Mucopolysaccharidosis type II (MPS II), also known as Hunter syndrome, is a rare inherited genetic disorder. It occurs when the body lacks or has a deficient enzyme needed to break down specific complex sugar molecules. This deficiency results in the accumulation of these molecules within the body’s cells, leading to progressive damage in various organs and tissues. The condition primarily affects males and can lead to a range of physical and neurological complications.
Understanding the Genetic Basis
Hunter syndrome is an X-linked recessive disorder, meaning it is passed from a mother to her son. Females usually carry the gene without experiencing symptoms, while males who inherit the affected X chromosome develop the condition. This disorder specifically involves a deficiency in the enzyme iduronate-2-sulfatase (IDS), which is encoded by the IDS gene located on the X chromosome.
The IDS enzyme is responsible for breaking down complex sugar molecules called glycosaminoglycans (GAGs), specifically dermatan sulfate and heparan sulfate. Without sufficient IDS activity, these GAGs accumulate within the lysosomes, cellular compartments responsible for waste breakdown and recycling. This buildup causes cellular dysfunction and damage.
Over 600 different types of mutations in the IDS gene have been identified, including point mutations, frameshift mutations, insertions, and deletions. These genetic variations contribute to the wide spectrum of disease severity observed in individuals with Hunter syndrome.
Recognizing the Physical and Developmental Signs
Symptoms of Hunter syndrome are not present at birth but often appear in young children, between ages 2 and 4. The severity and progression of symptoms vary significantly, classified into attenuated (milder) and severe forms. Attenuated forms progress more slowly with less pronounced symptoms, while severe forms involve rapid progression and broader systemic involvement.
Physical manifestations include distinctive facial features, such as thickened lips, a broad nose, and an enlarged tongue. Children may also develop an enlarged head (macrocephaly) and a short neck. Other common signs include joint stiffness and skeletal abnormalities known as dysostosis multiplex.
GAG accumulation can affect many internal organs, leading to an enlarged liver and spleen (hepatosplenomegaly) and a distended abdomen. Thickened airway tissues also cause respiratory issues, including frequent upper respiratory infections, enlarged tonsils and adenoids, and obstructive sleep apnea. Heart valve problems are a concern, potentially leading to an enlarged heart and heart failure.
In severe forms of Hunter syndrome, neurological involvement is prominent. Children may experience developmental delays, cognitive decline, behavioral changes, and speech delays. Hearing loss is also a common symptom. Some individuals may develop carpal tunnel syndrome and hydrocephalus.
Diagnosis and Current Treatment Options
Diagnosing Hunter syndrome begins with physician suspicion based on the child’s physical signs and symptoms. Initial screening tests may include urine analysis for elevated GAG levels. While suggestive, a definitive diagnosis requires further testing.
Enzyme assays are the most conclusive diagnostic step, measuring the activity of the iduronate-2-sulfatase (IDS) enzyme in blood, skin cells, or other tissue samples. A reduced or absent IDS enzyme activity confirms the deficiency. Genetic testing can then identify specific mutations in the IDS gene.
Current treatment for Hunter syndrome focuses on managing symptoms and slowing disease progression, as there is no cure. Enzyme replacement therapy (ERT) is a common approach, involving the intravenous administration of a human-made IDS enzyme, such as idursulfase (Elaprase®). This therapy helps break down accumulated GAGs in many parts of the body.
While ERT can be effective in addressing many physical symptoms and improving organ function, its ability to cross the blood-brain barrier is limited, meaning it may have less impact on neurological symptoms and cognitive decline. Treatment plans for Hunter syndrome are tailored to the individual patient and involve a multidisciplinary team of specialists.