Alternative titles; symbols
SNOMEDCT: 35691006; ORPHA: 351; DO: 0080540;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 20q13.12 | Galactosialidosis | 256540 | Autosomal recessive | 3 | CTSA | 613111 |
A number sign (#) is used with this entry because of evidence that galactosialidosis (GSL) is caused by homozygous or compound heterozygous mutation in the CTSA gene (613111) on chromosome 20q13.
Galactosialidosis (GSL) is a lysosomal storage disease associated with a combined deficiency of beta-galactosidase (611458) and neuraminidase (608272), secondary to a defect in protective protein/cathepsin A (PPCA). All patients have clinical manifestations typical of a lysosomal disorder, such as coarse facies, cherry red spots, vertebral changes, foam cells in the bone marrow, and vacuolated lymphocytes. Three phenotypic subtypes are recognized. The early infantile form is associated with fetal hydrops, edema, ascites, visceromegaly, skeletal dysplasia, and early death. The late infantile type is characterized by hepatosplenomegaly, growth retardation, cardiac involvement, and rare occurrence of neurologic signs. The juvenile/adult form is characterized by myoclonus, ataxia, angiokeratoma, mental retardation, neurologic deterioration, absence of visceromegaly, and long survival. The majority of reported patients belong to the juvenile/adult group and are mainly of Japanese origin (summary by d'Azzo et al., 2001).
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. Berard-Badier et al. (1970) had 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).
Widespread hemangiomas, possibly like the angiokeratomas of Fabry disease (301500), were described by Loonen et al. (1984) in a Japanese man in his 30s. These, together with telangiectases of the conjunctiva, had been present from age 8 years. Ishibashi et al. (1984) concluded that angiokeratoma has been observed only in Japanese cases with combined beta-galactosidase and neuraminidase deficiency.
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. The patient did not have macular cherry red spots, neurologic abnormalities, or mental retardation.
In a female patient described by Andria et al. (1981) and studied biochemically by Strisciuglio et al. (1984), Strisciuglio et al. (1990) described the natural history of late infantile onset galactosialidosis during the first 18 years of life. Clinical findings in the first months of life included somewhat coarse facial features and hepatosplenomegaly. Dysostosis multiplex was evident by age 2.5 years. Mitral and aortic valvular disease developed over the next few years and cardiac disease became the most important clinical problem. Foam cells were present in the bone marrow, and vacuolated lymphocytes were present in the peripheral blood smear. The patient had no neurologic symptoms, cherry red spots, or intellectual deterioration during the first 18 years. At age 16, aortic valve replacement for aortic regurgitation was performed.
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 it was known whether the disorder was clinically indistinguishable from the sialidoses without deficiency of beta-galactosidase, its distinctness was 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 GM1-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. Hoogeveen et al. (1981) showed that both enzyme activities could be restored by a 'corrective factor' of glycoprotein nature produced by normal fibroblasts and other mutant cells, including those of beta-galactosidase-deficient GM1-gangliosidosis. The form of deficiency of glycoprotein neuraminidase activity unassociated with beta-galactosidase deficiency (sialidosis I and mucolipidosis I) may have a defect in the structural gene for neuraminidase, whereas 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).
Sakuraba et al. (1985) pointed out that in normal subjects serum beta-galactosidase activity is markedly increased in clotting blood but patients with galactosialidosis show only a slight increase of this enzyme activity. Patients with GM1-gangliosidosis (230500) show no increase in enzyme in clotting blood. In normal individuals and persons with galactosialidosis, enzyme is released from leukocytes. Anticoagulants suppress this release.
