mucopolysaccharidosis type 2

Mucopolysaccharidosis type 2 is a lysosomal storage disease characterized by a massive accumulation of glycosaminoglycans, leading to multisystem involvement including distinctive facial features, short stature, skeletal abnormalities, and cardio-respiratory issues. The condition arises from pathogenic variants in the IDS gene, which result in decreased activity of the enzyme iduronate-2-sulfatase. As an X-linked disorder, it primarily affects males, while female carriers may exhibit mild symptoms due to variable X-inactivation. This condition is rare, affecting approximately 1 to 9 people per million.

The clinical presentation of mucopolysaccharidosis type 2 includes several characteristic findings. Almost all affected individuals exhibit splenomegaly, elevated urinary glycosaminoglycan excretion, decreased iduronate sulfatase levels, a thick lower lip vermilion, and hepatomegaly. Many patients also develop macrocephaly, coarse facial features, and hepatosplenomegaly, while a subset experience skeletal abnormalities such as dysostosis multiplex, flexion contractures, and short stature. In addition, some individuals may show signs of neurodegeneration, sleep apnea, airway obstruction, and hearing impairment. Not all individuals experience all features, and severity varies considerably.

Mucopolysaccharidosis type 2 is caused by pathogenic variants in the IDS gene, which encodes the lysosomal enzyme iduronate-2-sulfatase. Disruption of this enzyme’s function leads to the accumulation of glycosaminoglycans in various tissues, contributing to the multisystem manifestations of the disease. The condition is inherited in an X-linked recessive pattern, meaning it predominantly affects males, while female carriers may experience mild symptoms due to variable X-inactivation. Genetic counseling is recommended for affected families to discuss implications for family planning.

Currently, management of mucopolysaccharidosis type 2 focuses on supportive care and symptom management, as there are no treatments specifically approved for this condition. Treatment is tailored to the individual and typically involves a multidisciplinary team, with an emphasis on regular surveillance to detect emerging complications and manage them before they become severe. In the absence of specific foundational or targeted therapies, routine monitoring—such as cardiac evaluations, pulmonary assessments, and orthopedic as well as ophthalmologic evaluations—plays a key role in long-term care. Patients and their families are encouraged to discuss treatment options and supportive care measures with their healthcare team, and genetic counseling is advised to help navigate the implications of this X-linked disorder.

The long-term outlook for individuals with mucopolysaccharidosis type 2 is highly variable, with outcomes ranging from a relatively stable course in attenuated forms to more complex challenges in severe cases. Advances in supportive care and regular multidisciplinary surveillance have contributed to improved quality of life and may help delay complications associated with this condition. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition and to seek guidance from genetic counselors regarding ongoing management and family planning.

Mucopolysaccharidosis type 2 is an active research area with numerous ongoing clinical trials exploring new treatment approaches. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.