Mucopolysaccharidosis Type IVA Research Articles

Phenotype-Genotype Correlation in Morquio A Syndrome: Protocol for a Meta-Analysis.

Mucopolysaccharidosis type IVA (MPS IVA), also known as Morquio A syndrome, is a rare lysosomal storage disease characterized by autosomal recessive inheritance of mutations in the N-acetylgalactosamine-6-sulfatase (GALNS) gene. This leads to a deficiency of the GALNS enzyme, causing the accumulation of glycosaminoglycans in tissues. Morquio A syndrome primarily affects the skeletal system and joints but can also impact various organs, resulting in symptoms such as hearing and vision loss, respiratory issues, spinal cord compression, heart diseases, and hepatomegaly. The genotype-phenotype relationship is diverse, with studies highlighting variants associated with classic, nonclassic, or intermediate phenotypes. Understanding these genetic factors is crucial for predicting disease prognosis and tailoring effective treatment strategies for individuals with Morquio A syndrome. The aim of this meta-analysis is to comprehend the relationship between the severity of the phenotype and the genotype of patients with MPS IVA, considering factors such as the type of variant and its location in the different domains of the protein. This meta-analysis will include articles featuring participants of all genders and age groups who have a molecular diagnosis of MPS IVA and a description of the phenotype. Literature published in English, Spanish, and Portuguese will be considered. Exclusion criteria will encompass studies lacking full-text availability and those involving patients with an MPS IVA diagnosis but without phenotype information. The databases to be searched include PubMed, MEDLINE, ScienceDirect, and Scopus. The screening of literature, paper selection, and data extraction will involve 2 independent reviewers, who will conduct the process blindly. In the event of disagreements between the 2 reviewers at any stage, resolution will be sought through discussion or with the involvement of an additional reviewer. The final selection of manuscripts will be based on consensus. The results of the review will be presented using descriptive statistics, and the information will be organized in either diagrammatic or tabular formats, following the guidelines provided by the Joanna Briggs Institute. Genotype-phenotype relationships will be analyzed using IBM SPSS Statistics, using chi-square tests, Fisher exact tests, and regression analysis to interpret the data. A literature search conducted in January 2024 produced 760 results. The review is expected to be completed by the end of 2024. This meta-analysis will gather and analyze information on the phenotype-genotype relationship in patients diagnosed with MPS IVA. The data collection and resulting analyses will make a substantial contribution to understanding the underlying mechanism of the disease, enabling the prediction of the syndrome's progression and severity. DERR1-10.2196/56649.

Adeno-Associated Virus Gene Transfer Ameliorates Progression of Skeletal Lesions in Mucopolysaccharidosis IVA Mice.

Mucopolysaccharidosis type IVA (MPS IVA) is an autosomal congenital metabolic lysosomal disease caused by a deficiency of the N-acetyl-galactosamine-6-sulfate sulfatase (GALNS) gene, leading to severe skeletal dysplasia. The available therapeutics for patients with MPS IVA, enzyme replacement therapy and hematopoietic stem cell transplantation, revealed limitations in the impact of skeletal lesions. Our previous study, a significant leap forward in MPS IVA research, showed that liver-targeted adeno-associated virus (AAV) gene transfer of human GALNS (hGALNS) restored GALNS enzymatic activity in blood and multiple tissues and partially improved the aberrant accumulation of storage materials. This promising approach was further validated in our current study, where we delivered AAV8 vectors expressing hGALNS, under the control of a liver-specific or ubiquitous promoter, into MPS IVA murine disease models. The results were highly encouraging, with both AAV8 vectors leading to supraphysiological enzymatic activity in plasma and improved cytoplasmic vacuolization of chondrocytes in bone lesions of MPS IVA mice. Notably, the ubiquitous promoter constructs, a potential game-changer, resulted in significantly greater enzyme activity levels in bone and improved pathological findings of cartilage lesions in these mice than in a liver-specific one during the 12-week monitoring period, reinforcing the positive outcomes of our research in MPS IVA treatment.

