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Disease Report for: Galactosialidosis

Alternative name(s)|Neuraminidase deficiency with beta-galactosidase deficiency
Goldberg syndrome
Deficiency of lysosomal protective protein
Deficiency of cathepsin A
Deficiency of protective protein/cathepsin A
PPCA deficiency
Carboxylpeptidase L deficiency
Mutation|25 mutations (e.g. : C241R_human-CTSA, C331LfsX55_human-CTSA, F173PfsX37_human-CTSA... more)
OMIM: |256540, 613111

(from OMIM)Cathepsin A (CTSA , CATHA protective protein PPCA, beta-galactosidase protective protein PPGB, Carboxypeptidase L) is a ubiquitously expressed multifunctional enzyme, with deamidase, esterase, and carboxypeptidase activities and a preference for substrates with hydrophobic amino acid residues at the P1-prime position. Association with CTSA, as part of the lysosomal multienzyme complex, is essential for stabilization of lysosomal beta-galactosidase (GLB1; 611458), as well as for activation of the lysosomal neuraminidase (NEU1; 608272) (summary by Seyrantepe et al., 2008). Goldberg et al. (1971) described 3 children (2 boys and a girl), in a Mexican family with first-cousin parents, who had a disorder characterized by dwarfism, gargoyle facies, mental retardation, seizures, corneal clouding, macular cherry red spot, beta-galactosidase deficiency, dysostosis multiplex, and hearing loss. The absence of clinically enlarged viscera, vacuolated blood cells, and mucopolysacchariduria was likewise distinctive. The combination of features of a mucopolysaccharidosis and a sphingolipidosis suggested that this should be considered a mucolipidosis. Berard-Badier et al. (1970) described a 17-year-old patient (case 3) who had corneal opacities, a cherry red spot, and the same type of vacuolation of the Kupffer cells as that in the family studied by Goldberg et al. (1971). Most of the cases have been Japanese. Chitayat et al. (1988) described a male with juvenile galactosialidosis who presented at age 19 with hip arthralgia and for evaluation for possible spondyloepiphyseal dysplasia. He had facial 'coarseness,' corneal clouding, mitral and aortic regurgitation, and hepatosplenomegaly. Electron microscopy of skin biopsy and peripheral blood lymphocytes showed membrane-bound fibrillogranular inclusion. The urine showed elevated sialyloligosaccharides but no free sialic acid. Alpha-neuraminidase and beta-galactosidase were both low in fibroblasts. Thomas et al. (1979) found deficiency of neuraminidase in cultured fibroblasts from Goldberg's original patient. Cases of combined deficiency have been reported by Lowden and O'Brien (1979), Hoogeveen et al. (1980), and Wenger et al. (1978). Although this form may be clinically indistinguishable from the sialidoses without deficiency of beta-galactosidase, its distinctness is indicated by complementation in heterokaryon experiments. No evidence of a structural mutation of beta-galactosidase was found (Hoeksema et al., 1980). In normal cells and GM(1)-gangliosidosis cells, beta-galactosidase has a half-life of about 10 days, whereas in the doubly deficient cells it has a half-life of less than 1 day. This reduction is due to enhanced degradation. The form which combines neuraminidase and beta-galactosidase deficiencies appears to have a defect in a 32,000 dalton glycoprotein necessary for activation or proteolytic protection of these 2 enzymes (d'Azzo et al., 1982).

    Title: Turning the backbone into an ankylosed concrete-like structure: Case report
    Kaissi AA, Chehida FB, Grill F, Ganger R, Kircher SG
    Ref: Medicine (Baltimore), 97:e0278, 2018 : PubMed


    Title: Galactosialidosis: historic aspects and overview of investigated and emerging treatment options
    Annunziata I, d'Azzo A
    Ref: Expert Opin Orphan Drugs, 5:131, 2017 : PubMed


    Title: Identification of embryonic lethal genes in humans by autozygosity mapping and exome sequencing in consanguineous families
    Shamseldin HE, Tulbah M, Kurdi W, Nemer M, Alsahan N, Al Mardawi E, Khalifa O, Hashem A, Kurdi A and Alkuraya FS <6 more author(s)>
    Ref: Genome Biol, 16:116, 2015 : PubMed


    Title: Galactosialidosis: review and analysis of CTSA gene mutations
    Caciotti A, Catarzi S, Tonin R, Lugli L, Perez CR, Michelakakis H, Mavridou I, Donati MA, Guerrini R and Morrone A <1 more author(s)>
    Ref: Orphanet J Rare Dis, 8:114, 2013 : PubMed


