Infantile free sialic acid storage disease

Infantile Free Sialic Acid Storage Disease (ISSD) is a rare lysosomal storage disorder characterized by the accumulation of free sialic acid in lysosomes. It is caused by mutations in the SLC17A5 gene, which encodes the sialin transporter responsible for transporting sialic acid out of lysosomes. This condition is part of a spectrum of disorders that also includes Salla disease, with ISSD being the more severe form.

Symptoms and Diagnosis

The symptoms of ISSD typically manifest shortly after birth and can include severe developmental delay, hypotonia (reduced muscle tone), failure to thrive, and distinctive facial features. Other symptoms may include hepatosplenomegaly (enlargement of the liver and spleen), seizures, and dysostosis multiplex, which refers to multiple skeletal abnormalities seen on X-rays.

Diagnosis of ISSD is based on clinical presentation and is confirmed through genetic testing identifying mutations in the SLC17A5 gene. Additionally, elevated levels of free sialic acid in urine can suggest the diagnosis, which can then be confirmed by enzyme assays or molecular genetic testing.

Genetics

ISSD is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disease. Parents of an individual with ISSD are typically carriers of the disease, each possessing one copy of the mutated gene.

Treatment

There is currently no cure for ISSD, and treatment is supportive and symptomatic. Management may include physical therapy to improve muscle tone and mobility, nutritional support to address failure to thrive, and medications to control seizures. Due to the progressive nature of the disease, individuals with ISSD may require multidisciplinary care from a team of specialists, including neurologists, cardiologists, and gastroenterologists, to manage the complex symptoms associated with the disorder.

Prognosis

The prognosis for individuals with ISSD is generally poor, with most affected children experiencing significant developmental delays and complications from organ enlargement and skeletal abnormalities. The lifespan of individuals with ISSD is significantly shortened, with many not surviving past early childhood.

Research

Research into ISSD and other lysosomal storage disorders is ongoing, with efforts focused on understanding the molecular mechanisms underlying these diseases and developing effective treatments. Gene therapy and enzyme replacement therapy are areas of particular interest, offering potential avenues for future therapeutic interventions.

NIH genetic and rare disease info

• NIH info on Infantile free sialic acid storage disease

Infantile free sialic acid storage disease is a rare disease.