Implementation of newborn screening for mucopolysaccharidosis type IVA and long-term monitoring in Taiwan

PurposeMucopolysaccharidosis IVA (MPS IVA) is a rare lysosomal storage disorder arising from a deficiency in N-acetylgalactosamine-6-sulfatase. MethodsFrom September 2019 to October 2023, a total of 264,843 Taiwanese newborns underwent screening for MPS IVA using dried blood spots and tandem mass spectrometry. ResultsAmong the 95 referred infants, 9 (9%) were confirmed to have MPS IVA (group 1), 18 (19%) were highly suspected to have MPS IVA (group 2), 61 (64%) were identified as heterozygotes of MPS IVA (group 3), and 7 (7%) were determined not to have MPS IVA (group 4). A total of 34 different GALNS (HGNC:4122) gene variants were identified through our MPS IVA newborn screening program. The most prevalent variant was c.857C>T p.(Thr286Met), found in 33 cases (29%), followed by c.953T>G p.(Met318Arg) in 22 cases (19%). Intravenous enzyme replacement therapy was initiated in 5 patients at ages ranging from 0.3 to 1.7 years. The estimated incidence of MPS IVA in this screening program was 3.4 per 100,000 live births. ConclusionBecause of the progressive nature of MPS IVA, an early diagnosis facilitated by newborn screening and prompt initiation of enzyme replacement therapy before irreversible organ damage occurs may result in improved clinical outcomes.

Adeno-associated virus-based gene therapy delivering combinations of two growth-associated genes to MPS IVA mice

Mucopolysaccharidosis type IVA (MPS IVA) is caused by a deficiency of the N-acetylgalactosamine-6-sulfate sulfatase (GALNS) enzyme responsible for the degradation of specific glycosaminoglycans (GAGs). The progressive accumulation of GAGs leads to various skeletal abnormalities (short stature, hypoplasia, tracheal obstruction) and several symptoms in other organs. To date, no treatment is effective for patients with bone abnormalities. To improve bone pathology, we propose a novel combination treatment with the AAV vectors expressing GALNS enzyme and a C-type natriuretic peptide (CNP; NPPC gene) as a growth-promoting agent for MPS IVA. In this study, an MPS IVA mouse model was treated with an AAV vector expressing GALNS combined with another AAV vector expressing NPPC gene, followed for 12 weeks. After the combination therapy, bone growth in mice was induced with increased enzyme activity in tissues (bone, liver, heart, lung) and plasma. Moreover, there were significant changes in bone morphology in CNP-treated mice with increased CNP activity in plasma. Delivering combinations of CNP and GALNS gene therapies enhanced bone growth in MPS IVA mice more than in GALNS gene therapy alone. Enzyme expression therapy alone fails to reach the bone growth region; our results indicate that combining it with CNP offers a potential alternative.

Morquio A Syndrome: Identification of Differential Patterns of Molecular Pathway Interactions in Bone Lesions.

Mucopolysaccharidosis type IVA (MPS IVA; Morquio A syndrome) is a rare autosomal recessive lysosomal storage disease (LSD) caused by deficiency of a hydrolase enzyme, N-acetylgalactosamine-6-sulfate sulfatase, and characterized clinically by mainly musculoskeletal manifestations. The mechanisms underlying bone involvement in humans are typically explored using invasive techniques such as bone biopsy, which complicates analysis in humans. We compared bone proteomes using DDA and SWATH-MS in wild-type and MPS IVA knockout mice (UNT) to obtain mechanistic information about the disease. Our findings reveal over 1000 dysregulated proteins in knockout mice, including those implicated in oxidative phosphorylation, oxidative stress (reactive oxygen species), DNA damage, and iron transport, and suggest that lactate dehydrogenase may constitute a useful prognostic and follow-up biomarker. Identifying biomarkers that reflect MPS IVA clinical course, severity, and progression have important implications for disease management.

Typical presentation of mucopolysaccharidosis type IVA: a case report

Mucopolysaccharidosis (MPS) IVA, or Morquio syndrome, is a rare lysosomal storage disorder characterized by skeletal dysplasia. It is caused due to deficiency in the enzyme N-acetylgalactosamine-6-sulfatase (GALNS), which results from an autosomal recessive mutation in the GALNS gene. The frequency of this mutation is equivalent in men and women. Here in, we present the case of Morquio syndrome, in a male child of twin gestation with poor antenatal and natal history. The peculiar presentations are those of skeletal deformities, coarse facial features, recurrent respiratory tract infections, and a history of NICU admission for meconium aspiration syndrome. This case is unique because, despite a negative family and prenatal history, and one of the twins being unaffected which adds to its appeal. Later, on biochemical and radiological investigations, he was diagnosed with mucopolysaccharidoses IVA and ultimately managed him supportively.

Newborn screening program for mucopolysaccharidosis type IVA and long-term follow-up of the screen-positive subjects in Taiwan

Newborn screening program for mucopolysaccharidosis type IVA and long-term follow-up of the screen-positive subjects in Taiwan

Integrated Management of an Adult Patient with Mucopolysaccharidosis type IVA: A Case Report with a Six-Year Follow-up.

