Molecular genetics and metabolism, special edition: Diagnosis, diagnosis and prognosis of Mucopolysaccharidosis IVA

Abstract

Mucopolysaccharidosis IVA (MPS IVA, Morquio A syndrome) is an autosomal recessive disorder caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to the accumulation of specific glycosaminoglycans (GAGs), chondroitin-6-sulfate (C6S) and keratan sulfate (KS), which are mainly synthesized in the cartilage. Therefore, the substrates are stored primarily in the cartilage and its extracellular matrix (ECM), leading to a direct impact on bone development and successive systemic skeletal spondylepiphyseal dysplasia. The skeletal-related symptoms for MPS IVA include short stature with short neck and trunk, odontoid hypoplasia, spinal cord compression, tracheal obstruction, obstructive airway, pectus carinatum, restrictive lung, kyphoscoliosis, platyspondyly, coxa valga, genu valgum, waddling gait, and laxity of joints. The degree of imbalance of growth in bone and other organs and tissues largely contributes to unique skeletal dysplasia and clinical severity. Diagnosis of MPS IVA needs clinical, radiographic, and laboratory testing to make a complete conclusion. To diagnose MPS IVA, total urinary GAG analysis which has been used is problematic since the values overlap with those in age-matched controls. Currently, urinary and blood KS and C6S, the enzyme activity of GALNS, and GALNS molecular analysis are used for diagnosis and prognosis of clinical phenotype in MPS IVA. MPS IVA can be diagnosed with unique characters although this disorder relates closely to other disorders in some characteristics. In this review article, we comprehensively describe clinical, radiographic, biochemical, and molecular diagnosis and clinical assessment tests for MPS IVA. We also compare MPS IVA to other closely related disorders to differentiate MPS IVA. Overall, imbalance of growth in MPS IVA patients underlies unique skeletal manifestations leading to a critical indicator for diagnosis.

Genetic testing for the diagnosis and classification of joint hypermobility: a case report of 15 patients

“…The proband 2 in our study mainly presented with dislocation of hip and contractures of shoulders and elbow joints, which can't get an accurate diagnosis according to the clinical symptoms. Proband 1, proband 3 and proband 4 were diagnosed with suspected JHS/JH-related disorders, the genetic results revelated mutations in COL11A1, NALCN and GALNS, which can lead to Stickler syndrome, CLIFAHDD syndrome, Mucopolysaccharidosis IVA, respectively [16,[23][24][25][26]. The genetic results corrected the first clinical diagnosis.…”

Modelling Morquio A syndrome: an anthropometric study of body characteristics and stature

“…Creating a universal model of the body stature of MPS IVA is a challenging task because of the wide spectrum of disease severity. There is a scarcity of literature reporting detailed anthropometric data for children with MPS diseases [5,6]. Constructing such a model requires measurement tools of maximum precision and monitoring of development parameters, specifically age ranges.…”

“…Analysis of anthropometric measurements among MPS IVA patients allowed for distinction of features which deviated from the normal population. The thoracic spine from T1 to T12, as well as the lumbar region of the spine from L1 to L5, stops growing early, causing MPS IVA patients to have a short trunk [6]. The most common deformity for MPS IVA presents in the lower extremities of the knee and ankle valgus.…”

“…The shoulders were narrow and the chest presented pectus carinatum deformities. This is a marked deformity of the anterior chest wall caused by rib overgrowth -compared to other parts of the body -which restricts the lungs [6]. Because of degenerative changing in body stature, MPS IVA may be misdiagnosed as spondyloepiphyseal dysplasia or other musculoskeletal disorders [22], however a typical characteristic for MPS IVA are hypermobile joints secondary to ligamentus laxity [23].…”

“…Patients with MPS IVA are severely affected in growth; their final adult height can be used as an indicator of disease severity. The phenotypic spectrum for MPS IVA ranges from a rapid progressive, early onset classical form -, to a slow progressive, late onset non classical form [6].…”