A 14-year-old girl presented with a waddling gait, genu valga and mild scoliosis since the age of 5 years. Intelligence was normal. At the age of 12, growth delay was noticed. Plain films of the spine, pelvis and full-leg radiograph as well as MRI of the hip joint were performed.
Plain radiographs showed diffuse changes throughout the whole skeleton. The most remarkable findings were hypoplasia of the odontoid process, scoliosis, and flattened, wedge-shaped vertebral bodies of the entire spine (Fig. 1, 2). Full leg radiograph revealed genu valga (Fig. 3). Radiographs of the hands showed „squaring” of the metacarpal heads, delayed ossification of the carpals (particularly of the scaphoid bone) and hypoplasia of the distal radial and ulnar epiphyses (Fig. 4). Pelvic abnormalities consisted of marked hip dysplasia with flattening of the femoral heads and shallow acetabuli (Fig. 5). MRI of the hip joints showed severe collapse of the femoral heads, bilateral subluxation and joint effusion (Fig. 6). Biochemical testing suggested the diagnosis of Morquio syndrome type B, which has been confirmed by the result of genetic tests (p.Trp273Leu mutation).
Morquio syndrome or mucopolysaccharidosis (MPS) type IV is a rare genetic disorder characterised by defective degradation of keratan sulphate due to an enzymatic deficiency [1]. Two non-allelic variants, A and B, exist. Out of these two, type B is less severe and much less common [2]. It was first described by O’Brien et al. [3] in 1976. In contrast to patients with Morquio type A, in type B central nervous system is spared [4]. Skeletal manifestations, due to keratan sulphate deposition in bone and cartilage, are similar in both types and resemble those of other MPS (“dysostosis multiplex congenita”).
Clinical findings include short stature, corneal clouding and chest deformity. In contrast to other MPS, intelligence is normal.
Physical examination of the musculoskeletal system in Morquio B patients reveals ligamentous laxity of the distal joints and stiffness of the proximal ones, resulting in a waddling gait [5]. Typical radiographic features include odontoid hypoplasia, platyspondyly, tongue-like appearance of the vertebra (with “central beaking”), underdevelopment of epiphyses, hip dysplasia, shallow acetabuli, overconstricted iliac wings, coxa and genu valga. Destructive hip disease is usually more severe than in other MPS. Hand radiographs may reveal hypoplasia of the distal radius and ulna, squaring of the metacarpal heads and small or absent carpals.
MRI may be used to evaluate the degree of hip destruction. It may show steeply oblique acetabular roof with, flattening of the femoral heads and premature degenerative changes [6].
Urine test may not be sufficient for confirmation of MPS IVB and enzymatic analysis is mandatory to assess the β-galactosidase deficiency. Although the diagnosis of Morquio is based on the combination of clinical examination, biochemical and genetic testing, medical imaging may add valuable information on disease progression disease and monitoring of complications. Most importantly it allows detection of dens hypoplasia, which can lead to atlanto-axial subluxation and eventually death [7].
Although new therapeutic options are emerging, nowadays management of patients suffering from Morquio syndrome is still mainly symptomatic and limited to ensuring control of acute and chronic pain symptoms. Rehabilitation and correction of genu valga deformity are crucial to preserve functionality. Enzyme replacement therapy (ERT) and haematopoietic stem cell transplantation (HSCT) are currently under investigation for MPS IV patients. Both ERT and HSCT, although not cures, may be able to alter the natural history of the disease [8]. Other promising therapeutic approaches, such as gene therapy or small molecule therapy, are currently being scrutinised.
Mucopolysaccharidosis type IVB (Morquio syndrome type B)
1. On the lateral cervical spine radiograph, dysplasia of the odontoid process (dens) can be observed, and the vertebral bodies appear flattened (platyspondyly). Some vertebral bodies show “tongue-shaped protrusions” or a “central wedge shape,” suggesting abnormal enchondral development.
2. Full-spine imaging indicates mild scoliosis, with flattening of the vertebral bodies and relatively widened intervertebral spaces.
