Mucopolysaccharidosis VI and effects on growth of the apical bases: a case report.

OBJECTIVE: Mucopolysaccharidosis (MPS) VI is a rare disorder caused by an autosomal recessive mutation in the short arm of chromosome 5 (5q12-13) leading to an N-acetylgalactosamine-sulfatase lysosomal enzyme deficiency and numerous systemic clinical changes. The oral and maxillofacial complex may exhibit tooth eruption anomalies, macroglossia, gingival hypertrophy, mouth breathing, increased lower facial height, open bite, retrognathia, and progressive TMJ arthrosis. This report describes craniofacial growth changes in two MPS VI patients, sisters and daughters of outbred parents, who were longitudinally monitored from 11 to 15 years of age. STUDY DESIGN: Skull lateral teleradiography and cephalometric tracings were performed. The measurements were assessed in the anteroposterior and vertical directions based on protocols by McNamara and Usp/Unicamp and compared to the normal reported ranges. RESULTS: A similar skeletal class III malocclusion was observed in both patients. The jaw was retruded, the anterior skull base decreased, and the mandibular body was normal or larger than normal. The vertical growth direction differed between the patients; one was hyperdivergent, while the other was hypodivergent. CONCLUSIONS: By understanding the craniofacial growth changes in MPS VI patients, new treatment options may be developed for affected patients.

Evaluation of oral manifestations of patients with mucopolysaccharidosis IV and VI: clinical and imaging study.

OBJECTIVE: The aim of this study is to assess oral manifestations in patients with mucopolysaccharidosis IV (MPS IVA) and mucopolysaccharidosis VI (MPS VI). MATERIALS AND METHODS: Seventeen patients were assessed, nine with MPS IVA and eight with MPS VI, treated at the Medical Genetics Outpatient Clinic of Hospital Universitário Alcides Carneiro (HUAC) in Campina Grande, Paraíba State, Brazil. Assessments included clinical and intraoral examinations, analysis of occlusal function, and panoramic X-rays. RESULTS: Among all, 64.7% of the patients had unerupted teeth and 52.9% of them had enamel hypoplasia. Regarding the temporomandibular joint, 88.2% of the patients showed flattening of the mandibular condyle, 52.9% showed condylar hypoplasia, and all of them showed decreased mobility. Enamel hypoplasia was observed only in patients with MPS IVA (p < 0.05). On the other hand, only MPS VI patients presented with anterior open bite, restricted mouth opening (p < 0.05), and a higher rate of unerupted teeth, hyperplastic tooth follicle, and condylar defects (p < 0.05). CONCLUSIONS: Enamel hypoplasia was observed only in patients with MPS IVA, whereas anterior open bite was observed only in patients with MPS VI. Abnormal findings in the maxillomandibular complex were more frequent in patients with MPS VI. CLINICAL RELEVANCE: The relevant frequency of MPS VI and IVA in the sample allows us to compare the changes occurring in both groups of patients, therefore enabling us to further comprehend the oral manifestations in specific types of MPS.

Advantages of early replacement therapy for mucopolysaccharidosis type VI: echocardiographic follow-up of siblings.

Mucopolysaccharidosis type VI (Marateaux-Lamy syndrome) is an autosomal recessive disorder caused by deficient activity of the enzyme N-acetylgalactosamine-4-sulphatase (arylsulphatase B). Cytoplasmic vacuoles full of dermatan sulphate are observed in endothelial cells, myocyte, and fibroblasts, compromising the function of cardiovascular structures and contributing significantly towards morbidity and mortality. The primary objective of this study was to assess the advantages of early replacement therapy with recombinant human arylsulphatase B through the echocardiographic follow-up of sisters who started treatment at quite different ages: one at 9 years and the other at 1 year and 7 months. The older sibling showed striking mitral and aortic valve compromise when she was only 2 years old and finally needed cardiac surgery at the age of 8, even before starting enzyme replacement. Differently, the younger one has developed only mild mitral and aortic lesions throughout the follow-up period of 3 years. The two siblings had left ventricle cardiomyopathy, but partial reverse remodelling was induced by enzyme replacement therapy in both cases. The younger sibling has never received any cardiovascular drugs, whereas the older one has been using ß-blockers and diuretics in addition to enzyme therapy to cope with heart failure. Comparing the outcomes of these two sisters with a very aggressive phenotype of mucopolysaccharidosis type VI, the conclusion was that early onset of therapy may slow down the disease progression and prevent severe cardiac lesions to be established. Moreover, patients' compliance is essential for the success of treatment, as sequential echocardiographic evaluation demonstrated worsening of some cardiac lesions whenever infusions were missed.

