Dens Growth After Surgical Fixation in Children with Morquio-Brailsford Disease.

Mucopolysaccharidosis type IVA is a lysosomal storage disorder caused by a deficiency of the enzyme N-acetyl-galactosamine-6-sulphate sulphatase. Mucopolysaccharidosis type IVA is multisystemic disease with significant spinal involvement and atlantoaxial instability leading to neural compression and significant morbidity. Dens hypoplasia is a common feature of this condition. In this study we demonstrate that after spinal fixation, there is new growth of dens in significant proportion of patients, suggesting atlantoaxial instability as one of the major driving forces of lack of development of dens in this condition.

How did intraoperative neuromonitorization prevent tetraplegia?

PURPOSE: Patients with mucopolysaccharidosis type IVA (MPS IVA) have many risk factors for myelopathy and paresis. These are spinal cord compression, bone stenosis, and soft tissue thickening with ligament laxity, deformity, odontoid hypoplasia, and atlantoaxial instability. Although most patients with MPS IVA appear generally healthy at birth, patients often show skeletal deformities within a few years. Surgical indications are difficult to determine. Historically, many physicians have used prophylactic decompression and fusion in young, asymptomatic MPS IVA patients to prevent cord compression. Although spinal cord decompression is usually required at the craniocervical junction in patients with MPS IVA, decompression may be required at other spinal cord levels as well. There is a risk of developing neurological damage during surgery. The most common causes are ischemia secondary to cardiac output deteriorated in the prone position or due to artery damage, and local trauma due to neck movements or traction while bringing the patient to the prone position. Neurophysiological monitoring is very important during surgery to reduce the risk of neurological damage in spinal cord surgery. In this case report, a case with loss of lower extremity neuromonitorization motor evoked potential (MEP) responses in the early period of surgery without any intervention to the craniocervical junction after prone positioning will be presented.

Manejo anestésico de una gestante con síndrome de Morquio / Anesthetic Management for a pregnant woman with Morquio syndrome Sobre los autores:

Introducción: El síndrome de Morquio es una enfermedad hereditaria autosómica recesiva con distintos grados de afectación al metabolismo de los glúcidos, lo que genera incapacidad para romper los enlaces de las cadenas largas de glucosamiglicanos, esto provoca acumulación de mucopolisacáridos en distintos tejidos del cuerpo humano. Objetivo: Describir el manejo anestésico de una gestante con síndrome de Morquio. Presentación del caso: Gestante primigesta de 30 años de edad, de raza negra, de 103 cm de estatura y 33 Kg de peso. Acude a consulta preoperatoria por presentar embarazo a término, baja talla y se realizó interrupción del embarazo por vía alta. Se procede a la valoración preanestésica donde se recoge antecedentes de enfermedad genética e ingreso previo por presentar cifras elevadas de tensión arterial. La paciente padecía de alergia a la dipirona. Conclusiones: Los pacientes con mucopolisacaridosis tienen una alta incidencia de dificultad para la ventilación y la intubación endotraqueal asociada con insuficiencia cardiopulmonar. La afectación de la columna presenta dificultades adicionales para los anestesiólogos. Cualquier cirugía electiva requiere una evaluación preoperatoria de los factores de riesgo anestesiológicos y la disponibilidad de un espectro de equipos para el manejo de las vías respiratorias. La anestesia debe ser realizada por un equipo con experiencia en el manejo de la vía aérea(AU)

Introduction: Morquio syndrome is an autosomal recessive hereditary disease that affects, to different extents, carbohydrate metabolism, which obstructs the ability to break bonds of long chains of glycosaminoglycans, causing mucopolysaccharides accumulation in different tissues of the human body. Objective: To describe the anesthetic management of a pregnant woman with Morquio syndrome. Case presentation: This is the case of a 30-year-old primigravid pregnant woman, of black skin, 103 cm of height and 33 kg of weight. She came for preoperative consultation because she was pregnant at term and had low body size; the pregnancy was terminated through the abdominal route. A preanesthetic assessment was performed, which permitted to observe a history of genetic disease and previous admission for high blood pressure. The patient was allergic to dipyrone. Conclusions: Among patients with mucopolysaccharidosis, there is a high incidence of difficulty for ventilation and endotracheal intubation associated with cardiopulmonary insufficiency. Spinal involvement represents additional difficulties for anesthesiologists. Any elective surgery requires preoperative assessment of anesthesiologic risk factors and the availability of a spectrum of airway management equipment. Anesthetic managment should be performed by a team experienced in airway management(AU)

Airway Management of the Deformed Trachea Using T-Tube Stents in Patients with Mucopolysaccharidosis Type IVA.

