A 3-year-old boy from rural Maharashtra presents with progressive developmental delay, hepatosplenomegaly, and recurrent respiratory infections over the past 18 months. On examination, he has coarse facial features, corneal clouding, and a palpable spleen 4 cm below the costal margin. Bone marrow aspirate shows foamy macrophages. Urine shows elevated heparan sulfate and dermatan sulfate. Which of the following lysosomal storage disorders is most likely?

Explanation

## Diagnosis: Hurler Syndrome (MPS I) ### Clinical Presentation Match **Key Point:** Hurler syndrome is the severe form of mucopolysaccharidosis type I (MPS I), caused by deficiency of the enzyme α-L-iduronidase, leading to accumulation of heparan sulfate and dermatan sulfate. The clinical triad in this case is pathognomonic: 1. **Coarse facial features** — broad nasal bridge, thick lips, full cheeks 2. **Corneal clouding** — due to glycosaminoglycan deposition in the cornea 3. **Hepatosplenomegaly** — from macrophage infiltration and storage material accumulation ### Biochemical Findings | Feature | Hurler Syndrome | Gaucher Disease | Niemann-Pick | Fabry Disease | |---------|-----------------|-----------------|--------------|---------------| | **Enzyme defect** | α-L-iduronidase | Glucocerebrosidase | Sphingomyelinase | α-Galactosidase A | | **Substrate** | Heparan sulfate, dermatan sulfate | Glucocerebroside | Sphingomyelin | Globotriaosylceramide | | **Urine findings** | ↑ Heparan & dermatan sulfate | Normal urine | Normal urine | Normal urine | | **Corneal clouding** | Yes (early) | No | No | No | | **Coarse features** | Yes (prominent) | No | No | No | | **Foamy macrophages** | Yes | Yes | Yes | No | ### High-Yield Features of Hurler Syndrome **High-Yield:** The combination of **coarse facies + corneal clouding + elevated urinary glycosaminoglycans (GAGs)** is diagnostic of MPS I (Hurler). **Mnemonic: MPS I HURLER** — **H**eparan sulfate, **U**rinary GAGs elevated, **R**espiratory infections, **L**arge organs (hepatosplenomegaly), **E**ye (corneal clouding), **R**ough features (coarse facies) ### Clinical Pearl **Clinical Pearl:** Hurler syndrome typically presents between 6–24 months of age with developmental delay, and death usually occurs by age 10 years without treatment due to cardiopulmonary complications. Hematopoietic stem cell transplantation (HSCT) in early stages can slow progression. ### Why Urinary GAGs Are Diagnostic The **elevated heparan sulfate and dermatan sulfate in urine** is the biochemical hallmark. This occurs because: - Lysosomes cannot degrade these GAGs - They accumulate intracellularly and overflow into urine - This finding is **specific to MPS disorders** and distinguishes them from other lysosomal storage diseases [cite:Robbins 10e Ch 5]