A 3-year-old boy presents with developmental delay, coarse facial features, corneal clouding, and hepatosplenomegaly. Laboratory evaluation reveals deficient phosphorylation of mannose residues on glycoprotein enzymes destined for lysosomes in the Golgi apparatus. What is the diagnosis?

Answer and explanation

Correct answer: D. I-cell disease (Mucolipidosis type II)

  1. Step 1: Identify the biochemical lesion: lysosomal acid hydrolases normally undergo mannose-6-phosphate (M6P) tagging in the cis-Golgi apparatus catalyzed by UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosaminyl-1-phosphotransferase.
  2. Step 2: In I-cell disease (mucolipidosis II), deficiency of this phosphotransferase prevents M6P marker addition. As a result, acid hydrolases cannot bind M6P receptors and are constitutively secreted extracellularly into plasma, causing dense inclusion bodies (I-cells), coarse facial features, and severe developmental failure.
Answer
I-cell disease (Mucolipidosis type II).
Why not the others: Tay-Sachs disease is caused by deficiency of -hexosaminidase A, leading to GM2 ganglioside accumulation with cherry-red macular spots but no hepatosplenomegaly; Gaucher disease results from glucocerebrosidase deficiency with lipid-laden macrophages resembling crumpled tissue paper; Pompe disease is caused by lysosomal -1,4-glucosidase deficiency leading to severe hypertrophic cardiomyopathy and hypotonia.

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