INTRODUCTION: Mucopolysaccharidosis (MPS) type IVA usually results in airway obstruction due to thoracic cage deformity and crowding of intrathoracic structures, causing tracheal compression by the tortuous innominate artery. OBJECTIVES: To offer an alternative and effective method in dealing with the challenged deformity of the airway in patients with MPS type IVA. METHODS: We present 3 patients with MPS type IVA who underwent airway stenting using Montgomery® T-tube stents. Three-dimensional reconstructed computed tomography was essential to design the T-tube and evaluate the anatomical relationship between the innominate artery and the trachea. The Y-shaped Montgomery® Pediatric Safe-T-Tube™ is more suitable for MPS type IVA. Regular follow-ups using fiberoptic bronchoscopy are necessary to evaluate the complications. RESULTS: All 3 patients had good outcomes during the follow-ups until present, despite the complication of granulation formation, which was resolved by revising the limbs of the T-tube. CONCLUSIONS: T-tube stents placed below the vocal cord may restore airway patency and preserve laryngeal function, including respiration, phonation, and swallowing, in patients with MPS type IVA.

Cervical Disorders in Mucopolysaccharidosis IVA-Morquio disease.

Morquio disease or mucopolysaccharidosis type IVA (Online Mendelian Inheritance in Man No. 253000) is a rare autosomal recessive disease classified in the group of metabolism inborn errors. The glycosaminoglycans accumulate in chondrocytes, which disturbs bone growth and leads to skeletal manifestations, such as skeletal dysplasia and a short stature. In addition, the disproportionate growth of the trachea can lead to airway insufficiency. We report the case of a 27-year-old man with dwarfism due to Morquio disease, which had resulted in quadriparesis, hyperreflexia, and dyspnea, requiring a "look up to the sky" compensatory position. Imaging studies of the neck showed tracheal tortuosity, spinal stenosis, myelopathy, and neurogenic arthropathy (Charcot joint). The patient was treated with occipital-cervical-thoracic instrumentation. However, postoperative tracheal correction was required. Considering the wide spectrum of clinical features in those with mucopolysaccharidosis type IVA, individualized multidisciplinary treatment is recommended.

Evaluation of sleep-disordered breathing and its relationship with respiratory parameters in children with mucopolysaccharidosis Type IVA and VI.

The aims of the study were to evaluate the prevalence of sleep-disordered breathing (SDB) by using polysomnography (PSG) in children with MPS IVA and MPS VI who underwent enzyme replacement therapy (ERT) and to analyze the effect on SDB of having upper airway surgery, pulmonary functions, and exercise capacity. A retrospective cross-sectional study was conducted on patients with MPS IVA (n:17) and MPS VI (n:11) aged under 19 years who underwent polysomnography. Descriptive and nonparametric analyses were performed for demographic, PSG, pulmonary function and exercise capacity variables. The frequency of sleep apnea in the study sample was 85.7% (24/28). Four patients (14.3%) had no sleep apnea, 15 (53.6%) had mild, and nine (32.1%) had moderate-to-severe sleep apnea. Two patients (7.1%) had central sleep apnea and 22 had obstructive sleep apnea (OSA) (78.6%). Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were negatively correlated to apnea-hypopnea index (AHI) (r = -0.594, p = .009; r = -0.636, p = .005, respectively). Despite ERT and previous upper airway surgery, the prevalence of OSA was high in patients with MPS IVA-MPS IV, emphasizing the importance of PSG screening for sleep disorders. Pulmonary function tests may be useful for predicting sleep apnea in patients with MPS IVA and MPS VI.

