Sanfilippo Syndrome: The Tale of a Challenging Diagnosis

Abstract Sanfilippo syndrome or mucopolysaccharidosis III (MPS III), includes a group of four autosomal recessive lysosomal storage disorders caused by deficient activity of enzymes involved in the catabolism of heparan sulfate. The four types of MPS III are recognized in accordance with the deficient enzyme, resulting in the accumulation of heparan sulfate with particularly deleterious effects in the central nervous system. The incidence of MPS III remains to be established in Latin American countries. We describe the journey of a patient with MPS IIIB whom, even in the presence of speech delay and deterioration, behavioral problems and motor incoordination, showed unaltered urinary glycosaminoglycans (GAGs) levels. An investigation for MPS was undertaken and enzyme analysis indicated a deficiency of alpha-N-acetylglucosaminidase, leading to the diagnosis of MPS IIIB. With the correct diagnosis, the patient's symptoms could be properly managed, and the parents received appropriate genetic counseling. The present case report reinforces the need of investigating MPS III in patients with language delay and/or regression, neurological impairment and behavioral alterations, even when urinary GAGs are within normal range. A definitive diagnosis ends the diagnostic journey and enables the medical team and family to provide a better care for the child.

Development of a Clinical Algorithm for the Early Diagnosis of Mucopolysaccharidosis III

Abstract Mucopolysaccharidosis III (MPS III) is a rare inherited metabolic disease primarily affecting the central nervous system, leading to developmental and/or speech regression. Early diagnosis of the disease is important to introduce appropriate management measures and to optimize therapeutic outcomes. The diagnosis of MPS III is often significantly delayed due to the rarity of the disease, the more attenuated somatic presentation compared to other MPS types, and the symptom overlap with other developmental disorders. To shorten the time to diagnosis, a list of eight early signs and symptoms was identified through an expert system approach by a global, multidisciplinary working group of 13 specialists with expertise in various aspects of MPS and developmental disorders and three parents of MPS III patients. Coarse facial features and persistent hirsutism or prominent, thick eyebrows were identified as the most important MPS III early signs. The list of eight early MPS III signs and symptoms is the first step towards the development of a clinical algorithm aiming to identify neonates and infants with MPS III before the onset of neurocognitive damage, ultimately shortening the diagnostic journey of MPS III patients.