patient with mucopolysaccharidosis (MPS) type VI. The treatment method gives an opportunity to achieve a satisfactory result at the background of severe metabolic disease.