    Title: A Brazilian galactosialidosis patient given renal transplantation: a case report
    Kiss A, Zen PR, Bittencourt V, Paskulin GA, Giugliani R, d'Azzo A, Schwartz IV
    Ref: J Inherit Metab Dis, 31 Suppl 2:S205, 2008 : PubMed


    Title: New mutations in the PPBG gene lead to loss of PPCA protein which affects the level of the beta-galactosidase/neuraminidase complex and the EBP-receptor
    Malvagia S, Morrone A, Caciotti A, Bardelli T, d'Azzo A, Ancora G, Zammarchi E, Donati MA
    Ref: Mol Genet Metab, 82:48, 2004 : PubMed


    Title: New mutations in two Dutch patients with early infantile galactosialidosis
    Groener J, Maaswinkel-Mooy P, Smit V, van der Hoeven M, Bakker J, Campos Y, d'Azzo A
    Ref: Mol Genet Metab, 78:222, 2003 : PubMed


    Title: Structural and functional study of K453E mutant protective protein/cathepsin A causing the late infantile form of galactosialidosis
    Takiguchi K, Itoh K, Shimmoto M, Ozand PT, Doi H, Sakuraba H
    Ref: J Hum Genet, 45:200, 2000 : PubMed


    Title: Anaemia and thrombocytopenia due to haemophagocytosis in a 7-month-old boy with galactosialidosis
    Olcay L, Gumruk F, Boduroglu K, Coskun T, Tuncbilek E
    Ref: J Inherit Metab Dis, 21:679, 1998 : PubMed


    Title: Molecular pathology of galactosialidosis in a patient affected with two new frameshift mutations in the cathepsin A/protective protein gene
    Richard C, Tranchemontagne J, Elsliger MA, Mitchell GA, Potier M, Pshezhetsky AV
    Ref: Hum Mutat, 11:461, 1998 : PubMed


    Title: Cathepsin A deficiency in galactosialidosis: studies of patients and carriers in 16 families
    Kleijer WJ, Geilen GC, Janse HC, van Diggelen OP, Zhou XY, Galjart NJ, Galjaard H, d'Azzo A
    Ref: Pediatr Res, 39:1067, 1996 : PubMed


    Title: Molecular and biochemical analysis of protective protein/cathepsin A mutations: correlation with clinical severity in galactosialidosis
    Zhou XY, van der Spoel A, Rottier R, Hale G, Willemsen R, Berry GT, Strisciuglio P, Morrone A, Zammarchi E and d'Azzo A <1 more author(s)>
    Ref: Hum Mol Genet, 5:1977, 1996 : PubMed


    Title: Hydrops fetalis in four siblings caused by galactosialidosis
    Landau D, Meisner I, Zeigler M, Bargal R, Shinwell ES
    Ref: Isr J Med Sci, 31:321, 1995 : PubMed


    Title: Protective protein for beta-galactosidase, Ppgb, maps to the distal imprinting region of mouse chromosome 2 but is not imprinted
    Williamson CM, Dutton ER, Beechey CV, Peters J
    Ref: Genomics, 22:240, 1994 : PubMed


    Title: A genetic map of chromosome 20q12-q13.1: multiple highly polymorphic microsatellite and RFLP markers linked to the maturity-onset diabetes of the young (MODY) locus
    Rothschild CB, Akots G, Hayworth R, Pettenati MJ, Rao PN, Wood P, Stolz FM, Hansmann I, Serino K and Bowden DW <2 more author(s)>
    Ref: American Journal of Human Genetics, 52:110, 1993 : PubMed


    Title: Protective protein gene mutations in galactosialidosis
    Shimmoto M, Fukuhara Y, Itoh K, Oshima A, Sakuraba H, Suzuki Y
    Ref: J Clinical Investigation, 91:2393, 1993 : PubMed


    Title: Exclusion map of the gene for neuraminidase from 10(pter-->p15.1)
    Tokano T, Horigome H, Shibata S
    Ref: Clin Genet, 43:166, 1993 : PubMed


    Title: Characteristics of the beta-galactosidase-carboxypeptidase complex in GM1-gangliosidosis and beta-galactosialidosis fibroblasts
    D'Agrosa RM, Hubbes M, Zhang S, Shankaran R, Callahan JW
    Ref: Biochemical Journal, 285 ( Pt 3):833, 1992 : PubMed


