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Salla disease(SD)

MedGen UID:
203368
Concept ID:
C1096903
Disease or Syndrome
Synonyms: Free Sialic Acid Storage Disorders; Infantile sialic acid storage disorder (ISSD); N-acetylneuraminic acid (NANA) storage disease (NSD); SD; Sialuria, Finnish type
SNOMED CT: Adult sialic acid storage disease (87074006); Salla disease (87074006); Sialuria, Finnish type (87074006)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): SLC17A5 (6q13)
 
Monarch Initiative: MONDO:0011449
OMIM®: 604369
Orphanet: ORPHA309334

Disease characteristics

Excerpted from the GeneReview: Free Sialic Acid Storage Disorders
Free sialic acid storage disorders (FSASDs) are a spectrum of neurodegenerative disorders resulting from increased lysosomal storage of free sialic acid. Historically, FSASD was divided into separate allelic disorders: Salla disease, intermediate severe Salla disease, and infantile free sialic acid storage disease (ISSD). The mildest type was Salla disease, characterized by normal appearance and absence of neurologic findings at birth, followed by slowly progressive neurologic deterioration resulting in mild-to-moderate psychomotor delays, spasticity, athetosis, and epileptic seizures. Salla disease was named for a municipality in Finnish Lapland where a specific founder variant is relatively prevalent. However, the term Salla has been used in the literature to refer to less severe FSASD. More severe FSASD is historically referred to as ISSD, and is characterized by severe developmental delay, coarse facial features, hepatosplenomegaly, and cardiomegaly; death usually occurs in early childhood. [from GeneReviews]
Authors:
David Adams  |  Melissa Wasserstein   view full author information

Additional descriptions

From OMIM
Sialic acid storage diseases are autosomal recessive neurodegenerative disorders that may present as a severe infantile form (ISSD) or as a slowly progressive adult form that is prevalent in Finland (Salla disease). The main symptoms are hypotonia, cerebellar ataxia, and mental retardation; visceromegaly and coarse features are also present in the infantile cases. Progressive cerebellar atrophy and dysmyelination have been documented by MRI. Enlarged lysosomes are seen on electron microscopic studies, and patients excrete large amounts of free sialic acid in the urine (Verheijen et al., 1999).  http://www.omim.org/entry/604369
From MedlinePlus Genetics
People with intermediate severe Salla disease have signs and symptoms that fall between those of ISSD and Salla disease in severity.

Salla disease is a less severe form of sialic acid storage disease. Babies with Salla disease usually begin exhibiting hypotonia during the first year of life and go on to experience progressive neurological problems. Signs and symptoms of Salla disease 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.

Infantile free sialic acid storage disease (ISSD) is the most severe form of this disorder. Babies with this condition have severe developmental delay, weak muscle tone (hypotonia), and failure to gain weight and grow at the expected rate (failure to thrive). They may have unusual facial features that are often described as "coarse," seizures, bone malformations, an enlarged liver and spleen (hepatosplenomegaly), and an enlarged heart (cardiomegaly). The abdomen may be swollen due to the enlarged organs and an abnormal buildup of fluid in the abdominal cavity (ascites). Affected infants may have a condition called hydrops fetalis in which excess fluid accumulates in the body before birth. Children with this severe form of the condition usually live only into early childhood.

Sialic acid storage disease is an inherited disorder that primarily affects the nervous system. People with sialic acid storage disease have signs and symptoms that may vary widely in severity. This disorder is generally classified into one of three forms: infantile free sialic acid storage disease, Salla disease, and intermediate severe Salla disease.  https://medlineplus.gov/genetics/condition/sialic-acid-storage-disease

Clinical features

From HPO
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Athetosis
MedGen UID:
2115
Concept ID:
C0004158
Disease or Syndrome
A slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Athetosis involves continuous smooth movements that appear random and are not composed of recognizable sub-movements or movement fragments. In contrast to chorea, in athetosis, the same regions of the body are repeatedly involved. Athetosis may worsen with attempts at movement of posture, but athetosis can also occur at rest.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Thickened calvaria
MedGen UID:
346823
Concept ID:
C1858452
Finding
The presence of an abnormally thick calvaria.
Vacuolated lymphocytes
MedGen UID:
332307
Concept ID:
C1836855
Finding
The presence of clear, sharply defined vacuoles in the lymphocyte cytoplasm.
Abnormality of metabolism/homeostasis
MedGen UID:
867398
Concept ID:
C4021768
Finding
Exotropia
MedGen UID:
4613
Concept ID:
C0015310
Disease or Syndrome
A form of strabismus with one or both eyes deviated outward.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Salla disease in Orphanet.

Professional guidelines

PubMed

Aula N, Aula P
Prenat Diagn 2006 Aug;26(8):655-8. doi: 10.1002/pd.1431. PMID: 16715535
Aula N, Salomäki P, Timonen R, Verheijen F, Mancini G, Månsson JE, Aula P, Peltonen L
Am J Hum Genet 2000 Oct;67(4):832-40. Epub 2000 Aug 17 doi: 10.1086/303077. PMID: 10947946Free PMC Article
Schleutker J, Sistonen P, Aula P
J Med Genet 1996 Jan;33(1):36-41. doi: 10.1136/jmg.33.1.36. PMID: 8825046Free PMC Article

