GM2 gangliosidosis II(Sandhoff disease) is a lysosomal storage disease due to deficiency of beta-hexosaminidase activity, transmitted by mode of autosomal recessive. Clinical features are so variable, ranging from infantile onset resulting death before 4 years, to subacute or chronic forms with more slowly progressive neurologic condition. We experienced a case of GM2 gangliosidosis II in a 14 months old male who had developmental deterioration and seizures, so we report and review the related literatures.
beta-N-Acetylhexosaminidases ; Gangliosidoses, GM2* ; Hexosaminidases ; Humans ; Infant ; Lysosomal Storage Diseases ; Male ; Seizures

Tay-Sachs disease is an autosomal recessive, neurodegenerative disorder that results from excessive storage of the cell membrane glycolipid, and GM2 ganglioside within the lysosomes of cells. This disease is caused by deficiency of the isoenzyme beta-hexosaminidase A, produced in the endoplasmic reticulum. Patients with Tay-Sachs disease are characterized by normal motor development in the first few months of life, followed by progressive weakness and loss of motor skills beginning around 2 to 6 months of life. Neurodegeneration is relentless, with death occurring by the age of 4 or 5 years. Tay-Sachs disease could be diagnosed by hexosaminidase enzyme assay and DNA analysis of HEXA gene. However, specific treatment has not been developed. We report here on a case of Tay- Sachs disease in 18-month-old male who presented with delayed development and seizure. This patient showed hyperacusis and cherry red spot in macula on examination of the fundus. The hexosaminidase A activity was zero percent in the enzymatic assay and DNA analysis identified a mutation that glutamine is substituted by stop codon at position 390(Q390X). This patient is the first case of Tay-Sachs disease in Korea diagnosed by enzymatic assay and DNA analysis.
beta-N-Acetylhexosaminidases ; Cell Membrane ; Codon, Terminator ; DNA* ; Endoplasmic Reticulum ; Enzyme Assays* ; G(M2) Ganglioside ; Glutamine ; Hexosaminidase A ; Hexosaminidases ; Humans ; Hyperacusis ; Infant ; Korea* ; Lysosomes ; Male ; Motor Skills ; Neurodegenerative Diseases ; Prunus ; Seizures ; Tay-Sachs Disease*

PURPOSE: Urinary N-acetyl-beta-D-glucosaminidase (NAG) has been known to reflect the damage of proximal tubular cells in the early stages of renal disease. Recent studies have demonstrated that tubular grade predicted renal outcome better than did other histological parameters in IgA nephropathy. We evaluated the meaning of urinary NAG in relation with initial histological features and renal outcomes in early subclinical IgA nephropathy. METHODS: Among the firstly diagnosed IgA nephropathy patients from Jan 2001 to Dec 2002, 43 subjects were selected with the criteria of normal renal function and 24-h urinary protein excretion <3.5 g/day. The subjects were followed for 2 years. Pathologic lesion was graded according to HASS classification and semiquantitative scorings, from 0 to 3, were carried out for glomerular (GG), interstitial (IG), tubular (TG), and vascular (VG) lesion. RESULTS: The subjects consisted of 20 male and 23 female with mean age of 30+/-13 years, baseline blood pressure 116+/-15/74+/-10 mmHg, Cr 1.03+/-0.24 mg/dL, Ccr 88+/-19 mL/min, 24-h urinary protein excretion (UPER) 1, 790+/-1, 610 mg/24-h, urinary NAG 11.8+/-11.0 U/g cr at the time of biopsy. Hass subclass was correlated significantly with glomerular, tubular, and interstitial grades (all p<0.05). In comparison with clinical parameters, glomerular grade was significantly related with 24-h UPER (p<0.05) and tubular grade was significantly related with systolic blood pressure (p<0.05). Urinary NAG level at the time of biopsy show significant correlation with tubular grade (p<0.05). Progression of renal disease occurred in nine patients (20.9%). The patients with renal disease progression showed significantly low baseline Ccr, high 24-h UPER, and high NAG (all p<0.05). In pathological findings, tubular grade was significantly related with renal prognosis (p<0.05). In regression analysis, tubular grade was a independent predictor of renal prognosis among above four parameters showing significant differences. In survival analysis, tubular grade 0, 1 and grade 2, 3 showed significant difference in renal survival as compared to each other. The patients with baseline NAG urinary NAG above 10 U/g Cr showed significantly worse renal survival as compared with those below 10 U/g Cr (p<0.05). CONCLUSION: Tubular lesion is an independent factor associated with renal progression in these patients. Urinary NAG reflects well the degree of tubular lesion at the time of biopsy. We carefully suggest, therefore, that the measurement of urinary NAG level is helpful to estimate tubular lesion and predict renal prognosis in subclinical asymptomatic IgA nephropathy patients before they undergo renal biopsy.
Acetylglucosaminidase ; Biopsy ; Blood Pressure ; Classification ; Disease Progression ; Female ; Glomerulonephritis, IGA* ; Hexosaminidases* ; Humans ; Immunoglobulin A* ; Male ; Prognosis*

