Autosomal recessive inherited metabolic disorder characterized by hyperexcretion of free sialic acid in the urine and by its storage in the lysosomes of different tissues. It is the most severe form of the sialic acid storage diseases. Clinical features include coarse facial abnormalities, clear cornea, albinoid fungi, ptosis, nystagmus, anteverted nose, high-arched palate, cardiomegaly, heart failure, hepatosplenomegaly, Nephrotic Syndrome, hypotonia, and developmental delay. Neonatal ascites, hydrops fetalis, and early death can occur.
Intermediate Salla Disease; Salla Disease; Lysosomal Free Sialic Acid Disease.
There are three different forms for this medical condition:
Sialuria: Rarest form of sialic acid storage disease. Sialuria is a rare disorder characterized by elevated levels of free sialic acid. Accumulation of sialic acid in sialuria occurs in the cytoplasm and not in the lysosomes.
Moderate Form (Salla Disease; Free Sialic Storage Disease; Sialuria Finnish Type): Adult form of sialuria mostly observed in the northeastern part of Finland. Clinical features include progressive mental and psychomotor retardation, clumsiness, onset at age 12 to 18 months with deterioration in the second decade, 4 to 15% vacuolated lymphocytes, enlarged storage lysosomes, and increased sialic acid in the urine. Ataxia, athetosis, rigidity, spasticity, impaired speech, growth retardation, thick calvaria, and exotropia are present in more than 50% of patients. Life expectancy is reduced to the seventh decade in most patients.
Severe Form: Infantile Sialic Acid Storage Disease (ISSD; Sialuria, Infantile Form; N-Acetyl-Neuraminic Acid Storage Disease; NANA Storage Disease): Usually diagnosed in the newborn period. Unlike Salla disease, there is no ethnic prevalence. Clinically, it presents with severe visceral involvement, dysostosis multiplex, psychomotor retardation, and early death.
The prevalence of this medical condition is estimated at 1 in 528,000 live births worldwide. In general, free sialic acid storage disorders affect males and females in equal numbers. The exact incidence of these disorders in the general population is unknown. Salla disease has been reported in about 150 individuals, most from Finland and Sweden. Free sialic acid storage diseases may go misdiagnosed or undiagnosed, making it difficult to determine their true frequency in the general population.
Sialuria differs from the sialidosis in the accumulation and excretion of free sialic acid in the presence of normal or increased levels of neuraminidase activity. Sialuria occurs because of defective feedback inhibition on the enzyme UDP-GlcNAc 2-epimerase in the process of NANA synthesis. Both Salla disease and infantile sialic acid storage disease are caused by impairment of an active transport system of free sialic acid across lysosomal membrane and probably are allelic to each other, despite different clinical features. Genetic mapping of both forms is assigned to 6q14-q15 on the long arm of chromosome 6.