Dr. Sree Lekshmy, Dr. Sheela Nampoothiri, Dr. Dhanya Yashodharan, Dr. C Jayakumar
Two old male child, only child of non consanguineous parentage presented with complaints of raised chest wall which was noticed recently mother. Vitals were stable and PICCLE was normal.
Auxology:
Weight:9.5kg
Height:79cm (3rd centile)
Head circumference:49cm
Lower segment(LS)-35cm
US:LS -1.2:1
General examination showed short neck, pectus carinatum, bilateral wrist widening, hyperelastic wrists and bilateral pesplanovalgus. Xray wrist showed bullet shaped fingers. Xray chest showed oar-shaped ribs.
Xray showing bullet shaped fingers.
Paediatric cardiology seen and ECHO showed myxomatous appearance of mitral leaflet. Opthalmology evaluation done for corneal clouding was normal. WES sent showed a known homozygous mutation in GALNS gene. Family was counselled the prognosis and the need for yearly evaluation.
Discussion:
Introduction:
Morquio Syndrome, also known as mucopolysaccharidosis type IV (MPS IV), is a rare inherited lysosomal storage disorder caused the deficiency of specific enzymes, namely N-acetylgalactosamine-6-sulfatase (GALNS) or beta-galactosidase (GLB1).
Inheritance: Autosomal recessive inheritance pattern,Mutations in the GALNS gene result in Morquio syndrome type A, while mutations in the GLB1 gene cause type B.
Pathophysiology:
The enzymes are crucial for breaking down glycosaminoglycans (GAGs), such as keratan sulfate and chondroitin-6-sulfate. The lack of enzyme activity leads to the accumulation of GAGs in cells, tissues, and organs, causing progressive damage. The excessive storage of GAGs disrupts cellular functions, especially in connective tissues, leading to skeletal deformities and systemic manifestations.
Clinical Features:
• Short stature
• Skeletal abnormalities -dwarfism, kyphosis, and pectus carinatum, genu valgum, platyspondyly (flattened vertebra), odontoid hypoplasia (increasing risk of atlanto axial instability).
• Joint hypermobility or stiffness.
• Respiratory complications due to abnormal tracheal and thoracic development.
• Cardiac: valvular heart disease such as mitral or aortic valve insufficiency.
• Dental anomalies and corneal clouding.
• Normal cognitive function, distinguishing it from other MPS disorders.
Diagnosis :
• Enzyme activity assays to confirm the deficiency.
• Genetic testing for GALNS or GLB1 mutations.
• Radiographic imaging:
– Platyspondyly: Flattened vertebral bodies with anterior beaking.
-Kyphoscoliosis
-Thoracolumbar gibbus: Sharp angulation of the thoracolumbar spine.
-Flared iliac wings: Wide and flared appearance of the pelvic bones.
-Acetabular dysplasia: Shallow acetabular sockets.
-Coxa valga: Increased femoral neck-shaft angle.
-Erlenmeyer flask deformity: Flared metaphyses, particularly in the distal femur.
-Bullet-shaped metacarpals: Short, thickened metacarpals with proximal tapering.
Treatment:
• Enzyme Replacement Therapy (ERT) with elosulfase alfa for type A.
• Supportive care, including physical therapy, orthopedic surgery, and respiratory management.
• Emerging therapies like gene therapy and substrate reduction therapy are under investigation.