I-Cell Disease Flashcards
A 15-month-old boy is brought to the clinic due to developmental delay and failure to thrive. On examination, he has corneal clouding, coarse facial features, gingival hyperplasia, and restricted joint movements. Radiographs reveal skeletal abnormalities, including dysostosis multiplex. Laboratory studies show elevated lysosomal enzymes in the serum.
Which of the following is the most likely underlying pathophysiological defect?
A) Deficiency of α-L-iduronidase
B) Defective mannose-6-phosphate tagging of lysosomal enzymes
C) Deficiency of iduronate-2-sulfatase
D) Deficiency of sphingomyelinase
E) Deficiency of glucocerebrosidase
Answer: Defective mannose-6-phosphate tagging of lysosomal enzymes
Explanation: I-Cell Disease (Mucolipidosis type II) is caused by a defect in the enzyme responsible for adding mannose-6-phosphate to lysosomal enzymes in the Golgi apparatus. Without this tag, enzymes are not directed to lysosomes and are instead secreted into the extracellular space, resulting in elevated lysosomal enzymes in the serum. Clinical features include developmental delay, failure to thrive, coarse facial features, skeletal abnormalities (dysostosis multiplex), and joint restriction.
Incorrect Answers:
A) Deficiency of α-L-iduronidase causes Hurler Syndrome, which shares some features (e.g., developmental delay, coarse features) but does not involve elevated serum lysosomal enzymes.
C) Deficiency of iduronate-2-sulfatase causes Hunter Syndrome, an X-linked condition with similar features but normal lysosomal enzyme trafficking.
D) Deficiency of sphingomyelinase causes Niemann-Pick disease, which presents with hepatosplenomegaly, neurodegeneration, and a cherry-red macula but not elevated lysosomal enzymes in the serum.
E) Deficiency of glucocerebrosidase causes Gaucher disease, presenting with hepatosplenomegaly, pancytopenia, and bone crises without dysostosis multiplex or coarse features.
Fill in the blank: I-Cell Disease is categorized under __________ disorders.
Mucopolysaccharidoses
What is the major pathophysiology of I-Cell disease?
I-cell disease (inclusion cell disease/mucolipidosis type II) is an inherited lysosomal storage disorder (autosomal recessive) where there is a defect in N-acetylglucosaminyl-1-phosphotransferase, leading to the failure of the Golgi to phosphorylate mannose residues to create mannose-6-phosphate on glycoproteins causing enzymes to be secreted extracellularly rather than delivered to lysosomes. These lysosomes lack their natural digestive function, so enzymes buildup undigested, and this cellular debris within the lysosomes are called inclusion bodies. Results in coarse facial features, gingival hyperplasia, corneal clouding, restricted joint movements, claw hand deformities, kyphoscoliosis. These symptoms are similar to but more severe than Hurler syndrome.
One key feature for diagnosising this disease is testing the patient’s plasma for elevated levels of lysosomal enzymes. This diagnostic step helps to distinguish I-Cell disease often fatal in childhood.
What is the primary cause of the symptoms in I-Cell Disease?
The inability to properly target lysosomal enzymes due to enzyme deficiency.
What is the role of mannose-6-phosphate in lysosomal enzyme targeting?
It is essential for the proper targeting of enzymes to lysosomes.
True or False: I-Cell Disease is a type of lysosomal storage disorder.
True
What is I-Cell Disease also known as?
Mucolipidosis II
What enzyme deficiency is primarily associated with I-Cell Disease?
N-acetylglucosamine-1-phosphotransferase
True or False: I-Cell Disease is an autosomal dominant disorder.
False
What type of inheritance pattern does I-Cell Disease follow?
Autosomal recessive
Which demographic is most commonly affected by I-Cell Disease?
Both genders equally, but more common in certain ethnic groups.
Fill in the blank: I-Cell Disease results in the accumulation of __________ in lysosomes.
Undigested substrates
What is the typical age of presentation for I-Cell Disease?
Infancy
What are the common ocular findings in I-Cell Disease?
Corneal clouding
What are the characteristic features seen in patients with I-Cell Disease?
- Coarse facial features
- Corneal clouding
- Skeletal abnormalities
- Developmental delay