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

BACKGROUND: Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is a rare autosomal recessive lysosomal storage disorder. Up to now, reports on the clinical characteristics of MPS IVA mainly focused on patients with progressive bone dysplasia and multiple organ damage, while the effects of this disorder on neurogenic bladder have not been reported. Therefore, the aim of the present study is to report two cases of nocturnal enuresis finally diagnosed as neurogenic bladder in MPS IVA. CASE PRESENTATION: Both children were characterized by the presence of pectus carinatum, kyphoscoliosis, nocturnal enuresis, urinary incontinence, normal intelligence, and loss of strength in the legs, diagnosed as neurogenic bladder in association with MPS IVA through the analysis of the clinical characteristics, enzyme activity and genetic testing. In addition, the terminator codon mutation c.1567T > G (p.X523E) and a novel missense mutation c.575A > G (p.E192G) were found in the coding region of the GALNS gene of the 1st patient, while the missense mutation c.488C > A (p.P163H) was found in the coding region of the GALNS gene of the 2nd patient. CONCLUSIONS: Neurogenic bladder may occur in patients with MPS IVA after spinal cord injury. It is necessary to screen for the diagnosis of MPS IVA in patients with atypical enuresis and skeletal abnormalities through the analysis of the clinical characteristics, enzyme activity and genetic testing.

Otorhinolaryngological manifestations in 61 patients with mucopolysaccharidosis.

OBJECTIVES: The mucopolysaccharidoses (MPS) are inherited lysosomal storage disorders with multisystemic and highly variable clinical manifestation. ENT symptoms are common and early signs of MPS. The most common ENT diagnoses are chronic/recurrent rhinosinusitis, acute otitis media, otitis media with effusion, hearing loss and airway obstruction. METHODS: A single-centre retrospective chart review of 61 patients (36 M/25F) with different MPS subtypes (MPS I (n = 15), MPS II (n = 10), MPS III (n = 17), MPS IV (n = 15) and MPS VI (n = 4)) was conducted. The age of ENT presentation and frequency of ENT symptoms, surgeries and their distribution among MPS subtypes was studied. The relationship between ENT presentation, first ENT surgery and the age of diagnosis was also evaluated. RESULTS: Median age at the first ENT manifestation was 2.8 years, median age at MPS diagnosis 4.1 years. The great majority of patients (90%) manifested at least one ENT diagnosis; often before the diagnosis of MPS (75%). Chronic/recurrent rhinosinusitis was the most prevalent ENT diagnosis (77%), followed by upper airway obstruction (65%) and hearing loss (53%). Chronic/recurrent rhinosinusitis was the first ENT symptom to appear (median age 2.2 years), followed by otitis media with effusion (3.7 years) and hearing loss (4.5 years). At least one ENT surgery was performed in 57% of patients; in 69% before MPS diagnosis was established. Median age of the first ENT surgery was 4.1 years. ENT symptoms and surgical procedures were earliest present in MPS II. CONCLUSIONS: Our study documents high and early occurrence of various otolaryngologic symptoms in MPS and thus highlights the role of ENT specialist in prompt diagnosis of these rare diseases and their long-term management.

Adult Morquio syndrome requiring occipito-thoracic fusion.

Morquio syndrome is a relatively rare entity that is often associated with atlantoaxial instability from early childhood due to odontoid dysplasia based on a mucopolysaccharoidal disorder. Here, we present the case of a 55-year-old male patient with Morquio syndrome who developed cervical myelopathy, which is an extremely rare condition in the older population. Myelopathy developed gradually with upper-limb paresthesia and clumsiness of both hands. The patient had a characteristic "gargoyle-like" coarse face with a trunk shortening-type short stature. Imaging of the cervical spine demonstrated several problems, including diminutive structures called platyspondyly with small pedicles and fragile bone quality, hypoplasia of the C1 posterior arch that migrated into the spinal canal, and os odontoideum with atlantoaxial instability. With intraoperative navigation guidance, posterior decompression of C1 followed by occipito-cervico-thoracic spinal fusion was successfully performed in this complicated case. Clinical and radiographic outcomes were both excellent and have been maintained for 2 years postoperatively.

Atlantoaxial instability treated with free-hand C1-C2 fusion in a child with Morquio syndrome.