Recent clinical studies

Etiology

Huizing M, Hackbarth ME, Adams DR, Wasserstein M, Patterson MC, Walkley SU, Gahl WA; FSASD Consortium
Neurosci Lett 2021 Jun 11;755:135896. Epub 2021 Apr 20 doi: 10.1016/j.neulet.2021.135896. PMID: 33862140Free PMC Article
Steenweg ME, Vanderver A, Blaser S, Bizzi A, de Koning TJ, Mancini GM, van Wieringen WN, Barkhof F, Wolf NI, van der Knaap MS
Brain 2010 Oct;133(10):2971-82. doi: 10.1093/brain/awq257. PMID: 20881161Free PMC Article
Varho TT, Alajoki LE, Posti KM, Korhonen TT, Renlund MG, Nyman SR, Sillanpää ML, Aula PP
Pediatr Neurol 2002 Apr;26(4):267-73. doi: 10.1016/s0887-8994(01)00406-4. PMID: 11992753
Varho T, Komu M, Sonninen P, Holopainen I, Nyman S, Manner T, Sillanpää M, Aula P, Lundbom N
Neurology 1999 May 12;52(8):1668-72. doi: 10.1212/wnl.52.8.1668. PMID: 10331697
Cantz M, Ulrich-Bott B
J Inherit Metab Dis 1990;13(4):523-37. doi: 10.1007/BF01799510. PMID: 2122119

Diagnosis

Aulanko I, Rahikkala E, Moilanen J
Eur Child Adolesc Psychiatry 2023 Oct;32(10):2043-2047. Epub 2022 Jul 7 doi: 10.1007/s00787-022-02031-5. PMID: 35796883Free PMC Article
Huizing M, Hackbarth ME, Adams DR, Wasserstein M, Patterson MC, Walkley SU, Gahl WA; FSASD Consortium
Neurosci Lett 2021 Jun 11;755:135896. Epub 2021 Apr 20 doi: 10.1016/j.neulet.2021.135896. PMID: 33862140Free PMC Article
Barmherzig R, Bullivant G, Cordeiro D, Sinasac DS, Blaser S, Mercimek-Mahmutoglu S
Pediatr Neurol 2017 Sep;74:87-91.e2. Epub 2017 Jun 1 doi: 10.1016/j.pediatrneurol.2017.05.022. PMID: 28662915
Alajoki L, Varho T, Posti K, Aula P, Korhonen T
Dev Med Child Neurol 2004 Dec;46(12):832-7. doi: 10.1017/s0012162204001458. PMID: 15581157
Renlund M
J Pediatr 1984 Feb;104(2):232-6. doi: 10.1016/s0022-3476(84)80998-1. PMID: 6694015

Therapy

Aulanko I, Rahikkala E, Moilanen J
Eur Child Adolesc Psychiatry 2023 Oct;32(10):2043-2047. Epub 2022 Jul 7 doi: 10.1007/s00787-022-02031-5. PMID: 35796883Free PMC Article
Haataja L, Schleutker J, Laine AP, Renlund M, Savontaus ML, Dib C, Weissenbach J, Peltonen L, Aula P
Am J Hum Genet 1994 Jun;54(6):1042-9. PMID: 8198127Free PMC Article

Prognosis

Chapleau A, Mirchi A, Tran LT, Poulin C, Bernard G
Pediatr Neurol 2023 Nov;148:133-137. Epub 2023 Aug 19 doi: 10.1016/j.pediatrneurol.2023.08.013. PMID: 37713976
Knuutinen OA, Oikarainen JH, Suo-Palosaari MH, Kangas SM, Rahikkala EJ, Pokka TM, Moilanen JS, Hinttala RML, Vieira PM, Uusimaa JM
Dev Med Child Neurol 2021 Sep;63(9):1066-1074. Epub 2021 May 5 doi: 10.1111/dmcn.14884. PMID: 33948933
Hult M, Darin N, von Döbeln U, Månsson JE
Acta Paediatr 2014 Dec;103(12):1258-63. Epub 2014 Oct 15 doi: 10.1111/apa.12807. PMID: 25274184
Verheijen FW, Verbeek E, Aula N, Beerens CE, Havelaar AC, Joosse M, Peltonen L, Aula P, Galjaard H, van der Spek PJ, Mancini GM
Nat Genet 1999 Dec;23(4):462-5. doi: 10.1038/70585. PMID: 10581036
Sonninen P, Autti T, Varho T, Hämäläinen M, Raininko R
AJNR Am J Neuroradiol 1999 Mar;20(3):433-43. PMID: 10219409Free PMC Article

Clinical prediction guides

Chapleau A, Mirchi A, Tran LT, Poulin C, Bernard G
Pediatr Neurol 2023 Nov;148:133-137. Epub 2023 Aug 19 doi: 10.1016/j.pediatrneurol.2023.08.013. PMID: 37713976
Coker M, Kalkan-Uçar S, Kitiş O, Uçar H, Gökşen-Simşek D, Darcan S, Gökben S
Turk J Pediatr 2009 Nov-Dec;51(6):605-9. PMID: 20196397
Mancini GM, Verheijen FW, Beerens CE, Renlund M, Aula P
Dev Neurosci 1991;13(4-5):327-30. doi: 10.1159/000112181. PMID: 1817039
Autio-Harmainen H, Oldfors A, Sourander P, Renlund M, Dammert K, Similä S
Acta Neuropathol 1988;75(5):481-90. doi: 10.1007/BF00687135. PMID: 3287834
Wolburg-Buchholz K, Schlote W, Baumkötter J, Cantz M, Holder H, Harzer K
Neuropediatrics 1985 May;16(2):67-75. doi: 10.1055/s-2008-1052546. PMID: 4010893

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