Hallazgos ecocardiográficos de pacientes pediátricos con mucopolisacaridosis tipo IV-A con mutación c.901G>T en el gen GALNS en un centro de salud de cuarto nivel de Colombia en el periodo de 2012-2019

La mucopolisacaridosis tipo IV-A es un trastorno de almacenamiento lisosómico poco frecuente, cuya manifestación clínica más evidente es la disostosis múltiple. Alteraciones multiorgánicas se han descrito en este tipo de pacientes, sin embargo, las manifestaciones cardiovasculares no han sido descritas con gran énfasis. Esta investigación tuvo como objetivo principal describir los hallazgos ecocardiográficos en pacientes pediátricos con mucopolisacaridosis tipo IV-A con mutación c.90iG>T en el gen GALNS. Se realizó un estudio descriptivo de serie de casos que incluyó pacientes con diagnóstico confirmado (clínico, bioquímico y molecular) de mucopolisacaridosis tipo IV-A; los pacientes asistieron a una institución hospitalaria en Pereira, Colombia, entre 2012 y 2019, donde se valoraron parámetros ecocardiográficos. Se incluyeron diez pacientes con edades comprendidas entre 3 y 18 años, media de 10. Las anomalías cardiacas identificadas fueron regurgitación mitral trivial RM en 4 de 10 pacientes, dilatación del anillo aórtico en 9 de 10, dilatación de la aorta ascendente, dilatación del arco transverso y del istmo aórtico en 1 de 10, área subaórtica levemente engrosada sin estenosis e hipertrofia ventricular izquierda concéntrica leve en 1 de 10 pacientes. La función ventricular fue normal en todos los pacientes. Los hallazgos ecocardiográficos más frecuentes fueron dilatación del anillo aórtico y regurgitación trivial de la válvula mitral, adicionalmente, pueden encontrarse válvulas mitral y aórtica engrosadas e hipertrofia ventricular izquierda, por lo que es importante una valoración periódica por cardiología pediátrica.

Mucopolysaccharidosis IV-A is a rare lysosomal storage disorder, whose most evident clinical manifestation is multiple dysostosis. Multiorgan disorders have been described in this type of patients, however, the Cardiovascular manifestations have not been described with greater emphasis. The main objective of this research was to describe the echocardiographic findings in pediatric patients with type IV-A mucopolysaccharidosis with c.901G>T mutation in the GALNS gene. A descriptive case series study was carried out, which included patients with a confirmed diagnosis (clinical, biochemical and molecular) of mucopolysaccharidosis type IV-A; the patients were attended a hospital institution in Pereira, Colombia, between 2012 and 2019, where echocardiography parameters were evaluated. Ten patients with ages ranging from 3 to 18 years, average 10, were included. The cardiac abnormalities identified were trivial mitral regurgitation in 4 of 10 patients, aortic annulus dilation in 9 of 10, dilatation of the ascending aorta, dilatation of the transverse arch and aortic isthmus in 1 of 10, slightly thickened subaortic area without stenosis and mild concentric left ventricular hypertrophy in 1 of 10 patients. Ventricular function was normal in all patients. The most frequent echocardiography findings were dilatation of the aortic annulus and trivial regurgitation of the mitral valve, additionally, thickened mitral and aortic valves and left ventricular hypertrophy may be found, so periodic evaluation by pediatric cardiology is important.

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)

Surgical strategies of atlantoaxial dislocation in mucopolysaccharidosis IVa / 中华骨科杂志

Objective:To discuss the surgical strategies of atlantoaxial dislocation in children with mucopolysaccharidosis IVA.Methods:8 cases of atlantoaxial dislocation in children with mucopolysaccharidosis IVA treated with posterior atlantoaxial reduction, decompression, bone graft and internal fixation from April, 2019 to October, 2020 were retrospectively analyzed, including 6 males and 2 females, aged 6.2±3.1 years (range, 2-10 years). All the 8 children had lower limb weakness and walking instability, and some of them could not even stand and walk, and all of them had odontoid hypoplasia, atlantoaxial dislocation and systemic skeletal dysplasia. Measures, including American Spinal injury Association (ASIA) grade, modified atlanto-dental interval (mADI) and reduction rate, screw placement type and fusion of bone graft, were recorded and analyzed.Results:The follow-up time was 17.8±7.4 months (range, 8-27 months). The total operation time was 144.0±43.1 mins (range, 90-220 min) and the blood loss during the surgery was 89.1±55.1 ml (range, 15-180 ml). The ASIA grade were 3 cases of "C" level, 4 cases of "D" level and 1 case of "E" level before the operation, and 1 case of "C" level, 1 case of "D" level and 6 cases of "E" level at the latest follow-up. The mADI reduced from 7.38±2.62 mm pre-surgery to 2.50±1.60 mm ( t=5.71, P=0.001). The reduction rate of the latest follow-up mADI was 65.0%±26.3%. 31 pedicle screws were inserted, including 26 Type I screws (83.9%), 4 Type II screws (12.9%) and 1 Type III screw (3.2%), and no injury of spinal cord or blood vessels were observed associated with the Type III screw. One unilateral axial lamina screw was used in 1 case. 5 patients showed fusion (autogenous bone) 6 months after the surgery, 2 patients got fusion (allogeneic bone) 1 year after the surgery, and other patients showed bone graft resorption (allogeneic bone) at the latest follow-up. One patient developed type II respiratory failure on the night of operation and recovered after rescue. Other patients had no complications such as vascular and nerve injury, screw loosening and so on. Conclusion:The majority of children with type IVa mucopolysaccharidosis are accompanied by absence of odontoid process. If such children are complicated with atlantoaxial dislocation and cervical spinal canal stenosis resulting in cervical spinal cord injury, timely surgical intervention should be carried out. Posterior atlantoaxial fusion is a safe and effective surgical method. As children have the characteristics of multi-system involvement, multi-disciplinary cooperation may be needed to ensure perioperative safety.

