Makindo Medical Notes

📖 Overview

• 🧬 Lysosomal storage diseases (LSDs) = inherited metabolic disorders caused by defective lysosomal enzymes.
• 🧪 Enzyme deficiency → accumulation of substrates → cell & organ damage.
• 👨‍👩‍👧 Most follow an autosomal recessive pattern (25% risk if both parents carriers).
• 🌍 Higher prevalence in certain groups (e.g., Ashkenazi Jewish population with genetic screening).

🧾 Major Types

🔎 Diagnosis

• 📜 Family history + genetic counselling.
• 🩺 Clinical assessment of symptoms & progression.
• 🧪 Enzyme assays to measure activity.
• 🧬 Genetic testing for mutations.
• 🖼️ Imaging (MRI/CT) for organ involvement.

💊 Treatment & Management

• Enzyme Replacement Therapy (ERT) 💉 → restores deficient enzyme (Gaucher, Fabry, Pompe).
• Substrate Reduction Therapy (SRT) ⚖️ → decreases substrate production.
• Hematopoietic Stem Cell Transplantation (HSCT) 🧫 → donor marrow produces functional enzymes (e.g., MPS).
• Supportive Care 🤲 → pain control, physio, nutritional support, cardiac/respiratory management.
• Gene Therapy 🧬✨ → experimental but promising in trials.

📌 Summary

• LSDs = inherited enzyme deficiencies → lysosomal substrate accumulation.
• ⚠️ Early recognition improves quality of life & prevents irreversible organ damage.
• ERT is cornerstone; SRT, HSCT, & gene therapy are evolving options.
• 🚀 Research continues to expand treatments & improve outcomes.

Cases — Lysosomal Storage Diseases

• Case 1 — Gaucher disease (Glucocerebrosidase deficiency) 🦴: A 6-year-old Ashkenazi Jewish boy presents with hepatosplenomegaly, easy bruising, anaemia, and bone pain. Bloods: pancytopenia. Bone marrow: “crumpled tissue paper” macrophages. Diagnosis: Type 1 Gaucher disease. Managed with enzyme replacement therapy (imiglucerase).
• Case 2 — Tay–Sachs disease (Hexosaminidase A deficiency) 👁️: A 9-month-old girl presents with developmental regression, hypotonia, exaggerated startle reflex, and seizures. Ophthalmoscopy: cherry-red spot at macula. Family history: Ashkenazi descent. Diagnosis: Tay–Sachs disease. No curative treatment; supportive and palliative care provided.
• Case 3 — Hurler syndrome (Mucopolysaccharidosis type I, α-L-iduronidase deficiency) 🧬: A 3-year-old boy presents with coarse facial features, corneal clouding, recurrent ear infections, hepatosplenomegaly, and developmental delay. Radiographs: dysostosis multiplex. Diagnosis: Hurler syndrome. Managed with enzyme replacement therapy and haematopoietic stem cell transplantation in selected cases.

Teaching Point 🩺: Lysosomal storage diseases are inherited metabolic disorders caused by enzyme deficiencies → accumulation of unmetabolised substrates. Key examples: - Gaucher: bone pain, cytopenias, hepatosplenomegaly. - Tay–Sachs: neurodegeneration, cherry-red spot. - Hurler: coarse facies, corneal clouding, skeletal deformities. Diagnosis: enzyme assay, genetic testing. Management: enzyme replacement, HSCT, supportive therapies. Prognosis varies by subtype.