Palmeri et al. (1986) found differences in the nature of the abnormality in 3 clinically distinct but presumably allelic forms of the disorder. In cells of the early-infantile type (usually associated with death soon after birth), the synthesis of the 52-kD precursor of the 32-kD 'protective protein' was markedly reduced. Absence of the latter protein explained the severe neuraminidase deficiency. In the juvenile-adult form, there was relatively more 52-kD precursor but no 32-kD protein could be detected. Cells of the late-infantile form had, besides a small amount of the 32-kD glycoprotein, an accumulation of the 52-kD precursor. Apparently, this protein was genetically altered in such a way that its further processing was impaired. In this mutant form, furthermore, treatment with leupeptin led to a 4- to 6-fold increase in residual neuraminidase activity and an increase of the 32-kD glycoprotein. Nanba et al. (1987) found that the protein concentrate of the culture medium of normal fibroblasts restored the activities of the deficient enzymes, beta-galactosidase and neuraminidase, in galactosialidosis cells. This effect was inhibited by an antiserum that recognized a 46-kD protein.
Galjart et al. (1988) determined that a 'protective protein' cDNA (CTSA) recognized a 2-kb mRNA in normal cells that was not evident in fibroblasts of an early infantile galactosialidosis patient.
Strisciuglio et al. (1988) demonstrated by immunoprecipitation experiments a reduced amount of the 32-kD 'protective protein' and a normal amount of its precursor in late infantile galactosialidosis fibroblasts, while neither of the 2 polypeptides were detectable in early infantile and juvenile/adult fibroblasts. They suggested from this and uptake studies that a block in the maturation of the protective protein is responsible for the late infantile type of galactosialidosis.
Kleijer et al. (1996) surveyed 20 galactosialidosis patients with different clinical phenotypes. They tested cathepsin A activity in cultured fibroblasts derived from the patients and their obligate heterozygote parents. In 12 patients with the early infantile type of the disease, almost complete absence of cathepsin A activity was observed, whereas 8 patients with either delayed infantile or the juvenile/adult type had 2% to 5% residual activity. Highest levels (5%) were present in 2 patients with milder clinical manifestations and later onset of the disease. Heterozygous values for cathepsin A were reduced on average to half of normal levels. They showed that cathepsin A has considerable activity in chorionic villi and amniocytes and was deficient in amniocytes from a pregnancy with an affected fetus, indicating the relevance of cathepsin A assay for prenatal diagnosis of galactosialidosis.
Landau et al. (1995) added galactosialidosis to the list of conditions that can cause nonimmune hydrops fetalis. Four pregnancies of a 22-year-old Bedouin woman produced a severely hydropic fetus in 1 case; her husband was a first cousin. The second pregnancy was terminated in the second trimester after ultrasound diagnosis of hydrops fetalis. The placenta showed marked accumulation of a mucoid material. The first and third pregnancies resulted in delivery of a preterm hydropic baby who died a few days after birth. During the fourth pregnancy, hydrops fetalis was diagnosed at 26 weeks. Following the spontaneous onset of labor at 32 weeks of gestation, a male hydropic baby was born by vaginal delivery. Physical examination showed massive ascites and edema of the limbs and genitalia. The face was notable for hematomata on the eyelids, coarse features, and a depressed nasal bridge. Both the liver and the spleen were palpable 4-5 cm below the costal margin. The infant was markedly hypotonic. Serum albumin was normal. Peritoneal drainage was performed twice during the first days of life. At 3 weeks of age, ascites reappeared, necessitating repeated peritoneal drainage. Thereafter, fluid continued to reaccumulate, and the infant died at 2 months of age following worsening respiratory neurologic status. Examination of the placenta showed the same mucoid material as was found in the placenta in the second pregnancy. Fibroblasts from a skin biopsy taken at 1 week of age showed no activity of sialidase and a low activity of beta-galactosidase, compatible with the diagnosis of galactosialidosis. A fifth pregnancy was monitored with chorionic villus sampling which at 10 weeks of gestation showed normal activity of both enzymes; the pregnancy ended in the delivery of a full-term healthy baby.
Olcay et al. (1998) described what appeared to be the first reported instance of cytopenias in galactosialidosis. The patient was a 7-month-old boy in whom the diagnosis of galactosialidosis had previously been made by enzymatic methods in both leukocytes and fibroblasts. He was later found to have anemia and thrombocytopenia and evidence of hemophagocytosis of erythrocytes, thrombocytes, lymphocytes, and granulocytes by the foamy cells that develop in this disorder.