Mucopolysaccharidosis type IVA (MPS-IVA) is a genetic, rare, and degenerative spondylo-epiphyso-metaphyseal dysplasia characterized by extra-skeletal and skeletal manifestations. The latter impacts on MPS-IVA patient daily activities, and enzyme replacement therapy has a poor efficacy in improving skeletal involvement.The proposed integrated management with enzyme replacement therapy, zoledronic acid, cholecalciferol and bone diet improve both bone mineral density and the prognosis quoad valetudinem of our MPS-IVA patient.

Genotype and Phenotype Characterization of Patients with Mucopolysaccharidosis IV-A in Chile

Introduction: Morquio syndrome or mucopolysaccharidosis type IV-A (MPS IV-A) is an autosomal recessive disease caused by biallelic variants in the GALNS gene, encoding the lysosomal enzyme GalN6S, responsible for glycosaminoglycan keratan sulfate and chondroitin-6-sulfate degradation. Studies have shown that the degree of evolutionary and chemical divergence of missense variants in GalN6S when compared to ancestral amino acids is associated with the severity of the syndrome, suggesting a genotype-phenotype correlation. There is little information on Latin American patients with MPS IV-A that replicate these findings. This study aimed to characterize the phenotype and genotype from patients with MPS IV-A, who are under Enzyme Replacement Therapy at the Children’s Neuropsychiatry Service of the Hospital Clínico San Borja Arriarán, Santiago, Chile, and to determine if there is any association between genotype and phenotype with those findings. Methods: Information was collected from medical charts, all patients went through a GalN6S enzymatic activity measurement in leukocytes from peripheral blood, and the GALNS gene was sequenced for all cases. Results: 12 patients with MPS IV-A were recruited, all patients presented multisystem involvement, mostly skeletal, and 75% of cases underwent surgical interventions, and cervical arthrodesis was the most frequent procedure. In regards of the genotype, the two most frequent variants were c.319+2T>C (n = 10, 41.66%) and p.(Arg386Cys) (n = 8, 33.33%), the first one was previously described in 2018 in a patient from Chile [Bochernitsan et al., 2018]. Conclusion: This is the first time that a genotype-phenotype correlation has been studied by analyzing the variants effect on the molecular structure of human GalN6S and the evolutionary conservation degree of affected residues in a cohort of patients in Chile. Albeit our work could not find statistically significant associations, we may infer that the evolutionary conservations of affected amino acids and the effect of variants on enzyme structure may play a main role. Further analyzes should consider a meta-analysis of published cases with genotype data and larger samples and include other variables that could provide more information. Finally, our data strongly suggest that variant c.319+2T>C could have a founder effect in Chilean patients with MPS IV-A.

Endoscopic and Image Analysis of the Airway in Patients with Mucopolysaccharidosis Type IVA.

Mucopolysaccharidosis (MPS) is a hereditary disorder arising from lysosomal enzymes deficiency, with glycosaminoglycans (GAGs) storage in connective tissues and bones, which may compromise the airway. This retrospective study evaluated patients with MPS type IVA with airway obstruction detected via endoscopy and imaging modalities and the effects of surgical interventions based on symptoms. The data of 15 MPS type IVA patients (10 males, 5 females, mean age 17.8 years) were reviewed in detail. Fiberoptic bronchoscopy (FB) was used to distinguish adenotonsillar hypertrophy, prolapsed soft palate, secondary laryngomalacia, vocal cord granulation, cricoid thickness, tracheal stenosis, shape of tracheal lumen, nodular deposition, tracheal kinking, tracheomalacia with rigid tracheal wall, and bronchial collapse. Computed tomography (CT) helped to measure the deformed sternal angle, the cross-sectional area of the trachea, and its narrowest/widest ratio (NW ratio), while angiography with 3D reconstruction delineated tracheal torsion, kinking, or framework damage and external vascular compression of the trachea. The NW ratio correlated negatively with age (p < 0.01), showing that airway obstruction progressed gradually. Various types of airway surgery were performed to correct the respiratory dysfunction. MPS type IVA challenges the management of multifactorial airway obstruction. Preoperative airway evaluation with both FB and CT is strongly suggested to assess both intraluminal and extraluminal factors causing airway obstruction.