Mucopolysaccharidosis type IVA, also known as Morquio syndrome, is an autosomal recessive lysosomal storage disease. Skeletal dysplasia with short stature, dysplastic-hypoplastic dens (os odontoideum), ligamentous hyperlaxity, and C1-C2 instability are characteristic features. Most patients with Morquio syndrome present with compressive myelopathy at a young age as a result of a combination of C1-C2 instability and extradural soft tissue thickening; treatment generally consists of anterior decompression with occipito-cervical fusion and external orthosis. In this report, we describe the successful treatment of a young child using posterior C1-C2 fusion alone with a free-hand technique. A 3-year-old boy presented at our hospital with a 5-month history of progressive quadriparesis. A whole-body skeletal survey showed skeletal dysplasia with hypoplasia, thoracolumbar kyphosis, and atlantoaxial subluxation. Preoperative cervical imaging showed compressive myelopathy at C1-C2 and atlantoaxial subluxation. C1-C2 fixation and decompression were performed successfully. After the operation, the patient had improved strength and was able to walk independently 8 months postoperatively. Establishment of stability via C1-C2 fusion is challenging in patients with genetic disorders characterized by skeletal dysplasia because of these young patients' small bone size and deficient bone quality. In this unique case, the treatment consisted solely of C1-C2 fusion with a free-hand technique. This case report presents a new approach in the treatment of atlantoaxial instability in Morquio syndrome.

Association of Mucopolysaccharidosis Type 4A and Bartter Syndrome.

A 6-year-old Syrian boy presented with complaints of facial dysmorphism and difficulty of walking. He had coarse face, macrocephaly, pectus carinatum, x-bain deformity, kyphosis, corneal clouding, and claw hand deformity. Galactose-6 sulphatase enzyme level was 0.1 nmol/mg.17 h (reference range, > 68 nmol/mg.17 h), compatible with Morquio syndrome. On laboratory examinations, potassium level was 2.9 mmol/L (reference range, 3.5 mmol/L to 5.1 mmol/L), sodium level was 130 mmol/L (reference range, 135 mmol/L to 148 mmol/L), and chloride level was 92 mmol/L (reference range, 101 mmol/L to 109 mmol/L). Blood pH was 7.5 and bicarbonate level was 31 mEq/L. Urine sodium and chloride levels were high. Arterial blood pressure was normal and these findings were consistent with Bartter syndrome. This is the first report of a patient with the association of Bartter syndrome and mucopolysaccharidosis type 4A, which was thought to be coincidental.

An Evidence-based Approach to the Management of Children With Morquio A Syndrome Presenting With Craniocervical Pathology.

STUDY DESIGN: Retrospective case series OBJECTIVE.: The aim of this study was to review clinical and radiological outcomes of craniovertebral surgery in children with Morquio A syndrome (Mucopolysaccharidosis type IVA) and develop an evidence-based management algorithm. SUMMARY OF BACKGROUND DATA: Myelopathy secondary to craniovertebral pathology is a common cause of neurological disability in Morquio A syndrome. Previously unresolved surgical controversies include the value of surveillance, surgical indications, and operative technique. METHODS: A retrospective case-based review of children with Morquio A syndrome and craniovertebral pathology seen in a tertiary referral pediatric center from 1992 to 2016 was performed. Patients treated nonoperatively and operatively were included. Medical records and imaging were reviewed to determine clinical and radiological findings at initial assessment, before cervical spine surgery, early postoperative period, and final follow-up. The clinical outcomes of interest were neurological status and mobility at follow-up, complications, and need for further surgery. RESULTS: Twenty-seven patients were included. Surgical indications were radiological evidence of cervicomedullary compression alone (six cases) or with clinical evidence of myelopathy (12 cases). Eighteen patients (median age 6.2 years, range 3.5-15.9 years) underwent surgery, with median follow-up of 8.5 years. Occiput to upper cervical spine fusion with C1 decompression was performed in all cases with the addition of autologous calvarial graft in young patients (12 cases) and occipital-cervical plate fixation in older children (six cases). Neurological improvement occurred in 38% of cases but by one functional level only. Six of nine conservatively treated patients remained independent walkers. CONCLUSION: Surgery for craniovertebral pathology is required in the majority of children with Morquio A syndrome. Close clinical and radiological surveillance is essential for timely intervention. Occiput to cervical fusion is safe and feasible even in young patients and improves clinical and radiological parameters. LEVEL OF EVIDENCE: 4.

Late diagnosis of mucopolysaccharidosis type IVB and successful aortic valve replacement in a 60-year-old female patient.