    Title: A new point mutation of protective protein gene in two Japanese siblings with juvenile galactosialidosis.
    Fukuhara Y, Takano T, Shimmoto M, Oshima A, Takeda E, Kuroda Y, Sakuraba H, Suzuki Y
    Ref: Brain Dysfunction, 5:319, 1992 : PubMed


    Title: Ring chromosome 20 and possible assignment of the structural gene encoding human carboxypeptidase-L to the distal segment of the long arm of chromosome 20
    Halal F, Chitayat D, Parikh H, Rosenblatt B, Tranchemontagne J, Vekemans M, Potier M
    Ref: American Journal of Medicine Genet, 43:576, 1992 : PubMed


    Title: Human placental beta-galactosidase. Characterization of the dimer and complex forms of the enzyme
    Hubbes M, D'Agrosa RM, Callahan JW
    Ref: Biochemical Journal, 285 ( Pt 3):827, 1992 : PubMed


    Title: Human lysosomal protective protein. Glycosylation, intracellular transport, and association with beta-galactosidase in the endoplasmic reticulum
    Morreau H, Galjart NJ, Willemsen R, Gillemans N, Zhou XY, d'Azzo A
    Ref: Journal of Biological Chemistry, 267:17949, 1992 : PubMed


    Title: Galactosialidosis: clinical and molecular analysis of 19 Japanese patients.
    Takano T, Shimmoto M, Fukuhara Y, Itoh K, Kase R, Takiyama N, Kobayashi T, Oshima A, Sakuraba H, Suzuki Y
    Ref: Brain Dysfunction, 4:271, 1991 : PubMed


    Title: The gene encoding human protective protein (PPGB) is on chromosome 20
    Wiegant J, Galjart NJ, Raap AK, d'Azzo A
    Ref: Genomics, 10:345, 1991 : PubMed


    Title: A mutation in a mild form of galactosialidosis impairs dimerization of the protective protein and renders it unstable
    Zhou XY, Galjart NJ, Willemsen R, Gillemans N, Galjaard H, d'Azzo A
    Ref: EMBO Journal, 10:4041, 1991 : PubMed


    Title: Galactosialidosis: simultaneous deficiency of esterase, carboxy-terminal deamidase and acid carboxypeptidase activities
    Kase R, Itoh K, Takiyama N, Oshima A, Sakuraba H, Suzuki Y
    Ref: Biochemical & Biophysical Research Communications, 172:1175, 1990 : PubMed


    Title: Inheritance of an ovine lysosomal storage disease associated with deficiencies of beta-galactosidase and alpha-neuraminidase
    Prieur DJ, Ahern-Rindell AJ, Murnane RD, Wright RW, Parish SM
    Ref: Journal of Heredity, 81:245, 1990 : PubMed


    Title: Japanese-type adult galactosialidosis: a unique and common splice junction mutation causing exon skipping in the protective protein/carboxypeptidase gene
    Shimmoto M, Takano T, Fukuhara Y, Oshima A, Sakuraba H, Suzuki Y
    Ref: Proc Jpn Acad, 66B:217, 1990 : PubMed


    Title: Combined deficiency of beta-galactosidase and neuraminidase: natural history of the disease in the first 18 years of an American patient with late infantile onset form
    Strisciuglio P, Sly WS, Dodson WE, McAlister WH, Martin TC
    Ref: American Journal of Medicine Genet, 37:573, 1990 : PubMed


    Title: Interspecific genetic complementation analysis of human and sheep fibroblasts with beta-galactosidase deficiency.
    Ahern-Rindell AJ, Murnane RD, Prieur DJ
    Ref: Somat Cell Molec Genet, 15:382, 1989 : PubMed


    Title: Interspecific genetic complementation analysis evidence that the lysosomal storage disease of sheep with deficiencies of beta-galactosidase and alpha-neuraminidase is due to a mutation of the beta-galactosidase structural gene. (Abstract)
    Prieur DJ, Ahern-Rindell AJ
    Ref: American Journal of Human Genetics, 45 (suppl.):A213 only, 1989 : PubMed


    Title: Inherited lysosomal storage disease associated with deficiencies of beta-galactosidase and alpha-neuraminidase in sheep
    Ahern-Rindell AJ, Prieur DJ, Murnane RD, Raghavan SS, Daniel PF, McCluer RH, Walkley SU, Parish SM
    Ref: American Journal of Medicine Genet, 31:39, 1988 : PubMed


    Title: Juvenile galactosialidosis in a white male: a new variant
    Chitayat D, Applegarth DA, Lewis J, Dimmick JE, McCormick AQ, Hall JG
    Ref: American Journal of Medicine Genet, 31:887, 1988 : PubMed