Siglecs are sialic acid binding Ig-like lectins, subset of the immunoglobulin superfamily. They are characterized by a homologous N-terminal V-set Ig-like domain and C2 set Ig-like domains. N-terminal domains have sialic acid binding activity. In humans, 11 Siglecs have been described sialoadhesin(Siglec-1), CD22(Siglec-2), CD33(Siglec-3), MAG(Siglec-4), more recently described CD33-related Siglecs(Siglec 5-11). Siglecs express most signal via immunoreceptor tyrosine-based inhibition motif(ITIM) cytoplasmic domains. The cytoplasmic tails of all Siglecs except sialoadhesin have one or more tyrosine residues within potential signaling motifs. Inhibitory function of other Siglecs such as Siglec-7 or Siglec-9 was shown in RBL-2H3 cells. Co-crosslinking of Siglec-7 or Siglec-9 and Fc epsilon R1 substantially reduced the serotonin release of RBL-7 and RBL-9 cells. Siglec-8 is expressed on human eosinophils, mast cells and basophils. Siglec-8 has two tyrosine motifs, a proximal motif and a distal motif. They have some inhibitory functions in immune system. We have observed that Siglec-8 is able to inhibit the IgE receptor-mediated beta-hexosaminidase release of RBL-2H3 cells following co-crosslinking. Co-crosslinking of Siglec-8 and Fc epsilon R1 reduced the hexosaminidase release of RBL-2H3 cells. These results show that Siglec-8 is as potent as Siglec-7 and Siglec-9 in delivering inhibitory signals to RBL-2H3 cells. Siglec-8 should be a new member of the inhibitory receptor superfamily and the membrane-proximal ITIM is essential for the inhibitory function of Siglec-8 molecules. Although these molecules present specific marker for the allergic cell types, more work is needed to understand the signaling mechanism and the role in various disease processes.
Basophils ; beta-N-Acetylhexosaminidases ; Cytoplasm ; Eosinophils ; Hexosaminidases ; Humans ; Immune System ; Immunoglobulin E ; Immunoglobulins ; Inflammation* ; Lectins ; Mast Cells ; N-Acetylneuraminic Acid ; Serotonin ; Sialic Acid Binding Ig-like Lectin 1 ; Sialic Acid Binding Immunoglobulin-like Lectins* ; Tyrosine

