The parents of a male infant report that male children over three generations in the mother’s family have been affected by a progressive disorder involving multiple organ systems. These children have had coarse facial features, corneal clouding, joint stiffness, hepatosplenomegaly, and mental retardation, and many died in childhood. At autopsy, some of the children had subendothelial coronary arterial deposits that caused myocardial infarction. Laboratory testing of the infant now shows increased urinary excretion of mucopolysaccharides. Bone marrow biopsy is performed, and the accumulated mucopolysaccharides are found in macrophages (“balloon cells” filled with minute vacuoles). Which of the following enzyme deficiencies is most likely to be seen in this infant?

**Core Concept**
The question describes a genetic disorder characterized by the accumulation of mucopolysaccharides, leading to a range of systemic symptoms and organ damage. This condition is a type of lysosomal storage disorder, which results from the deficiency of a specific enzyme responsible for breaking down complex carbohydrates.

**Why the Correct Answer is Right**
The infant's symptoms, including coarse facial features, corneal clouding, joint stiffness, hepatosplenomegaly, and mental retardation, are consistent with Hurler syndrome, a type of mucopolysaccharidosis (MPS). The increased urinary excretion of mucopolysaccharides and the presence of "balloon cells" in the bone marrow biopsy are also characteristic of this condition. The enzyme deficiency responsible for Hurler syndrome is alpha-L-iduronidase, which is necessary for the breakdown of dermatan sulfate and heparan sulfate, two types of mucopolysaccharides. The accumulation of these substances in lysosomes leads to cellular dysfunction and the characteristic clinical features of the disease.

**Why Each Wrong Option is Incorrect**
**Option A:** The question is not asking about alpha-galactosidase A deficiency, which is responsible for Fabry disease, a different type of lysosomal storage disorder.
**Option B:** The question is not asking about iduronate-2-sulfatase deficiency, which is responsible for Hunter syndrome, a different type of mucopolysaccharidosis that primarily affects males.
**Option C:** The question is not asking about beta-glucuronidase deficiency, which is responsible for Sly syndrome, a type of mucopolysaccharidosis that primarily affects the bones and joints.
**Option D:** The question is not asking about hexosaminidase A deficiency, which is responsible for Tay-Sachs disease, a different type of lysosomal storage disorder that primarily affects the nervous system.

**Clinical Pearl / High-Yield Fact**
Hurler syndrome is caused by a deficiency of alpha-L-iduronidase, an enzyme necessary for the breakdown of dermatan sulfate and heparan sulfate. This condition is inherited in an autosomal recessive pattern and is characterized by a range of systemic symptoms, including coarse facial features, corneal clouding, joint stiffness, hepatosplenomegaly, and mental retardation.

**Correct Answer:** A. Alpha-L-iduronidase deficiency.

✓ Correct Answer: B. a-l-Iduronidase