3. Pelvic and hip joint radiographs reveal dysplasia of the iliac wings, shallow acetabula, and irregular femoral heads, suggesting acetabular dysplasia and early degeneration of the femoral heads.
4. Full-length radiographs of both lower limbs demonstrate a significant knee varus/valgus deformity. In this particular case, there is a valgus deformity (genu valgum).
5. Hand X-rays show that the metacarpal heads appear square-like, with dysplasia of portions of the distal radius and ulna, and either smaller or absent carpal bones. These findings suggest “dysostosis multiplex” changes similar to those seen in other mucopolysaccharidoses.
1. Morquio Syndrome (MPS IV): The patient exhibits a waddling gait, short stature, hip dysplasia, ligamentous laxity, and other skeletal abnormalities, while maintaining normal intelligence. These findings align with the clinical features and imaging characteristics of the MPS IVB subtype.
2. Other Mucopolysaccharidoses (MPS series): Certain types (e.g., MPS I, II, VI) can present with multiple skeletal abnormalities. However, given the normal intelligence and specific clinical symptoms, MPS IV is more likely.
3. Other Congenital Skeletal Dysplasias (e.g., achondroplasia): These can present with limb deformities and short stature, but often have distinct cranial or vertebral findings that differ from the characteristic changes seen in mucopolysaccharidoses.
Based on the long-standing gait abnormality (“waddling gait”), genu valgum, mild scoliosis, as well as radiographic and MRI findings indicating odontoid dysplasia, hip joint destruction, and skeletal anomalies—combined with normal intellectual function—the presentation is most consistent with Morquio Syndrome (MPS IV) Type B. A definitive diagnosis usually requires enzymatic assay (β-galactosidase activity test) or genetic testing. If uncertainty remains, further enzyme activity assessment and genetic analysis are recommended to confirm the diagnosis.
1. Treatment Strategy:
- Symptomatic and Supportive Management: Currently, the focus is on symptomatic relief, including physical therapy, pain management, and orthotic support to reduce joint stress and slow progression of deformities.
- Surgical Treatment: In cases of severe hip or knee deformities or significant spinal instability, procedures such as osteotomy, joint replacement, or spinal stabilization can be considered to correct deformities, stabilize joints, and reduce pain.
- Enzyme Replacement Therapy (ERT) & Hematopoietic Stem Cell Transplantation (HSCT): Although not curative, these approaches may modify the natural course of the disease to some extent. They remain under research or partial clinical use.
- Emerging Therapies: Gene therapy and small-molecule treatments are being investigated. Ongoing clinical trials should be monitored for future possibilities.
2. Rehabilitation and Exercise Prescription (based on the FITT-VP principle):
- Frequency: Moderate exercise 3-5 times per week.
- Intensity: Light to moderate intensity is recommended, especially since high-impact activities (e.g., running, jumping) can aggravate hip and knee damage.
- Time: Begin with 15-20 minutes per session, gradually increasing to 30-40 minutes as tolerated.
- Type: Emphasize aquatic exercises (swimming or water-based workouts) or seated upper-limb resistance training and gymnastics-based activities to reduce stress on lower joints.
- Progression: Adjust gradually based on the patient’s pain level, joint range of motion, and muscular strength. After recent joint surgery or during acute pain episodes, reduce or modify exercise accordingly.
- Precautions:
1) Avoid excessive joint loading; use appropriate orthoses or support devices for knee and hip protection.
2) Monitor cardiovascular status and muscle fatigue to prevent overtraining and excessive joint wear.
3) Seek medical advice or consult with rehabilitation professionals if significant pain or worsening deformities occur, and adjust the exercise program as needed.
This report is a reference analysis based on current imaging and clinical information. It does not replace an in-person consultation or the opinion of a qualified medical professional. If you have any concerns or if symptoms change, please seek prompt evaluation at a certified healthcare facility.
Mucopolysaccharidosis type IVB (Morquio syndrome type B)