Tay-Sachs Disease (TSD), the most common form of GM(2) gangliosidosis, is an autosomal recessive inborn lysosomal glycosphingolipid storage disease which is resulted from the mutations that affect the alpha-subunit locus on chromosome 15 and cause a severe deficiency of hexosaminidase A. It is characterized by normal motor development in the first few months of life, followed by progressive weakness and loss of motor skills beginning around 6 months of life. Neurodegeneration is relentless and manifested as relentless motor and mental deterioration, beginning with motor incoordination, mental obtundation leading to muscular flaccidity, blindness, and increasing dementia, with death occurring by the age of 4 or 5 years. We report a successful anesthetic management in a patient with Tay-Sachs Diseases for tracheostomy and feeding gastrostomy.
Ataxia ; Blindness ; Chromosomes, Human, Pair 15 ; Dementia ; Gangliosidoses ; Gastrostomy ; Hexosaminidase A ; Hexosaminidases ; Humans ; Motor Skills ; Muscle Hypotonia ; Tay-Sachs Disease* ; Tracheostomy

<b>OBJECTIVEb>To explore the clinical features and molecular mutation of HEXB gene in a case with juvenile Sandhoff disease.

<b>METHODb>We retrospectively reviewed the clinical, neuroimaging and biochemical findings in this Chinese child with juvenile Sandhoff disease. Hexosaminidase A and hexosaminidase A & B activities were measured in blood leukocytes by fluorometric assay. HEXB gene molecular analysis was performed by PCR and direct sequencing.

<b>RESULTb>The 9-year-old boy was admitted for psychomotor regression. He presented slowly progressive gait disorder and dysarthria during the last three years. Cranial MRI revealed a marked cerebellar atrophy with normal intensity in the thalamus and basal ganglia. Brain MRS showed normal in the thalamus and basal ganglia. Hexosaminidase A was 69.5 (mg·h) [normal controls 150-360 nmol/(mg·h)], hexosaminidase A & B activity was 119 nmol/(mg·h)[normal controls 600-3 500 nmol/(mg·h)], confirming the diagnosis of Sandhoff disease. The patient was a compound heterozygote for a novel deletion mutation c.1404delT (p. P468P fsX62) and a reported mutation c.1509-26G>A.

<b>CONCLUSIONb>The clinical features of juvenile Sandhoff disease include ataxia, dysarthria and cerebellar atrophy. The enzyme assay and molecular analysis of HEXB gene can confirm the diagnosis of Sandhoff disease. The novel mutation c.1404delT(p. P468P fsX62) is a disease-related mutation.

Brain ; diagnostic imaging ; pathology ; Cerebellar Ataxia ; diagnosis ; enzymology ; genetics ; Child ; DNA Mutational Analysis ; Heterozygote ; Hexosaminidase A ; blood ; metabolism ; Hexosaminidase B ; blood ; metabolism ; Humans ; Leukocytes ; enzymology ; Magnetic Resonance Imaging ; Male ; Mutation ; Radiography ; Retrospective Studies ; Sandhoff Disease ; diagnosis ; enzymology ; genetics ; beta-Hexosaminidase beta Chain ; genetics

Endo-β-N-acetylglucosaminidase is used widely in the glycobiology studies and industries. In this study, a new endo-β-N-acetylglucosaminidase, designated as Endo SA, was cloned from Streptomyces alfalfae ACCC 40021 and expressed in Escherichia coli BL21 (DE3). The purified recombinant Endo SA exhibited the maximum activity at 35 ºC and pH 6.0, good thermo/pH stability and high specific activity (1.0×10⁶ U/mg). It displayed deglycosylation activity towards different protein substrates. These good properties make EndoSA a potential tool enzyme and industrial biocatalyst.
Cloning, Molecular ; Enzyme Stability ; Escherichia coli ; genetics ; Gene Expression ; Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase ; genetics ; metabolism ; Recombinant Proteins ; genetics ; metabolism ; Streptomyces ; enzymology ; genetics

