Know Your Disease: Mucolipidosis II (I-Cell disease) Disease
What is Mucolipidosis II (I-Cell disease)?
Mucolipidosis II (also known as I-cell disease) is a progressively debilitating disorder that affects many parts of the body. Most affected individuals do not survive past early childhood. Mucolipidosis type III (Pseudohurler polydystrophy) is a milder variant of this disease.
What are the symptoms of I-Cell disease?
Coarse facial features
Congenital hip dislocation
Joint stiffness and claw hand deformities
Lumbar gibbus deformity and kyphoscoliosis
· Abdomen: Umbilical and inguinal hernias, Diastasis recti, Mild hepatomegaly
· Cardiovascular findings: Aortic insufficiency murmur may be present
· Ophthalmologic findings: Corneas may be clear or hazy.
· Neurologic findings: Generalized hypotonia may be observed.
How common is the disease?
Mucolipidosis II alpha/beta is a rare disorder, although its exact prevalence is unknown. It is estimated to occur in about 1 in 100,000 to 400,000
What genes are related to I-Cell disease?
GNPTAB gene provides instructions for making part of an enzyme called GlcNAc-1-phosphotransferase. Mutations in the GNPTAB gene that cause
mucolipidosis II alpha/beta prevent the production of any functional GlcNAc-1-phosphotransferase. Without this enzyme, digestive enzymes cannot be tagged
with M6P and transported to lysosomes. Instead, they end up outside the cell and have increased digestive activity. The lack of digestive enzymes within
lysosomes causes large molecules to accumulate there. Mutations in GNPTG lead to milder Mucolipidosis Type III.
I-Cell disease is diagnosed based on thorough clinical evaluation, identification of characteristic symptoms, detailed patient history.
UDP-N-acetylglucoseamine-1-phosphotransferase enzyme activity can be measured in white blood cells or in cultured fibroblasts. Diagnosis can be confirmed
by molecular genetic testing detecting mutations in the GNPTAB and GNPTG gene.
Prenatal diagnosis can be performed through chorionic villus biopsy or amniocentesis, if the mutations in the family are known.