Congenital metabolic diseases or inherited metabolic diseases are a large group of disorders that result from the absence or abnormality of an enzyme or its cofactor which interrupts a metabolic pathway causing an accumulation or deficiency of a specific metabolite.
Metabolic diseases are considered rare and the majority of them have a an incidence of 1 in 100,000 births. In most cases, metabolic disorders are caused by individual mutations, deletions or other genetic changes. Nonetheless, one enzyme can be composed of multiple subunits codified by different genes and can catalyze more than one metabolic reaction. In addition, defects in different enzymes can cause a similar clinical phenotype.
The onset and severity of the disorder can be influenced by changes in nutrition, fasting, dehydration, intercurrent diseases, medicines, extenuating activity, child birth, trauma or surgery.
Within this large group of illnesses known as inherited metabolic diseases, is Salla disease, an abnormal accumulation of sialic acid in the lysosomes of distinct tissues provoked by a defect in the transporter of sialic acid (sialin) located on the lysosome membrane. This transporter is in charge of guaranteeing the movement of the free sialic acid (N-acetylneuraminic acid) out of the lysosomes.
Free sialic acid storage disease or Salla disease is an autosomal recessive lysosomal storage disease characterized by early physical impairment and mental retardation. Salla disease is one of 40 Finnish inherited diseases (It is estimated that 1 in 40 persons are carriers.) and affects approximately 130 individuals, mainly from Finland and Sweden. Its clinical manifestations are heterogeneous.
Infantile free sialic acid storage disease (ISSD) is the most severe form of this disorder and can appear in utero (with hydrops fetalis: an accumulation of fluid, or edema, in at least two fetal compartments) and ascites, or at birth (with hypotonia, hepatosplenomegaly-frequently associated with ascites, coarse facial features, bone malformations, serious motor deficiencies, intellectual disability and seizures).
Children with the severe forms of the illness usually die in early childhood. Those with less severe forms (initially described in Finland as Salla disorder) develop hypotonia during the first year of life. The disease can progress to include intellectual disability and developmental delay, seizures, problems with movement and balance (ataxia), abnormal tensing of the muscles (spasticity), and involuntary slow, sinuous movements of the limbs (athetosis). Individuals with Salla disease usually survive into adulthood but with severe mental retardation.
Free sialic acid storage disorders are inherited in an autosomal recessive manner. The gene that causes the disorder (SLC17A5) is located on chromosome 6, where several mutations have been described.
Biologically speaking, a diagnosis of the illness can be obtained from urine excretion or from free siatic acid storage in the fibroblasts, trophoblasts or amincytes. The treatment only treats the symptoms.
The accumulation of free sialic acid in the lysosomes can be expressed by three clinical phenotypes: infantile free sialic acid storage thesaurismosis, Salla disease and sialuria.