Prenatal Diagnosis
Kleijer et al. (1979) made the prenatal diagnosis of galactosialidosis by measuring beta-galactosidase and neuraminidase activities in cultured amniotic fluid cells.
Halal et al. (1992), who referred to the enzyme deficient in this condition as carboxypeptidase-L, reported the case of a 14-year-old boy with ring chromosome 20. Decreased activity of carboxypeptidase-L/protective protein in cultured fibroblasts was demonstrated in this patient and in a patient with a different chromosomal rearrangement resulting in deletion of the distal segment of the long arm of chromosome 20. They interpreted these findings as indicating the assignment of the PPGB gene to the distal segment of 20q.
The transmission pattern of GSL in the families reported by Shimmoto et al. (1993) was consistent with autosomal recessive inheritance.
In a clinical and molecular analysis of 19 Japanese galactosialidosis patients from 15 unrelated families, Takano et al. (1991) found only 2 cases with generalized and severe manifestations of neonatal onset; the other 17 cases had late onset of neurologic manifestations. All 17 late-onset patients had a splice site mutation in the CTLA gene resulting in a deletion of exon 7 (613111.0002).
Shimmoto et al. (1993) reviewed a total of 6 mutations in Japanese patients with galactosialidosis. Many of the patients were genetic compounds and, as with other lysosomal storage diseases, compound heterozygosity of a mutation without expression of any enzyme activity, such as Y395C (613111.0006), with a mutation that produced a small amount of normally spliced mRNA, e.g., deletion of exon 7, resulted in clinical manifestations of intermediate severity.
Zhou et al. (1996) studied 8 patients with galactosialidosis who presented at different ages. All patients studied had PPCA mRNA. To identify the molecular lesions in the PPCA gene they used RT-PCR to amplify the entire coding sequence which was then sequenced. In the early-onset patients they detected 2 new mutations: val104 to met (613111.0009) and leu208 to pro (613111.0010). The second mutation present in one of the early-onset patients was gly411 to ser (613111.0011). A patient with juvenile/adult onset proved to be a compound heterozygote for a ser23-to-tyr mutation on one allele and a splice site mutation in intron 7 (613111.0002) on the other allele. The 5 patients with late infantile-onset galactosialidosis were genetically much more homogeneous, having either the phe412-to-val (613111.0001) or tyr221-to-asn (613111.0008) mutation. These mutations occurred either in the homozygous or compound heterozygous state and Zhou et al. (1996) considered them to be diagnostic for the late infantile phenotype. Zhou et al. (1996) determined that the main factor determining the clinical course in galactosialidosis patients is the lysosomal level of mutant PPCA. In 2 severely affected patients with early infantile onset, they identified 3 novel mutations, val104 to met, leu208 to pro, and gly411 to ser (613111.0011), that prevent the phosphorylation of the PPCA precursor and thereby its transport to the lysosome. Galactosialidosis patients with late infantile onset of disease had at least one allele that could be phosphorylated and transported to the lysosome. Zhou et al. (1996) noted that the met378-to-thr mutation (613111.0012), present in compound heterozygosity in one of the patients, represented the first example of a point mutation that generates a new asn-linked glycosylation site that is actually utilized. They noted further that the additional oligosaccharide chain likely affects the proper folding and compartmentalization of the mutant.
Ahern-Rindell et al. (1986, 1988) described a recessive disease in sheep with deficiency of both beta-galactosidase and alpha-neuraminidase. The ovine disease differed from human galactosialidosis in that heterozygotes showed an intermediate level of beta-galactosidase in fibroblasts whereas human heterozygotes show no gene dosage effect; further, incubation of affected ovine fibroblasts with the protease inhibitor leupeptin had no restoring effect on beta-galactosidase activity whereas it does in the case of the human disorder (Suzuki et al., 1981). Prieur et al. (1990) confirmed that the disorder in sheep is autosomal recessive. The lack of skeletal dysplasia in the ovine disease, which was predominantly neuronal suggested that it may not be homologous to galactosialidosis; furthermore, by kinetic complementation analysis of human and sheep fibroblasts, Ahern-Rindell et al. (1989) found results suggesting that the ovine mutation is homologous to the one causing GM1-gangliosidosis.