Hydrocephalus in mucopolysaccharidosis type VI successfully treated with endoscopic third ventriculostomy.

Mucopolysaccharidosis (MPS) Type VI, or Maroteaux-Lamy syndrome, is characterized by a deficiency of the enzyme arylsulfatase B (ASB). In patients with this disorder, craniocervical compression, carpal tunnel syndrome, and communicating hydrocephalus are common. Traditionally, hydrocephalus occurring in patients with MPS VI has been treated with shunt placements. Considering obstruction of the outlets from the fourth ventricle at the craniocervical transition, the authors decided to treat a female patient with MPS VI via endoscopic third ventriculostomy. She was 12 years old and had refractory headaches. This seems to be the first reported instance of the neuroendoscopic treatment of hydrocephalus in a patient with MPS VI. The pathophysiology is briefly discussed.

Oral and systemic manifestations of mucopolysaccharidosis type VI: a report of seven cases.

Mucopolysaccharidosis (MPS) is a group of rare metabolic diseases characterized by intralysosomal accumulation of glycosaminoglycans. MPS type VI or Maroteaux-Lamy syndrome is an autosomal-recessive syndrome caused by mutations in the lysosomal enzyme arylsulfatase B. A defect in the gene leads to accumulation of nondegraded mucopolysaccharides, resulting in severe cellular dysfunction with multisystem expression. The oral manifestations of MPS VI are not well described in the literature. This paper presents a series of seven patients with MPS VI, with the description of the general clinical manifestations and focus on the still rarely studied oral manifestations of the syndrome. Among them were high palate, open bite, impacted and/or included teeth, thickening of the pericoronal follicle, and changes in the temporomandibular joint.

Spinal cord compression in young children with type VI mucopolysaccharidosis.

Spinal cord compression (SCC) is a known complication of mucopolysaccharidosis type VI (MPS VI) secondary to atlantoaxial subluxation, craniovertebral stenosis, posterior longitudinal ligament hypertrophy, or dural thickening. SCC is expected to occur in the natural history of the disease, regardless of enzyme replacement therapy (ERT), as intravenous enzyme does not cross the blood-brain barrier. We describe six MPS VI children with SCC, all diagnosed before 7years of age. Within this group, four of the children were diagnosed with SCC after the introduction of ERT. We hypothesize that these patients may illustrate the previously undetected risk of increased joint mobility caused by ERT which may have contributed to increased cervical instability by loosening the neck joint, thus leading to or unmasking SCC. We reinforce the need for close follow-up of SCC, periodic neurological assessment, spine imaging, and neurophysiology in all MPS VI patients before and during ERT. Neurophysiological abnormalities may precede changes in MRI images (as shown in patients 4 and 5 from this sample) and should, therefore, be accessed in MPS VI patient evaluations, allowing for timely intervention and better prognosis. We recognize the limitations of these data due to the small sample size and recommend further investigation into this patient population.

Sleep abnormalities in untreated patients with mucopolysaccharidosis type VI.

Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disease that affects an enzyme responsible for the degradation of glycosaminoglycans (GAGs). Partially degraded GAGs accumulate in several tissues, such as the upper airways (UA), which leads to the development of obstructive sleep apnea (OSA). Our objective was to determine the prevalence of OSA in a group of untreated patients with MPS VI and the association of OSA with clinical and echocardiographic findings. Patients aged 4 years or older with a biochemical diagnosis of MPS VI were included. Data about clinical history, physical examination, Doppler echocardiogram, and overnight polysomnography (PSG) were collected. Our results showed that of the 28 participants, 14 were boys; mean age was 98.5 months, and mean age at MPS VI diagnosis was 48.4 months. Snoring, witnessed apnea, pectus carinatum, and macroglossia were the main clinical findings. PSG results showed that 23:27 patients (85.1%) had OSA which was mild in 4, moderate in 5, and severe in 14 patients. Echocardiograms showed evidence of pulmonary hypertension (PH) in 14 patients. Lower (P = 0.037) and nadir SpO(2) (P = 0.007) were positively associated with PH. Clinical signs suggestive of respiratory abnormalities during sleep were not significantly correlated with the results of PSG. We conclude that the prevalence of OSA in patients with MPS VI was high, and the level of desaturation was positively correlated with PH. Symptoms during sleep were not associated with PSG findings, which suggests that this population should undergo routine PSG as earlier as possible. This study provides baseline data to estimate the potential impact of specific treatments in the sleep abnormalities presented by patients with MPS VI.