Mucopolysaccharidosis type IVB (MPS IVB) is a very rare lysosomal storage disorder characterized by skeletal dysplasia, hearing disorder, and cardiac valvular disease. Herein, we report an extremely rare manifestation of MPS IVB in a 60-year-old female patient who underwent a successful aortic valve replacement. The patient presented with mild coarse facial features, short stature, mild dyspnea, sternal protrusion, mild lumbar hyperlordosis, and waddling gait owing to bilateral femoral head necroses and bilateral arthrosis of the knees. The patient also suffered from dyspnea, NYHA II-III. Echocardiography revealed severe stenosis of a calcified aortic valve (AVA 0.67 cm2, AVAi 0.45 cm2/m2, PG max/mean 130/80 mmHg), left ventricular hypertrophy with predominant septal thickening (18 mm) and mild left ventricle outflow tract obstruction at rest, mild mitral valve regurgitation, and dilated ascending aorta (36 mm, 26.5 mm/m2). Dyspnea resolved after septal myectomy and replacement of the aortic valve with bioprosthesis. Excretion levels and spectrum of glycosaminoglycans (GAGs) in urine were normal in the patient. We confirmed the diagnosis of MPS IVB by identifying decreased beta-galactosidase activity in isolated leukocytes (6 nmol/h/mg; controls 95-272) and by molecular genetic analyses (c.438_440delTCT and c.817_818TG>CT mutations in the GLB1 gene). Primary lysosomal storage of glycosaminoglycans was detected in fibroblasts of the aortic valve. Additional pathologies included valvular fibrosis, calcification, neovascularization, and mild chronic inflammation. In conclusion, the diagnosis of MPS IVB should be considered in older patients with cardiac valvular disease and progressive skeletal abnormality even if urinary excretion levels of GAGs are normal.

Neurophysiology of hearing in patients with mucopolysaccharidosis type IV.

BACKGROUND: Hearing impairment is a common problem in patients with mucopolysaccharidosis IV (MPS IV) throughout their life. Many of the adult patients with MPS IV exhibit permanent or severe hearing loss. However, there has been no systematic review of detailed audiological test results in MPS IV. MATERIALS AND METHODS: Fourteen individuals with MPS IV (13 MPS IVA and 1 MPS IVB; aged between 12 and 38 years old) participated in the current study. We obtained auditory neurophysiological responses (auditory brainstem responses and otoacoustic emissions test) in addition to pure-tone audiometry and middle ear function tests (tympanometry and acoustic reflexes). RESULTS: The results indicated various levels and types of hearing loss with abnormal neurophysiological responses even in those patients with MPS IVA with normal pure tone thresholds. We also found a strong relationship between height (short stature is an indicator of skeletal severity) and hearing sensitivity as well as a strong relationship between height and outer hair cell function in the inner ear (measured by otoacoustic emissions) among MPS IVA patients. CONCLUSION: The strong correlation between reduced height and hearing loss indicates that patients with severe skeletal dysplasia may be at higher risk of developing more severe hearing loss. More importantly, the spectrum of hearing disorders indicates that MPS IV patients should have annual neurophysiological hearing tests in addition to audiometric testing from an early age regardless of their skeletal severity to more carefully monitor disease progression.

Voice alterations in patients with Morquio A syndrome.

Morquio A syndrome, or mucopolysaccharidosis (MPS IV A), is an inherited lysosomal storage disorder which belongs to the group of mucopolysaccharidoses (MPSs). It is caused by N-acetylgalactosamine-6-sulfatase (GALNS) activity deficiency, which results in impaired degradation of glycosaminoglycans (GAGs), including keratan sulfate (KS) and chondroitin-6-sulfate (CS). These compounds infiltrate and disrupt the architecture of the extracellular matrix, compromising the integrity of the connective tissue. Patients with Morquio A have also been noted for exhibiting abnormalities of the larynx and vocal tract. The aim of the study was to assess voice alterations using noninvasive acoustic and electroglottographic voice analysis. Electroglottographic signal and acoustic analyses revealed considerable changes in the voices of patients with Morquio A syndrome when compared to the voices of healthy controls. Affected patients tended toward tense voice, incomplete glottal closure, increased incidence of vocal fold nodules, dysphonia, and hoarse voice. Morquio A syndrome is characterized by connective tissue disease, which adversely affects voice quality. The use of objective voice analysis makes it possible to quantitatively monitor changes in the vocal apparatus over the course of disease progression, and also allows for assessment of the effects of the enzyme replacement therapy.