Síndrome de Morquio, una afección infrecuente / Morquio syndrome, a rare condition

Introducción: el síndrome de Morquio es una rara enfermedad hereditaria autosómica recesiva, caracterizada por la presencia de un trastorno del metabolismo de los glúcidos, generando dismi- nución de la calidad de vida. Caso clínico: recién nacido a término de 37.6 semanas con APGAR 7-9, que minutos después de nacido muestra signos de cianosis distal y bucal, acompañado de disminución en la saturación de oxígeno al 70%. Posteriormente, se identificaron características fenotípicas y manifestaciones clínicas que permitieron la sospecha diagnóstica de esta enferme- dad, lo que se corroboró mediante estudio genético. Conclusiones: El diagnóstico de síndrome de Morquio se logró establecer en los primeros momentos del nacimiento, las manifestaciones observadas en el caso que se presenta fueron las clásicas que informa la literatura médica, el estudio genético confirmó el diagnóstico.

Introduction: Morquio syndrome is a rare autosomal recessive hereditary disease, characterized by the presence of a carbohydrate metabolism disorder, generating a decrease in the quality of life. Clinical case: newborn of 37.6 weeks with APGAR 7-9, who shows signs of distal and oral cyanosis, accompanied by a decrease in oxygen saturation to 70% minutes after birth. Subse- quently, the diagnostic suspicion of this disease was identified due to the phenotypic characteris- tics and clinical manifestations, which was corroborated by genetic study. Conclusions: The diagnosis of Morquio syndrome was established in the first moments of birth, the manifestations observed in the case presented were the classic ones reported in the medical literature, the gene- tic study confirmed the diagnosis

A second reported malignancy in a patient with Morquio syndrome

Morquio syndrome is a rare lysosomal storage disease that affects multiple organ systems. However, it is rarely associated with malignancy. We present the case of a 30-year old man with Morquio syndrome associated with gastric adenocarcinoma. This case also demonstrates two other findings that have not been previously described in patients with Morquio syndrome - malrotation of brainstem and cerebellum, without clinical neurologic deficit, and persistence of fetal lobulation in the kidneys.

Results of surgical treatment in the craniocervical junction in mucopolysaccharidosis / Resultados do tratamento cirúrgico na junção craniocervical nas mucopolissacaridoses / Resultados del tratamiento quirúrgico en la unión craneocervical en las mucopolisacaridosis

ABSTRACT Objective: Evaluate the results after decompression and stabilization of craniocervical junction in patients with mucopolysaccharidosis (MPS). Method: Retrospective study of 10 patients with MPS through the analysis of medical records and additional tests. Result: All patients with mid-term and long-term follow-up achieved consolidation of the arthrodesis and 87.5% had neurological improvement of Nurick score. Conclusion: Early diagnosis and intervention in cases of stenosis and/or craniocervical instability of patients with MPS provide patients a good recovery of neurological function, despite the great technical difficulty and risk of complications.

RESUMO Objetivo: Avaliar os resultados após a descompressão e estabilização da junção craniocervical em pacientes portadores de mucopolissacaridose (MPS). Método: Estudo retrospectivo de 10 pacientes portadores de MPS, por meio da análise de prontuário e de exames complementares. Resultado: Todos os pacientes com acompanhamento a médio e longo prazo atingiram a consolidação da artrodese e 87,5% tiveram melhora neurológica no escore Nurick. Conclusão: O diagnóstico e a intervenção precoces em casos de estenose e/ou instabilidade craniocervical em pacientes com MPS proporcionam aos pacientes uma boa recuperação da função neurológica, apesar da grande dificuldade técnica e do risco de complicações.

RESUMEN Objetivo: Evaluar los resultados después de la descompresión y estabilización de la unión craneocervical en pacientes con mucopolisacaridosis (MPS). Método: Estudio retrospectivo con 10 pacientes con mucopolisacaridosis, a través del análisis de las historias clínicas y de pruebas complementarias. Resultado: Todos los pacientes con seguimiento a medio y largo plazo alcanzaron la consolidación de la artrodesis y 87,5% presentaron mejoría neurológica de la puntuación Nurick. Conclusión: El diagnóstico e intervención temprana en casos de estenosis y/o inestabilidad craneocervical en pacientes con MPS proporcionan a los pacientes una buena recuperación de la función neurológica, a pesar de la gran dificultad técnica y el riesgo de complicaciones.