Manifestações cardíacas em pacientes com mucopolissacaridose VI / Cardiac manifestations in patients with mucopolysaccharidosis VI

A mucopolissacaridose tipo VI (MPS VI) é uma doença rara causada pela deficiência da enzima lisossômica arilsulfatase B, com consequente acúmulo de glicosaminoglicanos (GAGs) em vários tecidos, incluindo o cardiovascular. Com o objetivo de descrever as manifestações cardiovasculares na MPS VI, uma das principais causas de óbito, seis pacientes (4 a 13 anos) foram avaliados por exame físico, eletrocardiograma e ecocardiograma. Todos os pacientes, exceto a paciente com a menor idade, apresentaram sopro cardíaco e alterações ecocardiográficas. Os 6/6 pacientes apresentaram, no eletrocardiograma, desvio do eixo cardíaco para a direita, associado à sobrecarga atrial esquerda (1/6) ou distúrbio de condução (1/6).

Maroteaux-Lamy syndrome: orofacial features after treatment by bone marrow transplant.

PURPOSE: The objective of the present study was to emphasise the oral and dental findings of a male patient with the Maroteaux-Lamy syndrome who successfully underwent bone marrow transplantation (BMT) at the age of 22 months. CASE REPORT: A 15-year-old boy was referred to the Dentistry Division of the Catholic University of Brasília, Brazil, for dental diagnosis. General characteristics of the Maroteaux-Lamy syndrome, such as a large head, a short neck, corneal opacity, an open mouth with macroglossia, enlargement of the skull and a long anteroposterior dimension, were observed. The patient had received the benefit of a BMT at an early stage. Therefore, characteristics were presented in a moderate form, except for the skeletal symptoms. DISCUSSION: Maroteaux-Lamy syndrome, also known as mucopolysaccharidosis type VI, is a lysosomal storage disorder that is caused by a deficiency of arylsulphatase B, which leads to an accumulation of dermatan sulphate in tissues and its increased excretion in urine. The deposition of mucopolysaccharides leads to a progressive disorder involving multiple organs. It is a rare condition that is inherited as an autosomal recessive trait. The characteristic features of this disease include retardation in growth, a large head, a short neck, corneal opacity, typical facies and spinal abnormalities. The main dental findings of this syndrome include gingival hyperplasia, hypertrophy of the maxillary alveolar ridge, macroglossia, unerupted dentition, malocclusions and dentigerous cyst-like follicles. BMT is a therapeutic treatment that is given to permanently replace any disorder caused due to the deficiency of enzymes in patients with storage diseases.

Mucopolissacaridose tipo VI (síndrome de Maroteaux-Lamy): avaliação da mobilidade articular e das forças de garra e de pinça / Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome): assessment of joint mobility and grip and pinch strength

OBJETIVO: Descrever o perfil de mobilidade articular e das forças de garra e de pinça de indivíduos com MPS VI, além de sua correlação com a excreção urinária de glicosaminoglicanos, atividade da ARSB e distância percorrida no teste de caminhada de 6 minutos. MÉTODOS: Estudo observacional de 28 pacientes com MPS VI, não submetidos a tratamento específico. Todos os pacientes foram avaliados em relação à amplitude da mobilidade articular, forças de garra e de pinça, excreção urinária de glicosaminoglicanos, atividade da ARSB e teste de caminhada de 6 minutos. RESULTADOS: Demonstrou-se maior comprometimento de flexão de ombro, sem correlação com a idade, e da extensão de joelho e flexão de cotovelo, estas últimas correlacionadas negativamente com a idade. A força de garra mostrou-se comprometida em todos os pacientes, e a força de pinça apresentou correlação positiva com idade. CONCLUSÕES: A restrição da flexão de ombro, sem correlação com a idade, sugere que este achado esteja presente precocemente na MPS VI e se constitua em sinal clínico importante para suspeita diagnóstica desta doença. A amplitude da extensão de joelho e da flexão de cotovelo, por sua vez, por apresentarem correlação negativa com a idade, são possíveis marcadores da evolução da doença. Estudos adicionais são necessários para confirmação dessas hipóteses.