Prieur and Ahern-Rindell (1989) studied further an autosomal recessive lysosomal storage disease of sheep with deficiencies of lysosomal beta-galactosidase and alpha-neuraminidase. The clinical signs, lesions, and storage material resembled those of GM1-gangliosidosis, whereas the enzyme deficiencies resembled those of galactosialidosis. Fibroblasts from patients with 4 diseases, GM1-gangliosidosis, galactosialidosis, mucopolysaccharidosis type IVB, and mucolipidosis type II, showed no complementation with GM1-gangliosidosis or MPS IVb, whereas complementation did occur with the other 2 diseases. Thus, in this instance, the mutation appears to be in a structural gene for beta-galactosidase.
Suzuki (1997) stated that Suzuki et al. (1977) first clearly delineated galactosialidosis.
Ahern-Rindell, A. J., Murnane, R. D., Prieur, D. J. Interspecific genetic complementation analysis of human and sheep fibroblasts with beta-galactosidase deficiency. Somat. Cell Molec. Genet. 15: 525-533, 1989. [PubMed: 2512653] [Full Text: https://doi.org/10.1007/BF01534913]
Ahern-Rindell, A. J., Prieur, D. J., Murnane, R. D., Raghavan, S. S., Daniel, P. F., McCluer, R. H., Walkley, S. U., Parish, S. M. Inherited lysosomal storage disease associated with deficiencies of beta-galactosidase and alpha-neuraminidase in sheep. Am. J. Med. Genet. 31: 39-56, 1988. [PubMed: 3146925] [Full Text: https://doi.org/10.1002/ajmg.1320310108]
Ahern-Rindell, A. J., Prieur, D. J., Murnane, R. D. An inherited lysosomal storage disease of sheep associated with deficiencies of beta-galactosidase and alpha-neuraminidase. (Abstract) Am. J. Hum. Genet. 39: A3 only, 1986.
Andria, A., Strisciuglio, P., Pontarelli, G., Sly, W. S., Dodson, W. E. Infantile neuraminidase and beta-galactosidase deficiencies (galactosialidosis) with mild clinical courses.In: Tettamanti, G.; Durand, P.; Didonato, S. (eds.) : Perspectives in Inherited Metabolic Diseases. Vol. 4. Milan: Ermes (pub.) 1981. Pp. 379-395.
Berard-Badier, M., Adechy-Benkoel, L., Chamlian, A., Dubois-Gambarelli, D., Casanova, P., Mariani, A. Etude ultrastructurale du parenchyme hepatique dans les mucopolysaccharidoses. Path. Biol. (Paris) 18: 117-128, 1970. [PubMed: 4245330]
Chitayat, D., Applegarth, D. A., Lewis, J., Dimmick, J. E., McCormick, A. Q., Hall, J. G. Juvenile galactosialidosis in a white male: a new variant. Am. J. Med. Genet. 31: 887-901, 1988. [PubMed: 3149149] [Full Text: https://doi.org/10.1002/ajmg.1320310423]
d'Azzo, A., Andria, G., Strisciuglio, P., Galjaard, H. Galactosialidosis. In, Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic & Molecular Bases of Inherited Disease. Vol. III (8th ed.) New York: McGraw-Hill (pub.) 2001. P. 3811.
