Mucopolysaccharidosis (Hurler / Hunter) - High-Yield Viva Questions
| Question | Answer / Practical Pearls |
|---|---|
| What is the hallmark radiographic constellation of 'Dysostosis Multiplex'? | 1. Skull: Large dolichocephalic skull with thickened calvarium; J-shaped sella turcica with shallow pituitary fossa and undercut anterior clinoids. 2. Spine: Inferior anterior beaking of lumbar vertebrae (L1-L2) producing an acute angular thoracolumbar kyphosis (gibbus); odontoid peg hypoplasia. 3. Thorax: Oar-shaped (paddle-shaped) ribs with narrow posterior vertebral necks and broad spatulate anterior shafts; short horizontal clavicles. 4. Pelvis: Flared iliac wings with shallow, oblique acetabula and hypoplastic femoral heads. 5. Hands: Claw hand deformity with proximal tapering/pointing of metacarpal bases (digits 2-5) and short, bullet-shaped phalanges. |
| How do you distinguish Hurler Syndrome (MPS I) from Hunter Syndrome (MPS II) clinically and genetically? | • Inheritance: Hurler is Autosomal Recessive (IDUA gene; equal male:female ratio); Hunter is X-Linked Recessive (IDS gene; affects almost exclusively males). • Corneal Clouding: Present in Hurler syndrome (diffuse ground-glass haze due to GAG storage in stromal keratocytes); ABSOLUTELY ABSENT in Hunter syndrome (corneas remain crystal clear!). • Cutaneous Findings: Hunter syndrome displays unique ivory-colored, pebbling/papular skin lesions over the scapulae, posterior axillae, and pectoral regions. • Enzyme Defect: Hurler = Alpha-L-Iduronidase deficiency; Hunter = Iduronate-2-Sulfatase deficiency. |
| Why is general anesthesia notoriously hazardous in an MPS child? | • The Most Lethal Difficult Pediatric Airway in Medicine: 1. Massive macroglossia and hypertrophied adenotonsillar tissues. 2. GAG infiltration of vocal cords, arytenoids, and tracheal rings causing severe narrowing and dynamic tracheobronchomalacia. 3. Stiff, short neck and restricted temporomandibular joint mobility. 4. Atlantoaxial Instability with Odontoid Hypoplasia: Forceful neck extension during conventional direct laryngoscopy can cause acute subluxation, cervical cord transection, quadriplegia, and death! • Rule: Always secure the airway via video laryngoscopy or awake fiberoptic intubation with strict in-line cervical stabilization. |
| Compare Enzyme Replacement Therapy (ERT) with Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in Hurler Syndrome. | • Enzyme Replacement Therapy (Laronidase): Administered at $0.58\text{ mg/kg}$ IV once weekly. Dramatically reduces hepatosplenomegaly, decreases urinary GAGs, improves joint range of motion, and stabilizes cardiorespiratory function. Major Limitation: Laronidase CANNOT cross the blood-brain barrier; it has zero efficacy against progressive neurocognitive decline. • Allogeneic HSCT: Definitive treatment of choice for severe MPS IH (Hurler), but MUST be performed before 2 to 2.5 years of age and before DQ drops below 70. Engrafted donor monocytes cross the blood-brain barrier, become brain microglia, and secrete active enzyme taken up by neurons, preserving intellectual development. |
| Which mucopolysaccharidosis is characterized by severe skeletal dysostosis but COMPLETELY NORMAL intellect? | • Morquio Syndrome (MPS IV): - Enzyme deficiency: N-acetylgalactosamine-6-sulfatase (Type IVA) or beta-galactosidase (Type IVB). - Urinary GAG: Keratan Sulfate. - Clinical features: Severe spondyloepiphyseal dysplasia, platyspondyly (flattened vertebrae), severe short trunk dwarfism, pectus carinatum, genu valgum, corneal clouding, and odontoid hypoplasia, but INTELLECT IS COMPLETELY PRESERVED AND NORMAL! |