Infantile sialic acid storage disorder

Infantile Sialic Acid Storage Disorder

Infantile Sialic Acid Storage Disorder (ISSD) is a rare, inherited metabolic disorder characterized by the accumulation of free sialic acid in tissues and urine. It is a severe form of sialic acid storage disease, which also includes Salla disease, a milder variant. ISSD is caused by mutations in the SLC17A5 gene, which encodes a sialin protein responsible for transporting sialic acid out of lysosomes.

Clinical Presentation

Infantile Sialic Acid Storage Disorder typically presents in infancy with a range of symptoms, including:

• Developmental delay: Infants with ISSD often exhibit significant delays in reaching developmental milestones.
• Hypotonia: Decreased muscle tone is common, leading to difficulties in movement and posture.
• Failure to thrive: Affected infants may have poor growth and weight gain.
• Hepatosplenomegaly: Enlargement of the liver and spleen is frequently observed.
• Coarse facial features: Distinctive facial features may develop over time.
• Neurological impairment: Seizures, ataxia, and other neurological issues are common.

Pathophysiology

The underlying cause of ISSD is a defect in the SLC17A5 gene, which leads to a dysfunctional sialin protein. This protein is crucial for the transport of sialic acid from lysosomes to the cytoplasm. When sialin is non-functional, sialic acid accumulates within lysosomes, disrupting normal cellular function and leading to the symptoms observed in ISSD.

Diagnosis

Diagnosis of ISSD involves a combination of clinical evaluation, biochemical testing, and genetic analysis:

• Urine analysis: Elevated levels of free sialic acid in the urine are indicative of the disorder.
• Genetic testing: Identification of mutations in the SLC17A5 gene confirms the diagnosis.
• Imaging studies: MRI and other imaging techniques may reveal characteristic changes in the brain and other organs.

Treatment

Currently, there is no cure for Infantile Sialic Acid Storage Disorder. Treatment is primarily supportive and symptomatic, focusing on:

• Nutritional support: Ensuring adequate nutrition to promote growth and development.
• Physical therapy: To improve muscle tone and motor skills.
• Seizure management: Anticonvulsant medications may be used to control seizures.

Prognosis

The prognosis for infants with ISSD is generally poor, with most affected individuals not surviving beyond early childhood. The severity of symptoms and rate of progression can vary, but the disorder is typically rapidly progressive.

Also see

• Salla disease
• Lysosomal storage disease
• Metabolic disorder
• Genetic disorder