Sanfilippo syndrome (MPS III) is a rare genetic disorder. It is a lysosomal storage disease where the body cannot break down heparan sulfate, a complex sugar molecule. This accumulation damages cells, especially in the central nervous system. The condition’s progressive nature and non-specific early symptoms make timely diagnosis challenging.
Recognizing Early Signs
Children with Sanfilippo syndrome typically appear healthy at birth, with symptoms usually emerging between one and four years of age. Early indicators can be subtle and are often mistaken for more common childhood conditions.
Developmental delays frequently manifest, particularly in speech and cognitive abilities. A child might experience a slowing in learning new things or a regression in previously acquired skills.
Behavioral changes are also common early signs, including hyperactivity, restlessness, and sleep disturbances, which can be particularly challenging for families. Children may also exhibit temper tantrums, aggressive or destructive behaviors, or a lack of fear of danger.
Subtle physical features can also appear, such as coarse facial features, prominent eyebrows, a larger-than-typical head size (macrocephaly), and excessive body hair (hirsutism). Recurrent ear infections, chronic nasal congestion, and joint stiffness are other early signs.
The Diagnostic Process
Diagnosis typically begins when clinical suspicion arises from a child’s observed symptoms. A comprehensive medical history and physical examination are initial steps.
The first laboratory test often involves a urine sample to screen for elevated levels of glycosaminoglycans (GAGs), specifically heparan sulfate. While a positive urine test can indicate a mucopolysaccharidosis, it is not specific to Sanfilippo syndrome and requires further confirmation.
Following a positive urine screening, enzyme assays measure specific enzyme activity in blood samples or cultured skin fibroblasts. A deficiency in one of the four enzymes responsible for breaking down heparan sulfate confirms the diagnosis and identifies the specific subtype (A, B, C, or D).
Genetic testing provides definitive confirmation by identifying mutations in relevant genes, such as SGSH, NAGLU, HGSNAT, or GNS. This molecular analysis pinpoints the exact genetic alteration.
Typical Age of Diagnosis and Contributing Factors
The average age of Sanfilippo syndrome diagnosis often falls between two and six years, though this can vary significantly depending on the subtype and individual symptom progression.
For instance, the more severe types, A and B, might be diagnosed earlier, typically between 3.5 and 4.9 years, while types C and D can have a later diagnosis, sometimes ranging from 4.5 to 19 years. Despite the presence of symptoms in early childhood, diagnostic delays are common.
Several factors contribute to this delay. The non-specific nature of early symptoms often leads to misdiagnosis, with healthcare providers frequently attributing them to more common conditions such as general developmental delay, attention-deficit/hyperactivity disorder (ADHD), or autism spectrum disorder.
Sanfilippo syndrome is a rare disease, affecting approximately 1 in 70,000 births, which can lead to a lack of awareness among general practitioners. This limited familiarity can hinder early recognition.
The slow progression of symptoms in the early stages also contributes to diagnostic challenges, as the full spectrum of the condition may not be immediately apparent. Parents might spend years seeking answers for their child’s difficulties before a correct diagnosis is made.
Delayed diagnosis significantly impacts families, delaying access to supportive care, potential interventions, or clinical trials. Early identification is important for comprehensive management and genetic counseling.