Musculoskeletal anomalies in children with Mucopolysaccaridoses

Introduction The accumulation of glycosaminoglycan (GAGs) in the tissues in Mucopolysaccharidoses (MPS) can lead to skeletal anomalies (DYSOSTOSIS MULTIPLEX) and to soft tissue impairments (neural or medullar compression, joint stiffness, tenosynovitis). Here is a review of orthopedic issues frequently encountered in patients with MPS. Material and methods Surgery may be justified at different age and according to the type of MPS. Different surgical approaches and their indications are exposed in the article. Results The article exposes indications and techniques for orthopedic issues in MPS children: cervical stenosis, cervical instability, kyphosis, hip dysplasia and hip dislocation, genu valgum. Conclusion Various musculoskeletal anomalies can be found in patients with mucopolysaccharidoses. Neurological impairments are frequently seen due to cervical stenosis or instability and should be early detected with regular MRI of the cervical spine. Well-codified management should lead to favorable functional results and maintain functional and walking abilities.

Total Hip Arthroplasty in a Patient with Mucopolysaccharidosis Type IVB

Introduction. Morquio syndrome or mucopolysaccharidosis (MPS) type IV is a rare autosomal recessive lysosomal storage disease, characterized by abnormal metabolism of glycosaminoglycans associated with specific skeletal deformities, also known as dysostosis multiplex. Case Presentation. We present the case of a 23-year-old patient with advanced osteonecrosis of the femoral head (ONFH) on both sides due to Morquio syndrome. A diagnosis of mucopolysaccharidosis type IVB was made after extensive genetic profiling. The patient had the condition for a long time. At 7 years old, the patient was treated with bilateral pelvic Salter’s osteotomy. Afterward, the patient was able to walk freely but could never take part in sports. At 22 years old, pain in the hip increased, and magnetic resonance imaging showed a bilateral femur head necrosis. Hence, the patient underwent cementless total hip arthroplasty (THA). Intraoperatively, a periprosthetic fracture occurred. Therefore, revision surgery with internal fixation was performed on the next day. Postoperatively, a weight-bearing restriction of 20 kg on the left leg was imposed for 6 weeks. The patient made a full recovery and was able to move without residual complaints. Annual orthopedic evaluation in patients treated with surgical intervention is recommended. Discussion. Orthopedic challenges for mucopolysaccharidoses and corresponding bone alterations, known as dysostosis multiplex, involving trunk and limbs with typical radiological findings have been well described. The hip is invariably involved, with dysplasia affecting the femoral neck (coxa valga), femoral epiphysis (loss of sphericity, osteonecrosis), and a flared hypoplastic iliac wing. Symptomatic therapy consists, on the one hand, of a surgical procedure and, on the other hand, a variety of supportive measures. However, the management of joint replacement in lysosomal storage diseases has not been well reported. All patients with MPS should be considered at high risk for surgical intervention requiring anesthesia because of airway and cardiac disease manifestations. In the case of a need for THA, we recommend cemented stem fixation because of the overall poor bone quality in patients with Morquio syndrome.

Hurler’s disease presenting with quadriparesis and short stature

Mucopolysachharidosis are a broad spectrum of rare lysosomal storage disorder caused by deficiency of enzymes responsible for degradation of glycosaminoglycans (GAG), thus leading to accumulation of GAG in various body tissues leading to somatic and neurological manifestations. General phenotype includes coarse facies, corneal clouding, hepatosplenomegaly, dysostosis multiplex etc. Detailed clinical and radiological evaluation and identification of type of GAG excreted in urine narrows the diagnostic possibilities. Definitive diagnosis requires assay of specific enzymes in various tissues. Till date 14 different types of MPS including subtypes are identified. We report a case of 4 years old male child presented with short stature, spastic quadriparesis, bony abnormalities and hepatosplenomegaly without intellectual impairment.

Morquio B Disease. Disease Characteristics and Treatment Options of a Distinct GLB1-Related Dysostosis Multiplex

Morquio B disease (MBD) is an autosomal recessive GLB1-gene-related lysosomal storage disease, presenting with a peculiar type of dysostosis multiplex which is also observed in GALNS-related Morquio A disease. MBD may present as pure skeletal phenotype (pure MBD) or in combination with the neuronopathic manifestations seen in type 2 (juvenile) or type 3 (late onset) GM1 gangliosidosis (MBD plus). The main skeletal features are progressive growth impairment, kyphoscoliosis, coxa/genua valga, joint laxity, platyspondyly and odontoid hypoplasia. The main neuronopathic features are dystonia, ataxia, and intellectual/developmental/speech delay. Spinal cord compression occurs as a complication of spinal dysostosis. Chronic pain is reported, along with mobility issues and challenges with daily living and self-care activities, as the most common health concern. The most commonly reported orthopedic surgeries are hip and knee replacements. Keratan sulphate-derived oligosaccharides are characteristic biomarkers. Residual β-galactosidase activities measured against synthetic substrates do not correlate with the phenotype. W273 L and T500A are the most frequently observed GLB1 variants in MBD, W273L being invariably associated with pure MBD. Cytokines play a role in joint destruction and pain, providing a promising treatment target. In the future, patients may benefit from small molecule therapies, and gene and enzyme replacement therapies, which are currently being developed for GM1 gangliosidosis.

Mucolipidoses Overview: Past, Present, and Future

Mucolipidosis II and III (ML II/III) are caused by a deficiency of uridine-diphosphate N-acetylglucosamine: lysosomal-enzyme-N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase, EC2.7.8.17), which tags lysosomal enzymes with a mannose 6-phosphate (M6P) marker for transport to the lysosome. The process is performed by a sequential two-step process: first, GlcNAc-1-phosphotransferase catalyzes the transfer of GlcNAc-1-phosphate to the selected mannose residues on lysosomal enzymes in the cis-Golgi network. The second step removes GlcNAc from lysosomal enzymes by N-acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase (uncovering enzyme) and exposes the mannose 6-phosphate (M6P) residues in the trans-Golgi network, in which the enzymes are targeted to the lysosomes by M6Preceptors. A deficiency of GlcNAc-1-phosphotransferase causes the hypersecretion of lysosomal enzymes out of cells, resulting in a shortage of multiple lysosomal enzymes within lysosomes. Due to a lack of GlcNAc-1-phosphotransferase, the accumulation of cholesterol, phospholipids, glycosaminoglycans (GAGs), and other undegraded substrates occurs in the lysosomes. Clinically, ML II and ML III exhibit quite similar manifestations to mucopolysaccharidoses (MPSs), including specific skeletal deformities known as dysostosis multiplex and gingival hyperplasia. The life expectancy is less than 10 years in the severe type, and there is no definitive treatment for this disease. In this review, we have described the updated diagnosis and therapy on ML II/III.

Hurler’s Syndrome - A Case Report (Mucopolysaccharidosis Type-1H)

A girl named Tania, aged 5yrs was brought to Shaheed Ziaur Rahman Medical College Hospital, Bogra with the complains of swelling of both legs for 5days & low grade intermittent fever for 1month & she also had severe mental retardation, facial dysmorphism, hepatosplenomegaly, umbilical hernia, corneal clouding, large calvaria & features of dysostosis multiplex. Her clinical as well as radiological features arouse strong suspicion suffering from a rare genetic disease (autosomal recessive) hurler’s syndrome though it wasn’t confirmed by deficiency of specific enzyme or urinary excretion of GAG (glycosaminoglycan).TAJ 2011; 24(2): 148-151