Which lysosomal storage disorder is characterized by accumulation of heparan sulfate and dermatan sulfate due to multiple enzyme deficiencies?

Explanation

## Mucopolysaccharidosis Type I (Hurler Syndrome) **Key Point:** Mucopolysaccharidosis type I (MPS I, Hurler syndrome) results from deficiency of **α-L-iduronidase**, leading to accumulation of heparan sulfate and dermatan sulfate in lysosomes. ### Enzyme Defect & Substrate Accumulation | Feature | Details | |---------|----------| | **Deficient Enzyme** | α-L-iduronidase | | **Accumulated Substrates** | Heparan sulfate, dermatan sulfate (glycosaminoglycans) | | **Inheritance** | Autosomal recessive | | **Onset** | Symptoms appear by 6–12 months of age | ### Clinical Features (Hurler Phenotype) 1. **Facial dysmorphism:** coarse features, broad nose, thick lips, macroglossia 2. **Skeletal abnormalities:** short stature, kyphosis, dysostosis multiplex (skeletal dysplasia) 3. **Hepatosplenomegaly:** marked organomegaly 4. **Cardiac involvement:** valve disease, cardiomyopathy 5. **Neurological:** intellectual disability, progressive developmental delay 6. **Corneal clouding:** progressive vision loss 7. **Hearing loss:** conductive and sensorineural **High-Yield:** MPS I = α-L-iduronidase deficiency → heparan & dermatan sulfate accumulation → coarse features, skeletal dysplasia, organomegaly, neurodegeneration. ### Mnemonic: **MPS I = "Hurler's Coarse Features"** - **M**ucopolysaccharidosis - **P**rogressive - **S**keletal dysplasia, **S**plenomegaly, **S**hort stature - **I** = Type I **Clinical Pearl:** Hurler syndrome (MPS I-H) is the severe form; Scheie syndrome (MPS I-S) is the attenuated form with the same enzyme deficiency but milder phenotype. Both accumulate the same substrates. [cite:Robbins 10e Ch 5]