Morquio-Brailsford Syndrome Research Articles

A pictorial review of the radiographic skeletal findings in Morquio syndrome (mucopolysaccharidosis type IV).

Morquio syndrome, also known as Morquio-Brailsford syndrome or mucopolysaccharidosis type IV (MPS IV), is a subgroup of mucopolysaccharidosis. It is an autosomal recessive lysosomal storage disorder. Two subtypes of Morquio syndrome have been identified. In MPS IVA, a deficiency in N-acetylgalactosamine-6-sulfate sulfatase interrupts the normal metabolic pathway of degrading glycosaminoglycans. Accumulated undigested glycosaminoglycans in the tissue and bones result in complications leading to severe skeletal deformity. In MPS IVB, a deficiency in beta-galactosidase results in a milder phenotype than in MPS IVA. Morquio syndrome presents a variety of clinical manifestations in a spectrum of mild to severe. It classically has been considered a skeletal dysplasia with significant skeletal involvement. However, the extraskeletal features can also provide valuable information to guide further work-up to assess the possibility of the disorder. Although the disease involves almost all parts of the body, it most commonly affects the axial skeleton, specifically the vertebrae. The characteristic radiologic findings in MPS IV, such as paddle-shaped ribs, odontoid hypoplasia, vertebral deformity, metaphyseal and epiphyseal bone dysplasia, and steep acetabula, are encompassed in the term "dysostosis multiplex," which is a common feature among other types of MPS and storage disorders. Myelopathy due to spinal cord compression and respiratory airway obstruction are the most critical complications related to mortality and morbidity. The variety of clinical features, as well as overlapping of radiological findings with other disorders, make diagnosis challenging, and delays in diagnosis and treatment may lead to critical complications. Timely imaging and radiologic expertise are important components for diagnosis. Gene therapies may provide robust treatment, particularly if genetic variations can be screened in utero.

Novel data on growth phenotype and causative genotypes in 29 patients with Morquio (Morquio-Brailsford) syndrome from Central-Eastern Europe

Mucopolysaccharidosis type IVA, also known as Morquio (Morquio-Brailsford) syndrome results from accumulation of keratan sulfate (KS) and chondroitin-6-sulfate (C6S), whereas the primary cause is mutations in the gene encoding galactosamine (N-acetyl)-6-sulfatase (GALNS). Phenotypically it seems to be a well-defined condition, with two main clinical forms: mild (attenuated) and severe, which are determined based on a combination of symptoms, i.e., enzymatic activity of GALNS, age of onset, and symptom severity. Nevertheless, the natural history of MPSIVA in relation to specific anthropometric parameters (growth, head circumference, body proportions, and face phenotype) is not precisely characterized. The aim of our work was to analyze the aforementioned anthropometric parameters, including correlation to molecular data (causative GALNS mutations).

Lower Extremity Deformity Management in MPS IVA, Morquio-Brailsford Syndrome: Preliminary Report of Hemiepiphysiodesis Correction of Genu Valgum.

Morquio-Brailsford syndrome or mucopolysaccharidosis type IV-A (MPS IV-A) is an inherited metabolic disease in which skeletal deformities can be extreme. An international registry has shown that 46% of patients are unable to walk 200 m and 30% use a wheelchair. Lower limb surgery is performed to restore alignment with the expectation of maintaining mobility. We are, however, not aware of reports correlating function with alignment. This study assesses the role of orthopaedic intervention with reference to anatomic and functional outcome in MPS IV-A: specifically hemiepiphysiodesis correction of genu valgum. Interrogation of the MPS patient database identified 63 patients. Patient demographic and radiographic data were collected along with information on deformity, correction, mobility, and genotype. Genu valgum was assessed by intermalleolar distance and mobility by a standardized 6-minute walk test. Sequential hip anatomy was assessed radiographically. Twenty-six surgical hemiepiphysiodesis episodes were performed on 23 patients. There were no cases of implant failure, loosening, or infection. The average intermalleolar distance reduction was 6.12 cm (paired t test, P=0.0001) (95% confidence interval, 7.6-4.7 cm) and the mean change in 6-minute walk test was +69.5 m (P=0.0339). There was no correlation between hip subluxation/dislocation and mobility (Fisher exact test, P=1.000), although hip parameters deteriorated over time. Three patients required repeat 8-plate insertion and 1 a femoral osteotomy. Eight-plate hemiepiphysiodesis correction of genu valgum in MPS IV-A is an effective treatment with low complication rates. The insult of surgery is minimal compared with that of osteotomy which can reduce mobility further. Our outcomes suggest that mobility is maintained or improved even in severe genotypes where mobility typically worsens. We have found hip pathology to be less debilitating, but further studies are needed to assess the effect of genu valgum correction upon femoral head subluxation and collapse.We suggest hemiepiphysiodesis should be considered as part of the treatment strategy for limb alignment in MPS IV-A patients, depending on remaining growth, mobility status, and genotype. Level IV-therapeutic case series.