Pharmacological chaperones as an alternative to increase GALNS activity in mucopolysaccharidosis type IVA

Pharmacological chaperones as an alternative to increase GALNS activity in mucopolysaccharidosis type IVA

Clinical Characteristics of a Patient with Mucopolysaccharidosis Type IVA (Morquio Syndrome)

Mucopolysaccharidosis (MPS) type IVA (Morquio syndrome) is a hereditary lysosomal storage disease caused by deficiency of N-acetylglucosamine-6-sulfate sulfatase. This enzyme deficiency leads to specific glycosaminoglycans (keratan sulfate and chondroitin-6sulfate) accumulation mainly in the bone and cartilage tissues, as well as in the cardiovascular, respiratory systems, and visual systems. Patients with MPS IVA look healthy at birth, however, they develop typical spine deformities (kyphoscoliosis), pectus carinatum, wrists hypermobility with decreased muscle strength and loss of fine motor skills, valgus deformation of lower limbs during the first years of life. Pathological changes in cardiovascular and respiratory systems, visual and acoustic analyzers can be revealed. Early diagnosis of the disease is crucial for timely initiation of enzyme replacement therapy. Thus, low incidence of the disease and its heterogeneous clinical picture complicates diagnosis. Consequently, patients with MAS IVA often become severely disabled as early as adolescence. Patients with severe form and without treatment die before the age of 30 due to complications of respiratory system diseases, valvular heart apparatus involvement, and cervical myelopathy.

Genotypes and phenotypes of Sri Lankan Patients with Mucopolysaccharidosis type IVA

Mucopolysaccharidosis type IVA is a rare autosomal recessive lysosomal storage disorder occurring worldwide in all ethnic groups. It is caused by biallelic variants in the GALNS gene (OMIM 612222). We report five cases of mucopolysaccharidosis type IVA with short stature and severe skeletal dysplasia. An optimized diagnostic strategy that combined enzymatic testing and genetic screening was applied. All the tested urine samples showed increased urinary glycosaminoglycan / creatinine ratios. In all five cases, the enzyme activity of galactosamine-6-sulfate sulfatase was pathologically decreased. Gene-targeted sequencing revealed a previously unreported homozygous c.139-12T&gt;C variant of the GALNS gene in one patient and three previously reported missense variants in four patients; c.253T&gt;C (p.Cys85Arg), c.626C&gt;T (p.Ala209Val) and c.878C&gt;T (p.Ser293Leu). Genetic studies not only confirm the diagnosis of mucopolysaccharidosis IVA, but also enable predicting the prognosis and facilitate genetic counseling. Enzyme replacement therapy is not available in Sri Lanka to date. However, the quality of life in these patients can be improved by a multidisciplinary approach.

Rapid Targeted Sequencing Using Dried Blood Spot Samples for Patients With Suspected Actionable Genetic Diseases.

New genome sequencing technologies with enhanced diagnostic efficiency have emerged. Rapid and timely diagnosis of treatable rare genetic diseases can alter their medical management and clinical course. However, multiple factors, including ethical issues, must be considered. We designed a targeted sequencing platform to avoid ethical issues and reduce the turnaround time. We designed an automated sequencing platform using dried blood spot samples and a NEOseq_ACTION panel comprising 254 genes associated with Mendelian diseases having curable or manageable treatment options. Retrospective validation was performed using data from 24 genetically and biochemically confirmed patients. Prospective validation was performed using data from 111 patients with suspected actionable genetic diseases. In prospective clinical validation, 13.5% patients presented with medically actionable diseases, including short- or medium-chain acyl-CoA dehydrogenase deficiencies (N=6), hyperphenylalaninemia (N=2), mucopolysaccharidosis type IVA (N=1), alpha thalassemia (N=1), 3-methylcrotonyl-CoA carboxylase 2 deficiency (N=1), propionic acidemia (N=1), glycogen storage disease, type IX(a) (N=1), congenital myasthenic syndrome (N=1), and citrullinemia, type II (N=1). Using the automated analytic pipeline, the turnaround time from blood collection to result reporting was <4 days. This pilot study evaluated the possibility of rapid and timely diagnosis of treatable rare genetic diseases using a panel designed by a multidisciplinary team. The automated analytic pipeline maximized the clinical utility of rapid targeted sequencing for medically actionable genes, providing a strategy for appropriate and timely treatment of rare genetic diseases.

Exome Sequencing Identifies a Biallelic GALNS Variant (p.Asp233Asn) Causing Mucopolysaccharidosis Type IVA in a Pakistani Consanguineous Family.

