Sialic Acid Storage Disease and Related Disorders

Strehle, Eugen-Matthias

doi:10.1089/109065703322146795

Cited by 28 publications

(14 citation statements)

References 81 publications

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“…The known forms of SSD are primarily caused by a transport defect across the lysosomal membrane (3,7 ), which leads to the accumulation of free sialic acid [Nacetylneuraminic acid (NANA); Fig. 1] in tissues, fibroblasts, and urine.…”

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confidence: 99%

Quantification of Free Sialic Acid in Urine by HPLC–Electrospray Tandem Mass Spectrometry: A Tool for the Diagnosis of Sialic Acid Storage Disease

et al. 2004

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Background: Sialic acid storage diseases (SSDs) are severe autosomal recessive neurodegenerative disorders caused by a transport defect across the lysosomal membrane, which leads to accumulation of sialic acid in tissues, fibroblasts, and urine. Defective free sialic acid transport can be established by quantification of free sialic acid in urine. Methods: Urine sample size was adjusted to the equivalent of 100 nmol of creatinine. After addition of 2-keto-3-deoxy-D-glycero-D-galactonononic acid as internal standard, samples were diluted with water to an end volume of 250 L. We used 10 L for HPLC-tandem mass spectrometric analysis in the negative electrospray ionization mode, monitoring transitions m/z 308.33m/z 86.9 (sialic acid) and m/z 267.23m/z 86.9 (internal standard). The overall method was validated and studied for ion suppression, interfering compounds, and pH effects. Samples from controls (n ‫؍‬ 72) and SSD patients (n ‫؍‬ 3) were analyzed. Results: The limit of detection was 3 mol/L. Intraassay imprecision (CV; n ‫؍‬ 10) was 6%, 3%, and 2% at 30, 130, and 1000 mmol/mol creatinine, respectively; corresponding interassay CV (n ‫؍‬ 10) were 5%, 5%, and 2%. Recovery was 109% (100 -1000 mmol/mol creatinine). (2, 4 -6 ).The known forms of SSD are primarily caused by a transport defect across the lysosomal membrane (3, 7 ), which leads to the accumulation of free sialic acid [Nacetylneuraminic acid (NANA); Fig. 1] in tissues, fibroblasts, and urine. The origin of the transport defect lies in a mutation in the SLC17A5 gene, which encodes for sialin protein (8, 9 ).Defective free sialic acid transport can be established by quantitative analysis of NANA in urine relative to the concentration of creatinine. Several types of analysis are available to quantify NANA, including colorimetric methods (10, 11 ), thin-layer chromatography (12 ), gas chromatography-mass spectrometry (12, 13 ), HPLC with fluorescence detection (14 ), HPLC with ultraviolet detection (15 ), enzymatic assays (14, 16 ), high-performance anionexchange chromatography with pulsed amperometric detection (HPAE-PAD) (17,18 ), and HPLC with mass spectrometry (HPLC-MS) (19,20 ). The main disadvantages of these methods are a lack of selectivity, a lack of speed, or both. For example, enzymatic methods appear to be more accurate than colorimetric methods (16,21 ), but neither method can differentiate among different neuraminic acids; HPAE-PAD, used mainly for the analysis of sialic acids released from glycoconjugates, can reduce the possibility of interferences by relatively long gradient separations. 20 ) are more selective and sensitive, but they are still time-consuming, multistep methods that have not been validated as a rapid diagnostic tool.In this report we describe and validate a simple, rapid, selective, and sensitive method for the analysis of NANA in urine samples based on HPLC combined with tandem MS (HPLC-tMS). The deaminated sialic acid 2-keto-3-deoxy-d-glycero-d-galactonononic acid (KDN) was used as an internal standard (IS) (17, 22 ) (s...