d'Azzo, A., Hoogeveen, A., Reuser, A. J. J., Robinson, D., Galjaard, H. Molecular defect in combined beta-galactosidase and neuraminidase deficiency in man. Proc. Nat. Acad. Sci. 79: 4535-4539, 1982. [PubMed: 6812049] [Full Text: https://doi.org/10.1073/pnas.79.15.4535]
Galjart, N. J., Gillemans, N., Harris, A., van der Horst, G. T. J., Verheijen, F. W., Galjaard, H., d'Azzo, A. Expression of a cDNA encoding the human 'protective protein' associated with lysosomal beta-galactosidase and neuraminidase: homology to yeast proteases. Cell 54: 755-764, 1988. [PubMed: 3136930] [Full Text: https://doi.org/10.1016/s0092-8674(88)90999-3]
Goldberg, M. F., Cotlier, E., Fichenscher, L. G., Kenyon, K. R., Enat, R., Borowsky, S. A. Macular cherry-red spot, corneal clouding, and beta-galactosidase deficiency: clinical, biochemical, and electron microscopic study of a new autosomal recessive storage disease. Arch. Intern. Med. 128: 387-398, 1971. [PubMed: 4999185]
Halal, F., Chitayat, D., Parikh, H., Rosenblatt, B., Tranchemontagne, J., Vekemans, M., Potier, M. 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. Am. J. Med. Genet. 43: 576-579, 1992. [PubMed: 1605251] [Full Text: https://doi.org/10.1002/ajmg.1320430314]
Hoeksema, H. L., de Wit, J., Westerveld, A. The genetic defect in the various types of human beta-galactosidase deficiency. Hum. Genet. 53: 241-247, 1980. [PubMed: 6766901] [Full Text: https://doi.org/10.1007/BF00273505]
Hoogeveen, A., d'Azzo, A., Brossmer, R., Galjaard, H. Correction of combined beta-galactosidase/neuraminidase deficiency in human fibroblasts. Biochem. Biophys. Res. Commun. 103: 292-299, 1981. [PubMed: 6797429] [Full Text: https://doi.org/10.1016/0006-291x(81)91692-2]
Hoogeveen, A. T., Verheijen, F. W., d'Azzo, A., Galjaard, H. Genetic heterogeneity in human neuraminidase deficiency. Nature 285: 500-502, 1980. [PubMed: 6772959] [Full Text: https://doi.org/10.1038/285500a0]
Ishibashi, A., Tsuboi, R., Shinmei, M. Beta-galactosidase and neuraminidase deficiency associated with angiokeratoma corporis diffusum. Arch. Derm. 120: 1344-1346, 1984. [PubMed: 6435542]
Kleijer, W. J., Geilen, G. C., Janse, H. C., Van Diggelen, O. P., Zhou, X. Y., Galjart, N. J., Galjaard, H., D'Azzo, A. Cathepsin A deficiency in galactosialidosis: studies of patients and carriers in 16 families. Pediat. Res. 39: 1067-1071, 1996. [PubMed: 8725271] [Full Text: https://doi.org/10.1203/00006450-199606000-00022]
Kleijer, W. J., Hoogeveen, A., Verheijen, F. W., Niermeijer, M. F., Galjaard, H., O'Brien, J. S., Warner, T. G. Prenatal diagnosis of sialidosis with combined neuraminidase and beta-galactosidase deficiency. Clin. Genet. 16: 60-61, 1979. [PubMed: 477017] [Full Text: https://doi.org/10.1111/j.1399-0004.1979.tb00851.x]
Landau, D., Zeigler, M., Shinwell, E. S., Meisner, I., Bargal, R. Hydrops fetalis in four siblings caused by galactosialidosis. Isr. J. Med. Sci. 31: 321-322, 1995. [PubMed: 7759227]
Li, Y.-T., Muhiudeen, I. A., DeGasperi, R., Hirabayashi, Y., Li, S.-C. Presence of activator proteins for the enzymic hydrolysis of GM1 and GM2 gangliosides in normal human urine. Am. J. Hum. Genet. 35: 629-634, 1983. [PubMed: 6881139]
