GNPTAB-related disorders Carrier Screening (Genetic Testing) Overview

What are GNPTAB-related Disorders?

GNPTAB-related disorders are inherited, lysosomal storage disorders caused by harmful genetic changes (variants) in the GNPTAB gene. There are two specific forms of GNPTAB-related disorders, mucolipidosis II and mucolipidosis III alpha/beta. The symptoms associated with GNPTAB-related disorders are caused by a buildup of harmful substances in the cells of the body. While the symptoms of both conditions are similar, mucolipidosis II is the more severe form of the disease. There have been patients described with intermediate forms of disease that have symptoms of both mucolipidosis II and mucolipidosis III alpha/beta.

Mucolipidosis II

Mucolipidosis II presents at birth with skeletal problems that can include internally rotated feet (clubfeet), abnormal spine and rib cage, dislocated hips, and abnormal long bones. Infants are typically smaller than average and have very slow growth. Babies develop enlarged (coarse) facial features and thick gums in early infancy, which become more prominent with age. Most affected children will have joint stiffening, hernias, a small head and incomplete brain development (microcephaly), and severe learning difficulties. All affected individuals have heart abnormalities, and over time, all affected individuals develop difficulty in breathing (respiratory insufficiency). Infants with mucolipidosis II do not tend to meet any developmental milestones.

Mucolipidosis III Alpha/Beta

Mucolipidosis III alpha/beta typically does not present until late infancy or early childhood. Most children with the condition will have slower growth by age three, and are usually shorter than their unaffected family members. Children will develop coarse facial features over time. Heart problems are also very common. Individuals with mucolipidosis III alpha/beta are typically able to walk, though due to joint stiffening, they may need to use a wheelchair by early adulthood. Intelligence and language development are generally normal, though many affected individuals still require special education due to physical limitations. Motor development is variable and may be normal or moderately delayed.

How common are GNPTAB-related Disorders?

Mucolipidosis II and mucolipidosis III alpha/beta affect approximately 1 in 160,000 individuals worldwide but may be more common in individuals from Quebec.

How are GNPTAB-related Disorders treated?

There is no cure for mucolipidosis II or III alpha/beta, and treatment is targeted at managing symptoms. Treatment may include occupational therapy, speech therapy, and low-impact physical therapy. Dental care and hearing support can be beneficial, but surgeries should be avoided to prevent airway complications and adverse reactions to anesthesia. Hip replacement has been helpful for some individuals with a milder form of the disease. For patients with mucolipidosis III alpha/beta, a medication called pamidronate, given through an IV, may help with bone density, joint pain, and movement, but it is not a cure.

What is the prognosis for an individual with a GNPTAB-related Disorder?

The prognosis for an individual with mucolipidosis II is poor, and death usually occurs in early childhood. Heart abnormalities and respiratory insufficiency are the primary causes of death. Mucolipidosis III alpha/beta is more variable, and many affected individuals can survive into early or middle adulthood; however, exact life expectancy is unknown.

Benefits of GNPTAB-related disorders Carrier Screening (Genetic Testing)

Carrier screening is an important form of genetic testing for those who may be at risk of passing gnptab-related disorders to their baby. Carrier Screening for gnptab-related disorders can help in identifying that risk. The Foresight^® Carrier Screen helps clinicians guide care and empowers patients to take action to make the best decision for their families. Learn more about the Foresight^® Carrier Screen} by Myriad Genetics.