    Title: Expression of cDNA encoding the human protective protein associated with lysosomal beta-galactosidase and neuraminidase: homology to yeast proteases
    Galjart NJ, Gillemans N, Harris A, van der Horst GT, Verheijen FW, Galjaard H, d'Azzo A
    Ref: Cell, 54:755, 1988 : PubMed


    Title: The presence of a reduced amount of 32-kd protective protein is a distinct biochemical finding in late infantile galactosialidosis
    Strisciuglio P, Parenti G, Giudice C, Lijoi S, Hoogeveen AT, d'Azzo A
    Ref: Hum Genet, 80:304, 1988 : PubMed


    Title: Galactosialidosis: a direct evidence that a 46-kilodalton protein restores deficient enzyme activities in fibroblasts
    Nanba E, Tsuji A, Omura K, Suzuki Y
    Ref: Biochemical & Biophysical Research Communications, 144:138, 1987 : PubMed


    Title: An inherited lysosomal storage disease of sheep associated with deficiencies of beta-galactosidase and alpha-neuraminidase. (Abstract)
    Ahern-Rindell AJ, Prieur DJ, Murnane RD
    Ref: American Journal of Human Genetics, 39:A3 only, 1986 : PubMed


    Title: Sialidosis and galactosialidosis: chromosomal assignment of two genes associated with neuraminidase-deficiency disorders
    Mueller OT, Henry WM, Haley LL, Byers MG, Eddy RL, Shows TB
    Ref: Proc Natl Acad Sci U S A, 83:1817, 1986 : PubMed


    Title: Galactosialidosis: molecular heterogeneity among distinct clinical phenotypes
    Palmeri S, Hoogeveen AT, Verheijen FW, Galjaard H
    Ref: American Journal of Human Genetics, 38:137, 1986 : PubMed


    Title: Galactosialidosis: low beta-galactosidase activity in serum after long-term clotting
    Sakuraba H, Iimori Y, Suzuki Y, Kint JA, Akagi M
    Ref: Annals of Neurology, 18:261, 1985 : PubMed


    Title: The chromosomal localization of human beta-galactosidase revisited: a locus for beta-galactosidase on human chromosome 3 and for its protective protein on human chromosome 22
    Sips HJ, de Wit-Verbeek HA, De Wit J, Westerveld A, Galjaard H
    Ref: Hum Genet, 69:340, 1985 : PubMed


    Title: Ultrastructural study on a severe infantile sialidosis (beta-galactosidase-alpha-neuraminidase deficiency)
    Yamano T, Shimada M, Sugino H, Dezawa T, Koike M, Okada S, Yabuuchi H
    Ref: Neuropediatrics, 16:109, 1985 : PubMed


    Title: beta-Galactosidase and neuraminidase deficiency associated with angiokeratoma corporis diffusum
    Ishibashi A, Tsuboi R, Shinmei M
    Ref: Arch Dermatol, 120:1344, 1984 : PubMed


    Title: Combined sialidase (neuraminidase) and beta-galactosidase deficiency. Clinical, morphological and enzymological observations in a patient
    Loonen MC, Reuser AJ, Visser P, Arts WF
    Ref: Clin Genet, 26:139, 1984 : PubMed


    Title: Identification and chromosome location of genes involved in glycoprotein neuraminidase deficiency disorders. (Abstract)
    Mueller OT, Henry WM, Haley LL, Byers MG, Eddy RL, Shows TB
    Ref: American Journal of Human Genetics, 36:205S only, 1984 : PubMed


    Title: Complementation, cross correction, and drug correction studies of combined beta-galactosidase neuraminidase deficiency in human fibroblasts
    Strisciuglio P, Creek KE, Sly WS
    Ref: Pediatr Res, 18:167, 1984 : PubMed


    Title: Presence of activator proteins for the enzymic hydrolysis of GM1 and GM2 gangliosides in normal human urine
    Li YT, Muhiudeen IA, DeGasperi R, Hirabayashi Y, Li SC
    Ref: American Journal of Human Genetics, 35:629, 1983 : PubMed


    Title: Molecular defect in combined beta-galactosidase and neuraminidase deficiency in man
    d'Azzo A, Hoogeveen A, Reuser AJ, Robinson D, Galjaard H
    Ref: Proc Natl Acad Sci U S A, 79:4535, 1982 : PubMed


    Title: Human beta-galactosidase and alpha-neuraminidase deficient mucolipidosis: genetic complementation analysis of the neuraminidase deficiency
    Mueller OT, Shows TB
    Ref: Hum Genet, 60:158, 1982 : PubMed


