Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Salla disease

Salla disease and infantile sialic acid storage disorder are autosomal recessive disorders caused by mutations of the gene, which encodes a lysosomal membrane transporter. Neuromuscular symptoms dominate the clinical picture.

Historical Aspects

Salla disease was first published in 1979. The description included tree mentally retarded brothers and their female cousin. It was named Salla disease after the birthplace of the patients. Laboratory studies revealed increased urinary sialic acid excretion and enlarged lysosomal vacuoles. It was soon clear that it was a new lysosomal storage disease, despite the normal function of all lysosomal enzymes.[Error: Macro 'ref' doesn't exist]

Infantile sialic acid storage disorder was first described in 1982. The symptoms are more prominent and the disease leads to early death.[Error: Macro 'ref' doesn't exist]

The gene, encoding an anion transporter, was detected in 1999. The same gene is responsible for both types of the disease.[Error: Macro 'ref' doesn't exist]

Epidemiology

Salla disease is common in north-eastern Finnland, an area approximately 100km in diameter. Sporadic cases of Salla disease are observed in other countries. They often show an intermediate phenotype with clinical signs consistent with both Salla disease and infantile sialic acid storage disorder.

Infantile free sialic acid storage disease is much less common and shows no geographic aggregation.

Clinical Findings

Pregnancy and neonatal period of Salla disease patients are unremarkable. The first symptoms appear at 6-9 month of age. They include muscular hypotonia, ataxia and ocular horizontal nystagmus, which develops into a divergent squint. Motor development is delayed as is speech. One-third of patients never walk. Although many patients learn to speak single word or short sentences during their first years of life, one-third lose speech later. The speech of the remainder is characterized by dysarthria and dysphasia. Mental retardation is also prominent symptom. The patients reach a final IQ in the range of 20 to 40. Growth retardation is observed in many patients but varies among the sibs. Facial features are coarse. Other somatic symptoms are limited there is neither enlargement of spleen and liver nor ocular findings. Salla disease patients do not show the inexorable progression of symptoms so typical in other lysosomal storage diseases. The life span is relatively long and the patients reach the age of 35 years on average.

The clinical course of infantile sialic acid storage disorder is much more severe. Already in utero a hydrops fetalis is observed in some patients. Hepatomegaly, ascites and oedema characterize the neonatal period. Later on, failure to thrive, hypotonia, spleen enlargement, hypopigmentation, skeletal changes and growth retardation become apparent. The average life span is about 10 month.

Diagnosis

Family history is only instructive if the patient descends from Finland. The isolated cases observed elsewhere have no family history. Because of elevated plasma levels, the urinary excretion of sialic acid is remarkably elevated, but this symptom is shared with other diseases of silalic acid metabolism. Molecular genetic analysis allows to narrow down the diagnosis, to offer family counselling, and to consider prenatal diagnosis.

Differentials

The symptoms of intracellular accumulation of sialic acid and increased urinary secretion are shared with sialidosis, sialuria, and galactosialidosis.

Systematic

Lysosomal storage disease
Cystinosis
Fabry disease
Infantile sialic acid storage disorder
Lysosomal acid lipase deficiency
Salla disease
SLC17A5
Wolman disease

References:

1.

Verheijen FW et al. (1999) A new gene, encoding an anion transporter, is mutated in sialic acid storage diseases.

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2.

Aula N et al. (2000) The spectrum of SLC17A5-gene mutations resulting in free sialic acid-storage diseases indicates some genotype-phenotype correlation.

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3.

Kleta R et al. (2004) Clinical, biochemical, and molecular diagnosis of a free sialic acid storage disease patient of moderate severity.

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4.

Strauss KA et al. (2005) Genome-wide SNP arrays as a diagnostic tool: clinical description, genetic mapping, and molecular characterization of Salla disease in an Old Order Mennonite population.

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5.

Biancheri R et al. (2005) Homozygosity for the p.K136E mutation in the SLC17A5 gene as cause of an Italian severe Salla disease.

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6.

Morse RP et al. (2005) Novel form of intermediate salla disease: clinical and neuroimaging features.

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7.

Tondeur M et al. (1982) Infantile form of sialic acid storage disorder: clinical, ultrastructural, and biochemical studies in two siblings.

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8.

None (2003) Sialic acid storage disease and related disorders.

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9.

None (2005) Disorders of free sialic acid.

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10.

Gopaul KP et al. (2006) The inborn errors of sialic acid metabolism and their laboratory investigation.

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11.

Aula P et al. (1979) "Salla disease": a new lysosomal storage disorder.

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12.

Orphanet article

Orphanet ID 309334 [^]
13.

OMIM.ORG article

Omim 604369 [^]
14.

Wikipedia article

Wikipedia EN (Salla_disease) [^]
Update: April 29, 2019