mucopolysaccharidosis type 3C

Mucopolysaccharidosis type 3C (MPS III C), also called Sanfilippo syndrome type C, is an uncommon lysosomal storage condition that mainly affects the brain and can involve several other body systems. It results from markedly reduced activity of the enzyme acetyl-CoA:alpha-glucosaminide acetyltransferase because of variants in the HGSNAT gene. The enzyme deficiency leads to progressive difficulties with behavior, sleep, and development. The disorder is inherited in an autosomal recessive pattern and is estimated to affect roughly 1 to 9 out of every 100 000 people worldwide. Severity and symptoms vary widely between individuals.

Early signs most families notice are behavioral changes such as hyperactivity or impulsivity, sleep disturbance that may include frequent nighttime waking, and delays in reaching developmental milestones. As children grow, neurological features become more obvious; many experience intellectual disability and, in a number of cases, gradual loss of speech and other previously learned skills. Motor function can also decline over time, leading to difficulties with coordination and walking. Outside the nervous system, some individuals develop coarse facial features or excess body hair, and a subset experience hearing impairment. Skeletal and organ findings such as joint stiffness, kyphoscoliosis, hepatomegaly, or splenomegaly occur less commonly but illustrate the multi-system nature of the condition. Not all individuals experience all features, and severity varies considerably. Supportive services such as special education, speech therapy, and behavioral interventions can make a meaningful difference in day-to-day life.

MPS III C is caused by pathogenic variants in the HGSNAT gene, which provides instructions for producing the enzyme acetyl-CoA:alpha-glucosaminide acetyltransferase. When both copies of HGSNAT are altered, enzyme activity drops dramatically and cellular waste products build up in lysosomes, contributing to the symptoms described above. The disorder is inherited in an autosomal recessive manner, meaning an affected child receives one altered copy of the gene from each parent. Parents who each carry a single non-working copy (carriers) are typically healthy but have a 25 percent chance with every pregnancy of having an affected child, a 50 percent chance of having a carrier child, and a 25 percent chance of having an unaffected, non-carrier child. Because very rare variants can be shared in extended families, the condition may be more common when parents share a common ancestor. Genetic counseling is recommended for relatives who wish to understand their carrier status or discuss family-planning options.

Currently, management focuses on supportive care and symptom management. Care is typically coordinated by a multidisciplinary team that may include neurology, genetics, rehabilitation, gastroenterology, and behavioral specialists. Long-term management includes regular surveillance for potential complications; for example, routine assessments of hearing, mobility, and liver or spleen size help detect problems early when intervention is most effective. Therapies such as physical and occupational therapy aim to preserve mobility and daily living skills, while speech and behavioral therapies address communication challenges and cognitive needs. Families are encouraged to maintain close monitoring with their healthcare team to adapt interventions as needs change over time, and genetic counseling provides guidance for family planning and emerging treatment options.

The clinical course of MPS III C is progressive but highly variable, influenced by the degree of enzyme deficiency, age at diagnosis, and access to specialized care. Many children experience gradual cognitive and motor decline, yet supportive therapies and attentive monitoring can help maintain quality of life and functional abilities for longer periods. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with clinicians and support groups familiar with the condition to stay informed about care strategies and research opportunities.

Clinical trials are underway exploring new treatment approaches for MPS III C. Individuals interested in research participation can search ClinicalTrials.gov or discuss eligibility with their healthcare team.