Mucolipidosis II

Mucolipidosis II (ML II), sometimes also referred to as I-cell disease, is a progressively debilitating inherited disorder caused by the accumulation of products throughout the body that are supposed to be broken apart. This is due to a deficient enzyme called G1cNAc-1-phosphotransferase. Affected infants are typically born with several bone abnormalities and most never learn how to walk independently because they have severe joint deformities as well. A few of these skeletal abnormalities can be seen prenatally by ultrasound. They have slow growth through the first year of life and stop growing during the second year of life. Most affected children have heart valve problems and narrow airways that contribute to recurrent respiratory infections. They often have recurrent ear infections, as well, that lead to hearing loss. Their skin becomes thickened and their facial features develop a characteristic look often referred to as "coarse". Motor development is significantly delayed and intellect is also below normal for age. Life expectancy is short, with death typically occurring in childhood. There is no cure for ML II but medical surveillance and care may help to improve some symptoms and overall condition of life. Mucolipidosis II is caused by pathogenic variants in the GNPTAB gene.

ML II is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

There are generally no signs or symptoms associated with being a carrier for ML II. However, the risk to have a child affected with ML II is increased. Testing of reproductive partners is recommended for carriers of ML II.

It is unknown exactly how often ML II occurs, but worldwide it is estimated to affect between 1 in 100,000 to 400,000 newborns. There does appear to be an unusually high occurrence of 1 in 6184 newborns affected in a region of Quebec, Canada.

The following websites may be informative: Genetic Home Reference: Mucolipidosis II alpha/beta (http://ghr.nlm.nih.gov/)

Gene Reviews: Mucolipidosis II (http://www.ncbi.nlm.nih.gov/books/NBK1116/) OMIM: [252500: MUCOLIPIDOSIS II ALPHA/BETA] (http://www.ncbi.nlm.nih.gov/omim)

• Full gene sequencing