What are GNPTAB-related Disorders?

GNPTAB-related disorders are inherited, lysosomal storage disorders caused by harmful genetic changes (mutations) 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 fall between mucolipidosis II and mucolipidosis III alpha/beta.

Mucolipidosis II

Mucolipidosis II presents at birth with skeletal problems that can include internally rotated feet (clubfeet), spinal problems, dislocated hips, abnormal rib cages, 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 affected children will have slower growth by age three, and affected individuals will usually be shorter than their unaffected family members. Affected children progressively develop coarse facial features. Heart problems are also very common. Individuals with mucolipidosis III alpha/beta are typically able to walk, though due to joint stiffening, may need to use a wheelchair by early adulthood. Intelligence and language development are typically 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 Portugal or Quebec.

How are GNPTAB-related Disorders treated?

There is no cure for mucolipidosis II or III alpha/beta. Management of symptoms may include occupational therapy, speech therapy, and low-impact physical therapy. Dental management and hearing rehabilitation may be beneficial, but surgeries should be avoided in order to prevent airway complications and adverse reactions to anesthesia. Hip replacement has been helpful for some individuals with a milder disease course. For patients with mucolipidosis III alpha/beta, intravenous pamidronate may provide relief from bone density loss, joint pain, and immobility, 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 major 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.

Other names for
GNPTAB-related disorders

  • I-cell disease
  • Mucolipidosis II
  • Mucolipidosis III alpha/beta
  • Mucolipidosis IIIA
  • Pseudo-Hurler polydystrophy


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