ESWL is a safe and effective treatment for renal calculi. However, on destruction of the stone, the pressure of shock waves produces renal microdamage. Urinary enzyme testing has been used to diagnosis and monitor various types of renal injured. Three urinary enzymes, N-acetyl-beta- glucosaminidase, beta-galactosidase, gamma-glutamyl transferase in 24 hour urine were monitored in 20 patients before and after ESWL and in 5 controls. The ESWL, a single session treatment, was performed using EDAP LT-01. The amount of the shock wave treated was same regardless of stone size and location. The results were obtained as follows. 1. Post-ESWL N-acetyl-beta-glucosaminidase level was higher than that of control on day 1 and showed a rapid decrease on day 3, and returned to normal by day 28. 2. Post-ESWL beta-galactosidase level was higher than that of control on day 1 and was still higher on day 7, and returned to normal by day 28. 3. Post-ESWL gamma-glutamyl transferase level reached to a peak on day 1 and showed a rapid decrease on day 3, and returned to normal by day 28. In summary, ESWL for renal stones elevates urinary enzymes transiently, which was on peak one day after the treatment and returned to nearly normal level by 1 month after the treatment. Therefore, urinary enzymes seem to be useful in evaluation of the functional recovery of the kidney after ESWL.
beta-Galactosidase ; Diagnosis ; Hexosaminidases ; Humans ; Kidney ; Kidney Calculi ; Shock ; Transferases

<b>OBJECTIVEb>To study the molecular mechanism of GM(2) gangliosidosis.

<b>METHODSb>The skin fibroblasts from 4 patients with GM(2) gangliosidosis were subjected to culture. Enzyme activities assay, Western blot and immunocytochemical analysis were performed using the cultured fibroblasts.

<b>RESULTSb>The hexosaminidase (Hex) activities of 4 patients with GM(2) gangliosidosis were significantly decreased. The activities were 12% 3% 15% and 6% of control values, respectively. Western blot analysis indicated that the amount of Hex mature alpha- and beta- subunits (alpha m, beta m) was decreased in cells from patients 2 and 3, but only decreased alpha m was found in patient 1 and both alpha m and beta m were normal in cells from patient 4. Immunocytochemical analysis revealed the accumulated GM(2) ganglioside in cells from patients 1-4.

<b>CONCLUSIONb>The pathogenesis of GM(2) gangliosidosis was associated with deficiency of Hex alpha m and beta m and GM(2) activator caused by HEXA, HEXB and GM(2)A gene mutations.

Adult ; Blotting, Western ; Cells, Cultured ; Child, Preschool ; Female ; Gangliosidoses, GM2 ; enzymology ; pathology ; Hexosaminidase A ; Hexosaminidase B ; Humans ; Infant ; Male ; Protein Subunits ; metabolism ; beta-N-Acetylhexosaminidases ; metabolism

OBJECTIVE: To detect potential mutations of HEXB gene in an infant with Sandhoff disease (SD). METHODS: Genomic DNA was extracted from peripheral blood sample of the infant. All coding exons (exons 1 to 14) and splicing sites of the HEXB gene were subjected to PCR amplification and direct sequencing.PubMed Protein BLAST system was employed to analyze cross-species conservation of the mutant amino acid. PubMed BLAST CD-search was performed to identify functional domains destroyed by thecandidate mutations. Impact of the mutations was analyzed with software including PolyPhen-2, Mutation Taster and SIFT. Whole-exome sequencing was carried out to identify additional mutations. RESULTS: The infant was found to carry compound heterozygous mutations c.1652G>A(p.Cys551Tyr) and c.1389C>G (p.Tyr463*) of the HEXB gene. The c.1389C>G (p.Tyr463*) mutation may lead to destruction of two functional domains in β subunit of the Hex protein. The c.1652G>A(p.Cys551Tyr) mutation, unreported previously,was predicted to be probably damaging by Bioinformatic analysis. CONCLUSION Compound heterozygous mutations c.1652G>A(p.Cys551Tyr) and c.1389C>G (p.Tyr463*) in the HEXB gene probably underlie the disease in this patient.
DNA Mutational Analysis ; Exons ; Heterozygote ; Humans ; Infant ; Mutation ; Polymerase Chain Reaction ; Sandhoff Disease ; genetics ; beta-Hexosaminidase beta Chain ; genetics