Mucopolysaccharidoses (MPS) type IVA is a lysosomal storage disease that mainly affects the skeletal system and is caused by a deficiency of the enzyme N-acetylgalactosamine-6-sulfatase (GALNS). The condition can mistakenly be diagnosed as a primary skeletal dysplasia such as spondylo-epiphyseal dysplasia, which shares many similar phenotypic features. Here, we utilised whole exome sequencing to make the diagnosis of MPS IVA in a resource poor country. We report for the first time the identification of a biallelic GALNS missense variant (c.697G>A, p.Asp233Asn) in the Pakistani population and highlight the potential contribution that academic institutions can make in rare disease diagnosis in the absence of a developed clinical genetic service.

Efficacy of Intravenous Elosulfase Alfa for Mucopolysaccharidosis Type IVA: A Systematic Review and Meta-Analysis.

Mucopolysaccharidosis type IVA (MPS IVA or Morquio A), a lysosomal storage disease with an autosomal recessive inherited pattern, is induced by GALNS gene mutations causing deficiency in N-acetylgalactosamine-6-sulfatase activity (GALNS; EC 3.1.6.4). Currently, intravenous (IV) enzyme replacement therapy (ERT) with elosulfase alfa is employed for treating MPS IVA patients. A systematic literature review was conducted to evaluate the efficacy and safety of IV elosulfase alfa for MPS IVA by searching the National Center for Biotechnology Information, U.S. National Library of Medicine National Institutes of Health (PubMed), Excerpta Medica dataBASE, and Cochrane Library databases, limited to clinical trials. Four cohort studies and two randomized controlled trials, with a total of 550 participants (327 on ERT treatment versus 223 on placebo treatment), satisfied the inclusion criteria. Pooled analysis of proportions and confidence intervals were also utilized to systematically review clinical cohort studies and trials. Per the pooled proportions analysis, the difference in means of urinary keratan sulfate (uKS), 6-min walk test, 3-min stair climb test, self-care MPS-Health Assessment Questionnaire, caregiver assistance and mobility, forced vital capacity, the first second of forced expiration, and maximal voluntary ventilation between the ERT and placebo treatment groups were −0.260, −0.102, −0.182, −0.360, −0.408, −0.587, −0.293, −0.311, and −0.213, respectively. Based on the currently available data, our meta-analysis showed that there is uKS, physical performance, quality of life, and respiratory function improvements with ERT in MPS IVA patients. It is optimal to start ERT after diagnosis.

Flaxseed extract reduces tissue accumulation and enhances urinary excretion of chondroitin sulphate in the rat: a possible new path in substrate reduction therapy for mucopolysaccharidosis

Context Chondroitin 6 sulphate (C6S) is a glycosaminoglycan (GAG) whose accumulation is notable in mucopolysaccharidosis type IVA and VII. Flaxseed, Linum usitatissimum L. (Linaceae) (FS), is reported to have comparable properties to those of soybean, a source of genistein, a potential new treatment for MPSs. Objective We assess the effect of total ethanol flaxseed extract (EFSE) in an animal model of C6S accumulation. Materials and methods The study was performed in adult male Wistar rats (n = 24) for 15 successive days. The animals were divided into four groups: (1) control injected with physiological saline buffer, (2) intoxicated rats injected intraperitoneally with C6S, (3) intoxicated with C6S and treated with EFSE, and (4) treated with EFSE. All groups were subjected to histopathological and biochemical studies. The antioxidant and phytochemical properties of EFSE were examined. Results Dry EFSE contains total phenols (6.28 mg EAG/g), condensed tannins (2.98 mg ECAT/g) and flavonoids (0.44 mg ECAT/g) with high antioxidant potential [RPE (IC50 = 8.37 ± 0.176), DPPH (IC50 = 12.79 ± 0.273)]. The LD50 is higher than 5000 mg/kg. The histopathological examination showed an accumulation of C6S in the C6S intoxicated group, which disappeared in the C6S-EFSE treated group. GAGs assays showed an increased excretion in the C6S intoxicated group and increased excretion of 14% in the C6S-EFSE group compared to the C6S group. Discussion and conclusions EFSE showed significant potential for chelation. Its use for the treatment of GAG accumulation could be suggested and generalized to a larger study population.

Mucopolysaccharidosis Type IVA: Extracellular Matrix Biomarkers in Cardiovascular Disease.