Relationship Between Patient-Reported Outcomes and Clinical Outcomes in Patients With Morquio A Syndrome

Abstract This cross-sectional analysis assessed the correlation between patient-reported outcomes (PROs) and clinical outcomes in 24 German patients with Morquio A. Clinical outcomes included 6-minute walk test (6MWT), 3-minute stair climb (3MSC) test, and joint range of motion as measures for endurance/mobility, forced vital capacity (FVC) and maximum voluntary ventilation (MVV) as measures for respiratory function, and height as an important manifestation. The PROs included the EuroQoL (EQ) 5D-5L (EQ5D-5L), to measure health-related QoL (HRQoL), and patients' rating of their ability to walk, climb, or breathe. In adults, endurance and pulmonary function measures and height showed strong and statistically significant correlation with the patients' EQ5D-5L (6MWT: R = .884, 3MSC test: R = .852, FVC: R = .815, MVV: R = .825, height: R = .842). The adult patients' rating of their ability to walk and climb also correlated strongly with 6MWT (R = .839) and 3MSC test (R = .700) results. Improvements in these clinical outcomes may be robust surrogate parameters of a better EQ5D-5L/HRQoL in patients with Morquio A.

The Burden Endured by Caregivers of Patients With Morquio A Syndrome: Results From an International Patient-Reported Outcomes Survey

Abstract This international survey performed by direct personal interview or mail evaluated the global burden among primary caregivers of patients with Morquio A syndrome. Collected outcomes included self-reported time spent on caregiving, proportion of daily activities (from the Mucopolysaccharidosis Health Assessment Questionnaire) requiring caregiver assistance, and how the patient's age and wheelchair use affect these. In addition, the impact of caregiving on the caregivers' relationship with family and friends, physical and mental health, and employment status and income was evaluated. Caregiver burden increased with disease progression. Adult patients always using a wheelchair required substantially more caregiving time and complete assistance with a larger proportion of daily activities than more mobile patients. In children, this was less apparent. Caregivers suffered physically and emotionally and their family and social life and financial situation were considerably impacted. Improvements in patient mobility may substantially reduce the level of caregiver support and the burden of caregiving.

Caracterización clínica, estudios genéticos, y manejo de la Mucopolisacaridosis tipo IV A / Mucopolysaccharidosis type IV A (Morquio Syndrome type A): clinical features, genetic studies, preventive management of complications and genetic counseling

Introducción: la Mucopolisacaridosis tipo IV A (OMIM #253000), es una enfermedad autosómica recesiva que pertenece al grupo de enfermedades de depósito lisosomal, esta fue descrita inicialmente por Luis Morquio, cuya etiología es la deficiencia de la enzima N-acetil-galactosamina-6-sulfato sulfatasa, favoreciendo el depósito intracelular de queratán sulfato y condroitin-6-sulfato, llevando al espectro de manifestaciones clínicas que caracterizan este síndrome como son: baja talla, anormalidades vertebrales, opacidades corneales, inteligencia conservada, entre otras. Mediante radiografía de tórax y de extremidades inferiores se pueden observar las vértebras ovoides o en cuña y alteraciones en huesos largos, respectivamente. Objetivo: revisar sobre las generalidades de la MPS IV A, sus características clínicas, complicaciones, los estudios genéticos, la asesoría genética y su manejo preventivo. Conclusiones: las pruebas de laboratorio como el test de cloruro de cetilpiridinio o la albúmina ácida son esenciales para el diagnóstico. En cuanto al tratamiento hasta la fecha no existe una terapia de reemplazo enzimático por ello los cuidados son preventivos, y el manejo de estas personas debe ser interdisciplinario (medicina, nutrición, psicología, entre otros).

Background: mucopolysaccharidosis IV A (OMIM # 253000), belongs to the group of lysosomal storage diseases, this was first described by Luis Morquio, whose etiology is a deficiency of the enzyme N-acetylgalactosamine-6-sulfate sulfatase, favoring the deposit intracellular queratán sulfate and chondroitin-6-sulfate, leading to the spectrum of clinical manifestations that characterize this syndrome are short stature, vertebral abnormalities, corneal opacities, preserved intelligence, among others. X-ray can see the vertebrae ovoid or wedge, and alterations in long bones. Objetive: make a general overview of MPS IV A, its clinical features, complications, genetic testing, genetic counseling and preventive management. Conclusions: laboratory tests as test test cetylpyridinium chloride or acid albumin essential for diagnosis. As for treatment to date there is no enzyme replacement therapy are therefore preventive care, and management of these people should be interdisciplinary (medicine, nutrition, psychology, etc.).