The evolution of lower extremity deformity management in MPS IV A, Morquio-Brailsford syndrome

The evolution of lower extremity deformity management in MPS IV A, Morquio-Brailsford syndrome

Airway management in a patient with Morquio–Brailsford syndrome

Airway management in a patient with Morquio–Brailsford syndrome

Safe intubation in Morquio-Brailsford syndrome: A challenge for the anesthesiologist

Morquio-Brailsford syndrome is a type of mucopolysaccharidoses. It is a rare disease with features of short stature, atlantoaxial instability with risk of cord damage, odontoid hypoplasia, pectus carinatum, spine deformities, hepatomegaly, and restrictive lung disease. Neck movements during intubation are associated with the risk of quadriparesis due to cervical instability. This, along with the distortion of the airway anatomy due to deposition of mucopolysaccharides makes airway management arduous. We present our experience in management of difficult airway in a 3-year-old girl with Morquio-Brailsford syndrome posted for magnetic resonance imaging and computerized tomography scan of a suspected unstable cervical spine. As utmost sagacity during intubation is required, the child was intubated inside operation theatre in the presence of experienced anesthesiologists and then shifted to the peripheral location. Intubation was done with an endotracheal tube railroaded over a pediatric fibreoptic bronchoscope passed through the lumen of a classic laryngeal mask airway, keeping head in neutral position.

Roentgenographic diagnosis of mucopolysaccharidosis with particular reference to Morquio syndrome

Mucopolysaccharidosis (MPS) comprises a group of conditions associated with an abnormality in glycoprotein or mucopolysaccharides metabolism. Types of MPS identified are MPS I-H (Hurler's syndrome, gargoylism), MPS II (Hunter's syndrome), MPS III (Sanfilippo's syndrome), MPS IV (Morquio-Brailsford syndrome), MPS I-S (Scheie's syndrome) and MPS VI (Maroteaux-Lamy syndrome). The Hunter type is inherited as an X-linked recessive; the others are autosomal recessive. Patients with MPS IV can usually be clinically distinguished from patients with other forms of MPS; their intelligence is unimpaired, in contrast with other forms of MPS. Husler coined the term dysostosis multiplex to describe the skeletal findings.

Bilateral total hip arthroplasty in Morquio-Brailsford’s Syndrome: a report of two cases

We report two cases of bilateral cementless total hip arthroplasty in two young women affected by Morquio-Brailsford syndrome. Morquio-Brailsford disease belongs to the mucopolysaccharidoses; it shows growth retardation with disproportional dwarfism. Usually patients are affected by a severe joint degeneration from their 2nd or 3rd decade. Young age, severe dysplasia, and joint size are the main technical problems for a total hip replacement. Accurate radiographic and CT planning allows the use of standard prostheses instead of custom-made ones.

The Use of Computed Tomography to Assess Acetabular Morphology in Morquio-Brailsford Syndrome

Morquio-Brailsford syndrome (MS) is an autosomal recessive lysosomal storage disorder, a mucopolysaccharidosis, characterized by abnormal metabolism of glycosaminoglycans. Major treatable concerns in patients with MS involve C1 to C2 instability, genu valgum, and hip subluxation. Untreated hip subluxation has been shown to predispose to early onset of arthritis of the hip. Early appropriate pelvic osteotomies may restore (improve) load transmission and retard the onset of arthritis. Computed tomographic (CT) measurements can help determine the site and severity of acetabular deficiency, aiding in selection of the appropriate acetabular procedure. Acetabular morphology in MS has not been described in the literature. The purpose of this study was to evaluate morphology (shape) of the acetabulum in MS using two-dimensional (2-D) CT scans. To assess the acetabular roof, the acetabular index was measured on anteroposterior radiographs of the pelvis. Various CT measures were used to assess the acetabular anatomy in the axial plane. The average acetabular index on the anteroposterior radiographs of the pelvis was 33 degrees (average age-matched difference from normal, 12 degrees). Two-dimensional CT (axial cuts) showed that the average acetabular anteversion angle was close to normal, measuring 10.9 degrees. The average anterior acetabular index was 58.8 degrees (average age-matched difference from normal, 10.6 degrees), and posterior acetabular index was 53.8 degrees (average age-matched difference from normal, 3.8 degrees). Calculated axial acetabular index ranged from 90 to 133 degrees (mean, 112.6 degrees; average difference from normal, 14.5 degrees). Two-dimensional CT of the hip in patients with MS demonstrated a severe dysplasia of the anterior acetabular wall and the roof of the acetabulum, although the acetabular version was normal. Treatment of hip dysplasia in MS should focus on increasing the overall depth of the acetabulum to better contain the femoral head. Two-dimensional CT is recommended before bony acetabular procedures to assess the degree of acetabular deficiencies. Computed tomography of the acetabulum is helpful in preoperative decision making and planning before an acetabular procedure in patients with Morquio-Brailsford syndrome.

Early-onset osteoporosis with high bone turnover in children with Morquio-Brailsford syndrome

Early-onset osteoporosis with high bone turnover in children with Morquio-Brailsford syndrome

The life and work of the Birmingham radiologist Dr James Brailsford (1888-1961).

