Sanfilippo syndrome, also known as mucopolysaccharidosis type III (MPS III), is a rare, inherited genetic disorder affecting the central nervous system. This condition arises when the body cannot properly break down large sugar molecules called glycosaminoglycans (GAGs), specifically heparan sulfate. The accumulation of these molecules inside cells leads to damage in various organ systems. Early diagnosis is important for managing symptoms, understanding disease progression, and exploring potential treatment options or clinical trials.
Identifying Initial Symptoms
Sanfilippo syndrome often presents with symptoms not immediately specific to the condition, making early recognition challenging. Children typically appear healthy at birth, with initial signs emerging between one and six years of age.
One common early indicator is developmental delay, particularly in speech and language acquisition. Parents might observe a slowing or loss of previously acquired skills, often between ages one and three.
Behavioral changes are also frequently reported, including hyperactivity, aggression, and sleep disturbances, appearing around three to ten years of age. These behavioral issues can sometimes be mistaken for other conditions like autism spectrum disorder or attention-deficit/hyperactivity disorder (ADHD). Physical signs, while often milder than neurological symptoms, can include coarse facial features, excessive body hair, and a larger-than-typical head size. Recurrent ear and respiratory infections are also common.
First Steps in Testing
When Sanfilippo syndrome is suspected, healthcare providers typically begin with screening tests for a mucopolysaccharidosis (MPS) disorder. A common preliminary test involves analyzing a urine sample for elevated levels of heparan sulfate. This urine MPS screening checks for abnormal amounts of these sugar molecules.
While high heparan sulfate levels in urine suggest a possible MPS disorder, this test is a screening tool, not a definitive diagnosis. It helps narrow down possibilities and indicates the need for further investigation. False negatives can occur, so a normal result does not entirely rule out the condition.
Definitive Diagnostic Tests
Following initial screening, definitive diagnostic tests confirm Sanfilippo syndrome and identify its specific type. The two primary methods are enzyme assay and genetic testing. These tests pinpoint the underlying metabolic defect.
Enzyme assays measure the activity of specific enzymes responsible for breaking down heparan sulfate. In Sanfilippo syndrome, a deficiency in one of four specific enzymes leads to heparan sulfate accumulation. For instance, type A is linked to a deficiency in heparan-N-sulfatase, while type B involves alpha-N-acetylglucosaminidase. These assays are typically performed on blood cells, such as leukocytes, or skin fibroblasts. Low or absent enzyme activity confirms the biochemical diagnosis.
Genetic testing involves DNA sequencing to identify mutations in the genes responsible for Sanfilippo syndrome. Four known genes are associated with the different types: SGSH for type A, NAGLU for type B, HGSNAT for type C, and GNS for type D. Identifying specific mutations provides a conclusive diagnosis and determines the precise subtype. This information helps understand disease progression and potential therapies. Genetic testing can be performed using samples from blood, saliva, or a cheek swab.
Diagnosis in Specific Situations
Diagnosis of Sanfilippo syndrome can also occur in other contexts. For families with a known history or identified genetic risk, prenatal diagnosis is an option. This involves testing the fetus before birth, typically through amniocentesis or chorionic villus sampling (CVS). These tests allow for genetic analysis of fetal cells to detect the syndrome.
Newborn screening programs are emerging in some regions for lysosomal storage disorders, which include Sanfilippo syndrome. While not universally available, these screenings aim to diagnose the condition before symptoms appear, offering the possibility of earlier intervention.
Differential diagnosis is important, as Sanfilippo syndrome symptoms can overlap with other neurodevelopmental disorders, such as autism or ADHD. Specialized testing, including enzyme assays and genetic analysis, is essential to differentiate Sanfilippo syndrome from these conditions and ensure an accurate diagnosis. This approach helps prevent misdiagnosis and guides appropriate care.