OBJECTIVE: To describe the profile of joint mobility and grip and pinch strength of MPS VI patients and to correlate this with urinary excretion of glycosaminoglycans (GAGs), ARSB activity, and the distance covered in a 6-minute walking test (6MWT). METHODS: This was an observational study of 28 patients with MPS VI, who had not undergone specific treatment. All patients were assessed for amplitude of joint mobility (shoulder, elbow, and knee), grip and pinch strength and urinary GAG excretion and also performed the 6MWT. RESULTS: Shoulder flexion exhibited the greatest limitation, with no correlation with age, followed by knee extension and elbow flexion, both of which were correlated inversely with age. Hand grip strength was compromised in all patients, and pinch strength exhibited a positive correlation with age. CONCLUSIONS: The fact that restricted shoulder flexion was not correlated with age suggests that this finding is present early on in MPS VI and that it constitutes an important clinical sign that should arouse diagnostic suspicion of this disease. The amplitude of knee extension and elbow flexion, in turn, are possible markers of disease progression since they have a negative correlation with age. Further studies are needed to confirm these hypotheses.

Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome): assessment of joint mobility and grip and pinch strength.

OBJECTIVE: To describe the profile of joint mobility and grip and pinch strength of MPS VI patients and to correlate this with urinary excretion of glycosaminoglycans (GAGs), ARSB activity, and the distance covered in a 6-minute walking test (6MWT). METHODS: This was an observational study of 28 patients with MPS VI, who had not undergone specific treatment. All patients were assessed for amplitude of joint mobility (shoulder, elbow, and knee), grip and pinch strength and urinary GAG excretion and also performed the 6MWT. RESULTS: Shoulder flexion exhibited the greatest limitation, with no correlation with age, followed by knee extension and elbow flexion, both of which were correlated inversely with age. Hand grip strength was compromised in all patients, and pinch strength exhibited a positive correlation with age. CONCLUSIONS: The fact that restricted shoulder flexion was not correlated with age suggests that this finding is present early on in MPS VI and that it constitutes an important clinical sign that should arouse diagnostic suspicion of this disease. The amplitude of knee extension and elbow flexion, in turn, are possible markers of disease progression since they have a negative correlation with age. Further studies are needed to confirm these hypotheses.

[Pseudo-glaucoma in type VI mucopolysaccharidosis: case report]. / Pseudoglaucoma em mucopolissacaridose tipo VI: relato de caso.

The authors report a case of a 19-year-old patient presenting with type VI mucopolysaccharidosis, diagnosed by genetic-clinical examination, demonstrating several systemic manifestations, including ocular disorders such as: corneal opacity, elevated intra-ocular pressure and increase of corneal thickness. The authors discuss the characteristic syndromic findings and the influence of corneal thickness associated with an increase in intraocular pressure leading to unnecessary antiglaucomatous treatment.

Acute infantile cardiomyopathy as a presenting feature of mucopolysaccharidosis VI.

An infant with a diagnosis of acute infantile cardiomyopathy was subsequently shown to have mucopolysaccharidosis VI. The mucopolysaccharidoses should be included in the differential diagnosis of infantile cardiomyopathy.

Comprometimento auditivo na síndrome de Maroteaux-Lamy: apresentaçäo de um caso / Hearing loss in Maroteaux-Lamy Syndrome

A síndrome de Maroteaux-Lamy é caracterizada pelo fenótipo da s. de Hurler moderadamente grave com inteligência normal e excreçäo elevada de dermatansulfato. A deficiência de uma enzima (Aril-sulfatase B) impede a degradaçäo normal dos mucoplissacarides implicando um depósito intracelular dos complexos näo degradados. O caso em estudo apresentava o quadro clínico e laboratorial característico. Associado a disacusia condutiva bilateral causada pelo acúmulo de muco com dermatansulfato no interior da orelha média. Após a timpanostomia a audiometria continuou mostrando pequena disacusia condutiva, sugerindo que o problema também poderia estar relacionado com alteraçöes de morbilidade da cadeia ossicular

[Maroteaux-Lamy's pycnodysostosis associated to external genital malformations]. / Picnodisostose de Maroteaux-Lamy associada a malformações genitais externas

The case of a seven-years-old girl with features of Maroteaux-Lamy's pycnodysostosis associated with external genital envolvement is reported. Considering the apparent and gradual increase of the clinical traits in this condition, this case may represent some contribution to its nosography. Additionally dermatoglyps technique and analysis were done which peculiar results are discussed.