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Quantification of Free Sialic Acid in Urine by HPLC–Electrospray Tandem Mass Spectrometry: A Tool for the Diagnosis of Sialic Acid Storage Disease

et al. 2004

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“…Thus, both neuraminidase and β-galactosidase enzymes are inactive. Although it is very similar to sialidosis clinically, they are completely different genetic diseases (11,12).…”

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confidence: 97%

“…There is deficiency of sialin which is a lysosomal membrane protein in Salla disease and infantile sialic acid storage disease. The genetic characteristics are completely different from sialidosis and should be differentiated (11,13).…”

Section: Discussionmentioning

confidence: 99%

Nadir bir immün olmayan hidrops fetalis nedeni: doğumsal siyalidoz

...

2012

Tpa

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Ca se Re port Sum marySialidosis is a rare congenital lysosomal storage disease with autosomal recessive transmission caused by a deficiency of alpha-N-acetylneuraminidase (sialidase). The findings begin in the intrauterine period in congenital type of sialidosis and the cases die in the postnatal period due to hydrops fetalis with multiorgan failure. Here, a case of premature baby born to a consanguineous parents and diagnosed as sialidosis with hydrops fetalis is presented. It was learned that the first pregnancy of the mother ended in spontaneous abortion and the second pregnancy was ended up with intrauterine exitus due to hydrops fetalis in the 28 th gestational age. On the first physical examination, generalized edema, abdominal distantion due to hepatomegaly and generalized ascites was observed. Direct hyperbilirubinemia and cytoplasmic vacuoli in the lymphomonocyte series in both the bone marrow and peripheral blood smear were detected. The same vacuoli were also observed in hepatocytes in the hystopathological sections of the liver biopsy. Sialidosis was diagnosed by showing that there was no activity of sialidase enzyme in the fibroblast culture. The case died due to cardiorespiratory insufficiency on the 53 rd day of admission. In cases with hydrops fetalis which can have various etiologies, careful examination of the peripheral smear is very important in the differential diagnosis in addition to detailed familial history and physical examination. (Turk Arch Ped 2012; 47: 286-289)

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“…However, in the present cases the facial coarseness is distinct, the cataract is present in only one of the patients, is unilateral and probably post-traumatic, and the serum CK levels are normal, making this diagnosis unlikely. Sialic acid disorders [Strehle, 2003] such as Salla disease (OMIM 604369), and atypical Refsum disorder (OMIM 614879) [Waterham and Ebberink, 2012], show clinical resemblance but metabolic studies excluded both entities. Hypoplasia of the pons and cerebellum with progressive volume loss can be characteristic of congenital disorder of glycosylation type 1a [Grünewald, 2009], but many other manifestations differ and isoelectric focussing of transferrin yielded normal results.…”

Section: Discussionmentioning

confidence: 99%

Intellectual disability, coarse face, relative macrocephaly, and cerebellar hypotrophy in two sisters

Sousa¹,

Ramos

Garcia

et al. 2013

American J of Med Genetics Pt A

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We report on two Portuguese sisters with a very similar phenotype characterized by severe intellectual disability, absent speech, relative macrocephaly, coarse face, cerebellar hypotrophy, and severe ataxia. Additional common features include increased thickness of the cranial vault, delayed dental eruption, talipes equino-varus, clinodactyly, and camptodactyly of the fifth finger. The older sister has retinal dystrophy and the younger sister has short stature. Their parents are consanguineous. We suggest this condition constitutes a previously unreported autosomal recessive entity.

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Sialic Acid Storage Disease and Related Disorders

Cited by 28 publications

References 81 publications

Quantification of Free Sialic Acid in Urine by HPLC–Electrospray Tandem Mass Spectrometry: A Tool for the Diagnosis of Sialic Acid Storage Disease

Quantification of Free Sialic Acid in Urine by HPLC–Electrospray Tandem Mass Spectrometry: A Tool for the Diagnosis of Sialic Acid Storage Disease

Nadir bir immün olmayan hidrops fetalis nedeni: doğumsal siyalidoz

Intellectual disability, coarse face, relative macrocephaly, and cerebellar hypotrophy in two sisters

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