Loonen, M. C. B., Reuser, A. J. J., Visser, P., Arts, W. F. M. Combined sialidase (neuraminidase) and beta-galactosidase deficiency: clinical, morphological and enzymological observations in a patient. Clin. Genet. 26: 139-149, 1984. [PubMed: 6432381] [Full Text: https://doi.org/10.1111/j.1399-0004.1984.tb00804.x]
Lowden, J. A., O'Brien, J. S. Sialidosis: a review of human neuraminidase deficiency. Am. J. Hum. Genet. 31: 1-18, 1979. [PubMed: 107795]
Maire, I., Nivelon-Chevallier, A. Combined deficiency of beta-galactosidase and neuraminidase: three affected siblings in a French family. J. Inherit. Metab. Dis. 4: 221-223, 1981. [PubMed: 6796775] [Full Text: https://doi.org/10.1007/BF02263656]
Mueller, O. T., Shows, T. B. Human beta-galactosidase and alpha-neuraminidase deficient mucolipidosis: genetic complementation analysis of the neuraminidase deficiency. Hum. Genet. 60: 158-162, 1982. [PubMed: 7076257] [Full Text: https://doi.org/10.1007/BF00569704]
Nanba, E., Tsuji, A., Omura, K., Suzuki, Y. Galactosialidosis: direct evidence that a 46-kilodalton protein restores deficient enzyme activities in fibroblasts. Biochem. Biophys. Res. Commun. 144: 138-142, 1987. [PubMed: 3107551] [Full Text: https://doi.org/10.1016/s0006-291x(87)80486-2]
Olcay, L., Gumruk, F., Boduroglu, K., Coskun, T., Tuncbilek, E. Anaemia and thrombocytopenia due to haemophagocytosis in a 7-month-old boy with galactosialidosis. J. Inherit. Metab. Dis. 21: 679-680, 1998. [PubMed: 9762607] [Full Text: https://doi.org/10.1023/a:1005444903597]
Palmeri, S., Hoogeveen, A. T., Verheijen, F. W., Galjaard, H. Galactosialidosis: molecular heterogeneity among distinct clinical phenotypes. Am. J. Hum. Genet. 38: 137-148, 1986. [PubMed: 3080874]
Prieur, D. J., Ahern-Rindell, A. J., Murnane, R. D., Wright, R. W., Parish, S. M. Inheritance of an ovine lysosomal storage disease associated with deficiencies of beta-galactosidase and alpha-neuraminidase. J. Hered. 81: 245-249, 1990. [PubMed: 2125614] [Full Text: https://doi.org/10.1093/oxfordjournals.jhered.a110986]
Prieur, D. J., Ahern-Rindell, A. J. 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) Am. J. Hum. Genet. 45 (suppl.): A213 only, 1989.
Sakuraba, H., Iimori, Y., Suzuki, Y., Kint, J. A., Akagi, M. Galactosialidosis: low beta-galactosidase activity in serum after long-term clotting. Ann. Neurol. 18: 261-263, 1985. [PubMed: 3929673] [Full Text: https://doi.org/10.1002/ana.410180215]
Shimmoto, M., Fukuhara, Y., Itoh, K., Oshima, A., Sakuraba, H., Suzuki, Y. Protective protein gene mutations in galactosialidosis. J. Clin. Invest. 91: 2393-2398, 1993. [PubMed: 8514852] [Full Text: https://doi.org/10.1172/JCI116472]
Strisciuglio, P., Creek, K. E., Sly, W. S. Complementation, cross-correction, and drug correction studies of combined beta-galactosidase-neuraminidase deficiency in human fibroblasts. Pediat. Res. 18: 167-171, 1984. [PubMed: 6422434] [Full Text: https://doi.org/10.1203/00006450-198402000-00011]
Strisciuglio, P., Parenti, G., Giudice, C., Lijoi, S., Hoogeveen, A. T., d'Azzo, A. The presence of a reduced amount of 32-kD 'protective' protein is a distinct biochemical finding in late infantile galactosialidosis. Hum. Genet. 80: 304-306, 1988. [PubMed: 3142815] [Full Text: https://doi.org/10.1007/BF01790104]
