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Sialic acid storage disease, severe infantile type(ISSD)

MedGen UID:
203367
Concept ID:
C1096902
Disease or Syndrome
Synonyms: Infantile Free Sialic Acid Storage Disease; Infantile Sialic Acid Storage Disease; Infantile sialic acid storage disorder; ISSD; N-Acetylneuraminic acid storage disease; NANA STORAGE DISEASE; Sialuria, infantile form
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
SNOMED CT: Infantile sialic acid storage disease (34566007); Sialic acid storage disease, severe infantile type (34566007); Sialuria, infantile type (34566007)
 
Gene: SLC17A5
Cytogenetic location: 6q13
OMIM®: 269920

Disease characteristics

Excerpted from the GeneReview: Free Sialic Acid Storage Disorders
The allelic disorders of free sialic acid metabolism — Salla disease, intermediate severe Salla disease, and infantile free sialic acid storage disease (ISSD) — are neurodegenerative disorders resulting from increased lysosomal storage of free sialic acid. The mildest phenotype is Salla disease, which is characterized by normal appearance and neurologic findings at birth followed by slowly progressive neurologic deterioration resulting in mild to moderate psychomotor retardation, spasticity, athetosis, and epileptic seizures. The most severe phenotype is ISSD, characterized by severe developmental delay, coarse facial features, hepatosplenomegaly, and cardiomegaly; death usually occurs in early childhood. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  GeneReview Scope  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
David Adams  |  William A Gahl   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/269920
From GHR
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. 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. 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. People with intermediate severe Salla disease have signs and symptoms that fall between those of ISSD and Salla disease in severity.  http://ghr.nlm.nih.gov/condition/sialic-acid-storage-disease

Clinical features

Nephrotic syndrome
MedGen UID:
504341
Concept ID:
CN000100
Finding
Nephrotic syndrome is a collection of findings resulting from glomerular dysfunction with an increase in glomerular capillary wall permeability associated with pronounced proteinuria. Nephrotic syndrome refers to the constellation of clinical findings that result from severe renal loss of protein, with Proteinuria and hypoalbuminemia, edema, and hyperlipidemia.
Gingival overgrowth
MedGen UID:
504394
Concept ID:
CN000205
Finding
Hyperplasia of the gingiva (FMA:59762, that is, a thickening of the soft tissue overlying the alveolar ridge. The degree of thickening ranges from involvement of the interdental papillae alone to gingival overgrowth covering the entire tooth crown.
High palate
MedGen UID:
504397
Concept ID:
CN000211
Finding
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Ptosis
MedGen UID:
504471
Concept ID:
CN000475
Finding
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Global developmental delay
MedGen UID:
504774
Concept ID:
CN001157
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.
Cerebral atrophy
MedGen UID:
505074
Concept ID:
CN001862
Finding
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Abnormality of the thorax
MedGen UID:
427834
Concept ID:
CN000719
Finding
Any abnormality of the thorax (the region of the body formed by the sternum, the thoracic vertebrae and the ribs).
Hydrops fetalis
MedGen UID:
504951
Concept ID:
CN001623
Finding
The abnormal accumulation of fluid in two or more fetal compartments, including ascites, pleural effusion, pericardial effusion, and skin edema.
Ascites
MedGen UID:
416
Concept ID:
C0003962
Finding
A disorder characterized by accumulation of serous or hemorrhagic fluid in the peritoneal cavity.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Hepatomegaly
MedGen UID:
505165
Concept ID:
CN002031
Finding
Abnormally increased size of the liver.
Hypopigmentation of the skin
MedGen UID:
446388
Concept ID:
CN000946
Finding
A reduction of skin color related to a decrease in melanin production and deposition.
Fair hair
MedGen UID:
500923
Concept ID:
CN002075
Finding
A lesser degree of hair pigmentation than would otherwise be expected.
Cardiomegaly
MedGen UID:
5459
Concept ID:
C0018800
Finding
hypertrophy or enlargement of the heart.
Congestive heart failure
MedGen UID:
504881
Concept ID:
CN001488
Finding
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Hydrops fetalis
MedGen UID:
504951
Concept ID:
CN001623
Finding
The abnormal accumulation of fluid in two or more fetal compartments, including ascites, pleural effusion, pericardial effusion, and skin edema.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Muscular hypotonia
MedGen UID:
504768
Concept ID:
CN001147
Finding
Muscular hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. Hypotonia is characterized by a diminished resistance to passive stretching.
Abnormality of the foot
MedGen UID:
427893
Concept ID:
CN001600
Finding
An abnormality of the skeleton of foot.

Recent clinical studies

Etiology

Kirchner L, Kircher S, Salzer-Muhar U, Paschke E, Birnbacher R, Stöckler-Ipsiroglu S
Pediatr Neurol 2003 Apr;28(4):313-7. PMID: 12849889
Varho TT, Alajoki LE, Posti KM, Korhonen TT, Renlund MG, Nyman SR, Sillanpää ML, Aula PP
Pediatr Neurol 2002 Apr;26(4):267-73. PMID: 11992753
Salomäki P, Aula N, Juvonen V, Renlund M, Aula P
Prenat Diagn 2001 May;21(5):354-8. doi: 10.1002/pd.68. PMID: 11360275
Sewell AC, Poets CF, Degen I, Stöss H, Pontz BF
Am J Med Genet 1996 May 3;63(1):203-8. doi: 10.1002/(SICI)1096-8628(19960503)63:1<203::AID-AJMG36>3.0.CO;2-Q. PMID: 8723111
Vamos E, Libert J, Elkhazen N, Jauniaux E, Hustin J, Wilkin P, Baumkötter J, Mendla K, Cantz M, Strecker G
Prenat Diagn 1986 Nov-Dec;6(6):437-46. PMID: 3809113

