Lysosomal Storage Disorders: Model Clinical Case and Viva Q&A

Clinical Case: Lysosomal Storage Disorder in a Child

Case Presentation: Hurler Syndrome (MPS I)

A 2-year-old boy, Jacob, is brought to the pediatric clinic by his parents with concerns about developmental delays and unusual facial features. His parents report the following:

• Progressive coarsening of facial features over the past year
• Recurrent upper respiratory infections
• Increasing difficulty in breathing, especially at night
• Delayed speech development and loss of previously acquired words
• Stiffness in joints, particularly in hands
• Umbilical and inguinal hernias

Physical Examination:

• Height and weight below the 3rd percentile
• Coarse facial features with a prominent forehead, flat nasal bridge, and thick lips
• Macrocephaly
• Corneal clouding
• Hepatosplenomegaly
• Limited range of motion in multiple joints
• Thoracolumbar gibbus deformity

Diagnostic Workup:

• Urinary glycosaminoglycan (GAG) levels: Elevated
• Enzyme assay: Deficiency of α-L-iduronidase enzyme activity in leukocytes
• Genetic testing: Pathogenic variants in the IDUA gene confirmed
• Skeletal survey: Dysostosis multiplex
• Echocardiogram: Mitral and aortic valve thickening

Diagnosis:

Based on the clinical presentation, physical examination, and diagnostic workup, Jacob is diagnosed with Mucopolysaccharidosis type I (MPS I), specifically the severe form known as Hurler syndrome.

Management Plan:

1. Initiate enzyme replacement therapy with laronidase
2. Evaluate for hematopoietic stem cell transplantation
3. Multidisciplinary care involving cardiology, neurology, ophthalmology, and orthopedics
4. Physical and occupational therapy for joint stiffness
5. Speech and language therapy
6. Genetic counseling for the family

This case highlights the importance of early recognition and diagnosis of lysosomal storage disorders, as timely intervention can significantly impact the disease course and quality of life for affected children.

Clinical Presentations of Lysosomal Storage Disorders in Children

1. Neurological Presentation

• Progressive developmental delay or regression
• Seizures (e.g., in neuronal ceroid lipofuscinoses)
• Ataxia and movement disorders (e.g., in Niemann-Pick type C)
• Cognitive decline and dementia-like symptoms (e.g., in some mucopolysaccharidoses)
• Peripheral neuropathy (e.g., in Fabry disease)

2. Skeletal and Connective Tissue Involvement

• Short stature and disproportionate growth
• Joint stiffness and contractures (e.g., in mucopolysaccharidoses)
• Bone pain and pathological fractures (e.g., in Gaucher disease)
• Spinal cord compression due to vertebral abnormalities
• Carpal tunnel syndrome (e.g., in mucolipidosis II and III)

3. Cardiovascular Manifestations

• Cardiomyopathy (e.g., in Pompe disease)
• Valvular heart disease (e.g., in mucopolysaccharidoses)
• Coronary artery disease (e.g., in Fabry disease)
• Hypertension and proteinuria (e.g., in Fabry disease)

4. Ophthalmological Features

• Corneal clouding (e.g., in mucopolysaccharidoses)
• Cherry-red spot on the macula (e.g., in Tay-Sachs disease)
• Retinal degeneration (e.g., in neuronal ceroid lipofuscinoses)
• Supranuclear gaze palsy (e.g., in Niemann-Pick type C)

5. Hepatosplenomegaly and Abdominal Symptoms

• Enlarged liver and spleen (e.g., in Gaucher disease, Niemann-Pick disease)
• Abdominal distension
• Feeding difficulties and failure to thrive
• Recurrent abdominal pain

6. Respiratory Manifestations

• Recurrent respiratory infections
• Obstructive sleep apnea (e.g., in mucopolysaccharidoses)
• Restrictive lung disease due to skeletal deformities
• Pulmonary hypertension

7. Dermatological Features

• Angiokeratomas (e.g., in Fabry disease)
• Thick, waxy skin (e.g., in Hunter syndrome)
• Excessive body hair growth (e.g., in some mucopolysaccharidoses)

8. Hematological Abnormalities

• Anemia and thrombocytopenia (e.g., in Gaucher disease)
• Coagulation abnormalities
• Foam cells in bone marrow (e.g., in Niemann-Pick disease)

9. Dysmorphic Features

• Coarse facial features (e.g., in mucopolysaccharidoses)
• Macrocephaly
• Gingival hyperplasia
• Macroglossia

10. Endocrine and Metabolic Disturbances

• Growth hormone deficiency
• Hypothyroidism (e.g., in multiple sulfatase deficiency)
• Adrenal insufficiency (e.g., in X-linked adrenoleukodystrophy)
• Diabetes insipidus (e.g., in Wolfram syndrome)

Knowledge Check: Question and Answers for Medical Students & Professionals

This interactive quiz component covers essential viva questions and answers. It includes 30 high-yield viva questions with detailed answers.

Question 1 of 30

Disclaimer

The notes provided on Pediatime are generated from online resources and AI sources and have been carefully checked for accuracy. However, these notes are not intended to replace standard textbooks. They are designed to serve as a quick review and revision tool for medical students and professionals, and to aid in theory exam preparation. For comprehensive learning, please refer to recommended textbooks and guidelines.