James Brailsford went from humble beginnings to become an eminent radiologist through his ability, determination and immense diligence. He made a late start in medicine but became one of the world's leading authorities on skeletal diseases; he wrote the classic textbook The Radiology of Bones and Joints and described the eponymous Morquio-Brailsford syndrome. In 1934 he was elected first President of the British Association of Radiologists, of which he was founder. This later became the Faculty of Radiologists at the Royal College of Surgeons and is now the Royal College of Radiologists.

OCCIPITO-ATLANTO-AXIAL FUSION IN MORQUIO-BRAILSFORD SYNDROME

In 17 patients (eleven males, six females) with Morquio-Brailsford syndrome (mucopolysaccharidosis IV) we have used onlay femoral and tibial autografts placed posteriorly and secured to the laminae of C1 and C2 to obtain satisfactory occipito-C1/C2 posterior fusion. They were immobilised postoperatively in a halo-plaster body jacket for four months. The age at operation varied between three and 28 years. Those with myelopathic symptoms of recent onset made some recovery, but severely myelopathic patients showed little or no recovery. We advise prophylactic occipitocervical fusion in these patients since the cartilaginous dens is not strong enough to ensure atlanto-axial mechanical stability.

Anaesthesia for Urinary Diversion with Ileal Conduit in a Patient with Morquio-Brailsford Syndrome

Anaesthesia for Urinary Diversion with Ileal Conduit in a Patient with Morquio-Brailsford Syndrome

The Schwartz-Jampel syndrome: Its clinical, physiological and histological expressions

Patients with the Schwartz-Jampel syndrome represent an example of continuous muscle fiber activity at rest. Abolition of the continuous repetitive discharges with curare showed that this was not myotonia as previously reported. The likelihood that the abnormal discharges originated from the muscle component of the neuromuscular junction rather than the nerve was suggested by the observation that spontaneous electrical activity persisted long after peripheral nerve injury in 1 of the cases. Electron-microscopic examination of biopsy specimens showed marked dilatation of the endoplasmic reticulum of skin fibroblasts and moderate dilatation of the sarcoplasmic reticulum of muscle fibres. Tissue culture studies of the fibroblasts revealed a low level of lipid label incorporation representing a non-specific depression of the synthetic machinery of these cells. These studies failed to demonstrate any mucopolysaccharide abnormality, even though the radiologic findings in 1 of the cases were consistent with those found in the Morquio-Brailsford syndrome. Histochemical evaluation showed hypertrophy of both Type I and II fibers with SDH activity uniformly high in both fiber types. AChE staining revealed marked diffuse activity throughout the sarcoplasm of the muscle similar to that reported in embryonic muscle. These findings suggest the possibility that the abnormality in this syndrome occurs during fetal development.

LATIN AMERICAN PEDIATRIC LITERATURE IN ENGLISH ABSTRACTS

Eduardo Marcondes and Ondina Botelho DoNascimento Fo.: Mucopolysccharidoses. Pediatría Pratica (São Paulo) 40:245 (July) 1969. This paper presents a review of the mucopolysaccharidoses (MPS) and contributes five additional patients studied by the authors. Classification of the MPS is divided into six groups: Group 1 is the typical form, the type example being Hurler's Syndrome, of which there have been more than 250 cases reported in the literature. The clinical features are classical and this form of the disease is characterized by progressive mental deficiency as well as typical facial, skin, and bone changes. Urine contains large quantities of mucopolysaccharides, especially chondroitin sulfate—type B, and heparin sulfate, and there are metachromatic changes in leukocytes and in the bone marrow. Group 2 is a unique entity and genetically determined. Clinical features are similar to Group 1, although the mental deterioration is slower. It is thought that there may be a somewhat lesser excretion of chondroitin B in the urine in Group 2. Group 3 is characterized by marked mental retardation with minimal radiological changes. Opacification of the cornea does not occur and usually there are no cardiovascular alterations. Heparin sulfate is the principal mucopolysaccharide excreted in the urine. Group 4, usually known as the Morquio-Brailsford or Ullrich syndrome, is another typical form characterized principally by alterations in the spinal column and truncal bone structure, but without significant mental deterioration. In the Ullrich form, opacities of the cornea are present; hepatosplenomegaly is not characteristic; a keratosulfaturia is present. In Group 5, originally described as a variant of Group 2, there is urinary excretion of both the mucopolysaccharides chondroitin and heparin sulfate.

Spinal deformities with paraplegia in two sisters with Morquio-Brailsford syndrome

1. Two sisters with spinal deformities and paraplegia are described.2. Apart from the original symptoms of Morquio-Brailsford syndrome the patients had the following signs:(a) Heart changes;(b) Positive test revealing presence of excessive amounts of mucopoly-saccharides in the urine, and the following signs of ‘storage syndrome’;(c) Presence of metachromatic granules in the leukocytes;(d) Corneal clouding visible with naked eye in one case (A.V.) and with the aid of slit-lamp in the other case (F.V.);(e) Retarded intellect.3. The Morquio-Brailsford syndrome belongs to constitutional disorders of connective tissue when excessive amounts of mucopolysaccharides can be revealed in the urine.See also: Discussion.