Diagnosis

van den Bosch J, Oemardien LF, Srebniak MI, Piraud M, Huijmans JG, Verheijen FW, Ruijter GJ
J Inherit Metab Dis 2011 Oct;34(5):1069-73. Epub 2011 May 27 doi: 10.1007/s10545-011-9351-3. [Epub ahead of print] PMID: 21617927Free PMC Article
Debray FG, Lefebvre C, Colinet S, Segers K, Stevens R
J Pediatr 2011 Jan;158(1):165, 165.e1. Epub 2010 Aug 21 doi: 10.1016/j.jpeds.2010.06.057. [Epub ahead of print] PMID: 20728092
Mochel F, Yang B, Barritault J, Thompson JN, Engelke UF, McNeill NH, Benko WS, Kaneski CR, Adams DR, Tsokos M, Abu-Asab M, Huizing M, Seguin F, Wevers RA, Ding J, Verheijen FW, Schiffmann R
Ann Neurol 2009 Jun;65(6):753-7. doi: 10.1002/ana.21624. PMID: 19557856Free PMC Article
Landau D, Cohen D, Shalev H, Pinsk V, Yerushalmi B, Zeigler M, Birk OS
Mol Genet Metab 2004 Jun;82(2):167-72. doi: 10.1016/j.ymgme.2004.03.005. PMID: 15172005
Stevenson RE, Lubinsky M, Taylor HA, Wenger DA, Schroer RJ, Olmstead PM
Pediatrics 1983 Oct;72(4):441-9. PMID: 6889058

Therapy

Mochel F, Sedel F, Vanderver A, Engelke UF, Barritault J, Yang BZ, Kulkarni B, Adams DR, Clot F, Ding JH, Kaneski CR, Verheijen FW, Smits BW, Seguin F, Brice A, Vanier MT, Huizing M, Schiffmann R, Durr A, Wevers RA
Brain 2009 Mar;132(Pt 3):801-9. Epub 2009 Jan 19 doi: 10.1093/brain/awn355. [Epub ahead of print] PMID: 19153153Free PMC Article
Boomkamp SD, Butters TD
Subcell Biochem 2008;49:441-67. doi: 10.1007/978-1-4020-8831-5_17. PMID: 18751922
Ioannou YA, Zeidner KM, Gordon RE, Desnick RJ
Am J Hum Genet 2001 Jan;68(1):14-25. Epub 2000 Dec 13 doi: 10.1086/316953. [Epub ahead of print] PMID: 11115376Free PMC Article
Iribarren C, Sempos CT, Eckfeldt JH, Folsom AR
Atherosclerosis 1998 Jul;139(1):189-95. PMID: 9699907
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

Landau D, Cohen D, Shalev H, Pinsk V, Yerushalmi B, Zeigler M, Birk OS
Mol Genet Metab 2004 Jun;82(2):167-72. doi: 10.1016/j.ymgme.2004.03.005. PMID: 15172005
Kirchner L, Kircher S, Salzer-Muhar U, Paschke E, Birnbacher R, Stöckler-Ipsiroglu S
Pediatr Neurol 2003 Apr;28(4):313-7. PMID: 12849889
Kleta R, Aughton DJ, Rivkin MJ, Huizing M, Strovel E, Anikster Y, Orvisky E, Natowicz M, Krasnewich D, Gahl WA
Am J Med Genet A 2003 Jul 1;120A(1):28-33. doi: 10.1002/ajmg.a.20024. PMID: 12794688
Sewell AC, Poets CF, Degen I, Stöss H, Pontz BF
Am J Med Genet 1996 May 3;63(1):203-8. doi: 10.1002/(SICI)1096-8628(19960503)63:1<203::AID-AJMG36>3.0.CO;2-Q. PMID: 8723111
Stevenson RE, Lubinsky M, Taylor HA, Wenger DA, Schroer RJ, Olmstead PM
Pediatrics 1983 Oct;72(4):441-9. PMID: 6889058

Clinical prediction guides

Mochel F, Engelke UF, Barritault J, Yang B, McNeill NH, Thompson JN, Vanderver A, Wolf NI, Willemsen MA, Verheijen FW, Seguin F, Wevers RA, Schiffmann R
Neurology 2010 Jan 26;74(4):302-5. doi: 10.1212/WNL.0b013e3181cbcdc4. PMID: 20101035Free PMC Article
Kleta R, Aughton DJ, Rivkin MJ, Huizing M, Strovel E, Anikster Y, Orvisky E, Natowicz M, Krasnewich D, Gahl WA
Am J Med Genet A 2003 Jul 1;120A(1):28-33. doi: 10.1002/ajmg.a.20024. PMID: 12794688
Sewell AC, Poets CF, Degen I, Stöss H, Pontz BF
Am J Med Genet 1996 May 3;63(1):203-8. doi: 10.1002/(SICI)1096-8628(19960503)63:1<203::AID-AJMG36>3.0.CO;2-Q. PMID: 8723111
Berra B, Gornati R, Rapelli S, Gatti R, Mancini GM, Ciana G, Bembi B
Am J Med Genet 1995 Jul 31;58(1):24-31. doi: 10.1002/ajmg.1320580107. PMID: 7573152
Paschke E, Trinkl G, Erwa W, Pavelka M, Mutz I, Roscher A
Clin Genet 1986 May;29(5):417-24. PMID: 3742847

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