Cardiovascular disease (CVD) in Mucopolysaccharidosis Type IVA (Morquio A), signified by valvular disease and cardiac hypertrophy, is the second leading cause of death and remains untouched by current therapies. Enzyme replacement therapy (ERT) is the gold-standard treatment for MPS disorders including Morquio A. Early administration of ERT improves outcomes of patients from childhood to adulthood while posing new challenges including prognosis of CVD and ERT’s negligible effect on cardiovascular health. Thus, having accurate biomarkers for CVD could be critical. Here we show that cathepsin S (CTSS) and elastin (ELN) can be used as biomarkers of extracellular matrix remodeling in Morquio A disease. We found in a cohort of 54 treatment naïve Morquio A patients and 74 normal controls that CTSS shows promising attributes as a biomarker in young Morquio A children. On the other hand, ELN shows promising attributes as a biomarker in adolescent and adult Morquio A. Plasma/urine keratan sulfate (KS), and urinary glycosaminoglycan (GAG) levels were significantly higher in Morquio A patients (p < 0.001) which decreased with age of patients. CTSS levels did not correlate with patients’ phenotypic severity but differed significantly between patients (median range 5.45–8.52 ng/mL) and normal controls (median range 9.61–15.9 ng/mL; p < 0.001). We also studied α -2-macroglobulin (A2M), C-reactive protein (CRP), and circulating vascular cell adhesion molecule-1 (sVCAM-1) in a subset of samples to understand the relation between ECM biomarkers and the severity of CVD in Morquio A patients. Our experiments revealed that CRP and sVCAM-1 levels were lower in Morquio A patients compared to normal controls. We also observed a strong inverse correlation between urine/plasma KS and CRP (p = 0.013 and p = 0.022, respectively) in Morquio A patients as well as a moderate correlation between sVCAM-1 and CTSS in Morquio A patients at all ages (p = 0.03). As the first study to date investigating CTSS and ELN levels in Morquio A patients and in the normal population, our results establish a starting point for more elaborate studies in larger populations to understand how CTSS and ELN levels correlate with Morquio A severity.

Clinical characteristics and effects of enzyme replacement therapy with elosulfase alfa in Korean patients with mucopolysaccharidosis type IVA

Mucopolysaccharidosis type IVA (MPS IVA) is a rare autosomal recessive disorder caused by a deficiency in N-acetylgalactosamine-6-sulfatase, which results in skeletal and connective tissue abnormalities, as well as various non-skeletal manifestations. Although enzyme replacement therapy (ERT) is recommended as the first-line treatment, the outcomes of ERT on bone pathology remain controversial. We report clinical characteristics and outcomes of ERT in 9 patients with MPS IVA (6 males and 3 females) from 7 unrelated families. During ERT, results from pulmonary function tests, echocardiography, the 6-min walk test, and the Functional Independence Measure were monitored biannually. Anthropometric data were compared with previously reported growth charts of subjects with MPS IVA.Among the 9 patients (5 severe, and 4 slowly progressive form), 7 patients (5 severe, 2 slowly progressive) commenced ERT at a median age of 3.8 years (range: 0.8–13.7 years) and were treated for a median duration of 1.9 years (range: 1.2–5.7 years). Mean height standard deviation scores using MPS IVA growth charts were + 0.4 (+0.0 in severe phenotypes) at initiation and + 0.7 (+0.2 in severe phenotypes) at the last follow-up. Four patients with severe phenotypes underwent surgery for cervical myelopathy and 1 patient with a slowly progressive phenotype underwent a bilateral pelvic osteotomy for hip pain during ERT. The parameters of pulmonary and heart function, endurance, and Functional Independence Measure scores were maintained or increased after ERT. Overall, ERT was well tolerated without deterioration of cardiorespiratory and functional outcomes during treatment, although skeletal outcomes, including growth, were limited.

Molecular Modeling and Phenotypic Description of a Patient with a Novel Exonic Deletion of GALNS with Resultant Morquio Syndrome with Two Successful Pregnancies

In this report, we describe phenotypic features of a patient with mucopolysaccharidosis type IVA (Morquio syndrome) harboring a novel exon 1 deletion in GALNS with enzymatic confirmation consistent with Morquio syndrome. To our knowledge, this is the first reported case of this variant. Additionally, we protein modelled wild-type GALNS and the pathogenic variant with an exon 1 deletion for comparative analysis using statistical mechanics methods described herein. We demonstrate that, even when the protein is translated, the mutation would affect protein stability and function via homodimer interaction modifications. Lastly, given the patient’s 2 successful pregnancies, data about the management of pregnancies in mucopolysaccharidoses are reviewed, and we discuss the management of pregnancy in patients with Morquio syndrome.