Strisciuglio, P., Sly, W. S., Dodson, W. E., McAlister, W. H., Martin, T. C. 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. Am. J. Med. Genet. 37: 573-577, 1990. [PubMed: 2148053] [Full Text: https://doi.org/10.1002/ajmg.1320370431]
Suzuki, Y., Nakamura, N., Fukuoka, K., Shimada, Y., Uono, M. Beta-galactosidase deficiency in juvenile and adult patients: report of six Japanese cases and review of literature. Hum. Genet. 36: 219-229, 1977. [PubMed: 404231] [Full Text: https://doi.org/10.1007/BF00273261]
Suzuki, Y., Nakamura, N., Shimada, Y., Yotsumoto, H., Endo, H., Nagashima, K. 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. Arch. Neurol. 34: 157-161, 1977. [PubMed: 402903] [Full Text: https://doi.org/10.1001/archneur.1977.00500150043008]
Suzuki, Y., Sakuraba, H., Hayasi, K., Suzuki, K., Imahori, K. Beta-galactosidase-neuraminidase deficiency: restoration of beta-galactosidase activity by protease inhibitors. J. Biochem. 90: 271-273, 1981. [PubMed: 6793566] [Full Text: https://doi.org/10.1093/oxfordjournals.jbchem.a133462]
Suzuki, Y., Sakuraba, H., Potier, M., Akagi, M., Sakai, M., Beppu, H. Beta-galactosidase-neuraminidase deficiency in adults: deficiency of a freeze-labile neuraminidase in leukocytes and fibroblasts. Hum. Genet. 58: 387-389, 1981. [PubMed: 7327559] [Full Text: https://doi.org/10.1007/BF00282820]
Suzuki, Y. Personal Communication. Tokyo, Japan 8/7/1997.
Takano, T., Shimmoto, M., Fukuhara, Y., Itoh, K., Kase, R., Takiyama, N., Kobayashi, T., Oshima, A., Sakuraba, H., Suzuki, Y. Galactosialidosis: clinical and molecular analysis of 19 Japanese patients. Brain Dysfunction 4: 271-280, 1991.
Thomas, G. H., Goldberg, M. F., Miller, C. S., Reynolds, L. W. Neuraminidase deficiency in the original patient with the Goldberg syndrome. Clin. Genet. 16: 323-330, 1979. [PubMed: 519904] [Full Text: https://doi.org/10.1111/j.1399-0004.1979.tb01010.x]
Wenger, D. A., Tarby, T. J., Wharton, C. Macular cherry-red spots and myoclonus with dementia: coexistent neuraminidase and beta-galactosidase deficiencies. Biochem. Biophys. Res. Commun. 82: 589-595, 1978. [PubMed: 96839] [Full Text: https://doi.org/10.1016/0006-291x(78)90915-4]
Yamamoto, A., Adachi, A., Kawamura, S., Takahashi, M., Kitani, T., Ohtori, T., Shinji, Y., Nishikawa, M. Localized beta-galactosidase deficiency: occurrence in cerebellar ataxia with myoclonus epilepsy and macular cherry-red spot--a new variant of Gm-1-gangliosidosis? Arch. Intern. Med. 134: 627-634, 1974. [PubMed: 4278184] [Full Text: https://doi.org/10.1001/archinte.134.4.627]
Yamano, T., Shimada, M., Sugino, H., Dezawa, T., Koike, M., Okada, S., Yabuuchi, H. Ultrastructural study on a severe infantile sialidosis (beta-galactosidase-alpha-neuraminidase deficiency). Neuropediatrics 16: 109-112, 1985. [PubMed: 3925363] [Full Text: https://doi.org/10.1055/s-2008-1052553]
Zhou, X.-Y., van der Spoel, A., Rottier, R., Hale, G., Willemsen, R., Berry, G. T., Strisciuglio, P., Morrone, A., Zammarchi, E., Andria, G., d'Azzo, A. Molecular and biochemical analysis of protective protein/cathepsin A mutations: correlation with clinical severity in galactosialidosis. Hum. Molec. Genet. 5: 1977-1987, 1996. Note: Erratum: Hum. Molec. Genet. 6: 146 only, 1997. [PubMed: 8968752] [Full Text: https://doi.org/10.1093/hmg/5.12.1977]