Sanfilippo Type B, also known as Mucopolysaccharidosis Type IIIB (MPS IIIB), is a rare and progressive genetic disorder that has a profound impact on affected individuals and their families. This condition belongs to a group of diseases where the body cannot properly break down certain complex sugars. The disorder leads to significant health challenges, particularly affecting neurological function over time.
Understanding Sanfilippo Type B
Sanfilippo Type B is classified as a lysosomal storage disorder, specifically one of the Mucopolysaccharidosis Type III (MPS III) subtypes. Lysosomes are compartments within cells responsible for recycling waste materials. In MPS IIIB, mutations in the NAGLU gene lead to a deficiency of the alpha-N-acetylglucosaminidase (NAGLU) enzyme.
The absence or severe deficiency of the NAGLU enzyme prevents the proper breakdown of a complex sugar molecule known as heparan sulfate. As a result, heparan sulfate accumulates within the lysosomes of cells throughout the body, causing cellular damage. This accumulation is particularly harmful to brain cells, leading to most neurological symptoms.
Signs and Progression
Signs and symptoms usually appear between ages two and six years. Early indications include developmental delays, especially in speech and motor skills. Over time, behavioral issues frequently emerge, such as hyperactivity, sleep disturbances, and sometimes aggressive or defiant behaviors.
The disease progresses, causing neurological decline and loss of acquired skills, often described as childhood dementia. Physical manifestations include coarse facial features like full lips and heavy eyebrows, and joint stiffness. Other potential symptoms can include recurrent sinus or respiratory infections, gastrointestinal problems, hearing loss, and visual impairment. The severity and age of onset can vary among individuals.
Diagnosis and Genetic Basis
Diagnosis of Sanfilippo Type B begins with clinical presentation and medical history. Initial screening tests may involve measuring glycosaminoglycan levels, specifically heparan sulfate, in urine, as elevated levels can indicate a lysosomal storage disorder. However, these are screening tests and not definitive for a specific subtype.
A definitive diagnosis uses enzyme assays to measure NAGLU enzyme activity in blood or skin cells. Genetic testing, identifying mutations in the NAGLU gene, confirms the diagnosis. Sanfilippo Type B follows an autosomal recessive inheritance pattern; an individual must inherit two copies of the mutated NAGLU gene, one from each parent, to develop the condition. Parents who each carry one copy of the mutated gene are typically unaffected but have a 25% chance with each pregnancy of having a child with Sanfilippo Type B.
Management and Research Directions
Currently, there is no cure for Sanfilippo Type B; management focuses on symptomatic and supportive care to improve quality of life. A multidisciplinary team approach addresses the challenges. Therapies are tailored to manage specific issues, such as antiepileptic medications for seizures, strategies for sleep disturbances, and nutritional support for feeding difficulties.
Physical therapy, occupational therapy, and speech therapy are often employed to help maintain mobility, daily living skills, and communication abilities as long as possible. Surgical interventions might be considered for issues like hernias or carpal tunnel syndrome, and hearing aids can address hearing loss. Genetic counseling is also recommended for families to understand the implications of the disease and discuss future reproductive options.
Research explores disease-modifying treatments. Gene therapy, which aims to introduce a functional copy of the NAGLU gene into the patient’s cells, is a focus, with clinical trials underway for MPS IIIB. Enzyme replacement therapy, which involves administering the deficient enzyme, is also being investigated. Other research directions include substrate reduction therapy, designed to reduce the production of heparan sulfate, and chaperone therapy, which helps to stabilize and improve the function of existing enzymes. These ongoing efforts offer hope for future therapeutic options.