    Title: Correction of combined beta-galactosidase/neuraminidase deficiency in human fibroblasts
    Hoogeveen A, d'Azzo A, Brossmer R, Galjaard H
    Ref: Biochemical & Biophysical Research Communications, 103:292, 1981 : PubMed


    Title: Combined deficiency of beta-galactosidase and neuraminidase: three affected siblings in a French family
    Maire I, Nivelon-Chevallier AR
    Ref: J Inherit Metab Dis, 4:221, 1981 : PubMed


    Title: Beta-galactosidase-neuraminidase deficiency: restoration of beta-galactosidase activity by protease inhibitors
    Suzuki Y, Sakuraba H, Hayashi K, Suzuki K, Imahori K
    Ref: J Biochem, 90:271, 1981 : PubMed


    Title: beta-Galactosidase-neuraminidase deficiency in adults: deficiency of a freeze-labile neuraminidase in leukocytes and fibroblasts
    Suzuki Y, Sakuraba H, Potier M, Akagi M, Sakai M, Beppu H
    Ref: Hum Genet, 58:387, 1981 : PubMed


    Title: The genetic defect in the various types of human beta-galactosidase deficiency
    Hoeksema HL, De Wit J, Westerveld A
    Ref: Hum Genet, 53:241, 1980 : PubMed


    Title: Genetic heterogeneity in human neuraminidase deficiency
    Hoogeveen AT, Verheijen FW, d'Azzo A, Galjaard H
    Ref: Nature, 285:500, 1980 : PubMed


    Title: Sialidosis: a review of human neuraminidase deficiency
    Lowden JA, O'Brien JS
    Ref: American Journal of Human Genetics, 31:1, 1979 : PubMed


    Title: Neuraminidase deficiency in the original patient with the Goldberg syndrome
    Thomas GH, Goldberg MF, Miller CS, Reynolds LW
    Ref: Clin Genet, 16:323, 1979 : PubMed


    Title: Assignment of structural beta-galactosidase loci to human chromosomes 3 and 22. (Abstract)
    De Wit J, Hoeksema HL, Bootsma D, Westerveld A
    Ref: Cytogenet Cell Genet, 25:217 only, 1979 : PubMed


    Title: Macular cherry-red spots and myoclonus with dementia: coexistent neuraminidase and beta-galactosidase deficiencies
    Wenger DA, Tarby TJ, Wharton C
    Ref: Biochemical & Biophysical Research Communications, 82:589, 1978 : PubMed


    Title: Regional localization of a beta-galactosidase locus on human chromosome 22
    De Wit J, Hoeksema HL, Halley D, Hagemeijer A, Bootsma D, Westerveld A
    Ref: Somatic Cell Genet, 3:351, 1977 : PubMed


    Title: beta-Galactosidase deficiency in juvenile and adult patients. Report of six Japanese cases and review of literature
    Suzuki Y, Nakamura N, Fukuoka K, Shimada Y, Uono M
    Ref: Hum Genet, 36:219, 1977 : PubMed


    Title: Macular cherry-red spots and beta-galactosidase deficiency in an adult. An autopsy case with progressive cerebellar ataxia, myoclonus, thrombocytopathy, and accumulation of polysaccharide in liver
    Suzuki Y, Nakamura N, Shimada Y, Yotsumoto H, Endo H, Nagashima K
    Ref: Archives of Neurology, 34:157, 1977 : PubMed


    Title: Localized beta-galactosidase deficiency. Occurrence in cerebellar ataxia with myoclonus epilepsy and macular cherry-red spot--a new variant of GM1-gangliosidosis?
    Yamamoto A, Adachi S, Kawamura S, Takahashi M, Kitani T
    Ref: Archives of Internal Medicine, 134:627, 1974 : PubMed


    Title: Macular cherry-red spot, corneal clouding, and beta-galactosidase deficiency. Clinical, biochemical, and electron microscopic study of a new autosomal recessive storage disease
    Goldberg MF, Cotlier E, Fichenscher LG, Kenyon K, Enat R, Borowsky SA
    Ref: Archives of Internal Medicine, 128:387, 1971 : PubMed


    Title: [Ultrastructural study of the hepatic parenchyma in mucopolysaccharidosis]
    Berard-Badier M, Adechy-Benkoel L, Chamlian A, Dubois-Gambarelli D, Casanova P, Mariani A
    Ref: Pathol Biol (Paris), 18:117, 1970 : PubMed


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