Excretion of mannose-rich complex carbohydrates by a patient with α-mannosidase deficiency (mannosidosis)

Tsay, Grace Chen; Dawson, Glyn; Matalon, Reuben

doi:10.1016/s0022-3476(74)80768-7

Cited by 36 publications

(15 citation statements)

References 8 publications

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“…7). In other cases, however, residual acidic activity was detected by electrophoresis only when using much higher protein concentrations (17). These results, plus the 4-to 5-fold increase of the apparent K,, suggest a mutation of the a-mannosidase gene yielding a defective protein with different in vitro properties than previously reported.…”

Section: Discussionmentioning

confidence: 44%

“…Since the initial description of mannosidosis in 1967 (14), the biochemistry of this disorder has been characterized in several laboratories (1)(2)(3)(9)(10)(11)(12)(13)(14)(15)(16)(17). Heterogeneity has been observed in both the clinical severity and the biochemistry of this entity.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, this deduction is based on in vitro studies using a synthetic substrate. The observation that Znf+ causes a 40% stimulation of acidic a-mannosidase activity in the patients' cells agrees with previous findings and may be of significance in the treatment of such cases.Mannosidosis, a deficiency of the acidic form of a-mannosidase (EC 3.3.1.24) (14, 15), results in the accumulation of mannose-rich glycosylated compounds in the lysosomes of various tissues (1,12,15) and the excretion of similar compounds in the urine (13,17,18). Clinically, the disorder presents with mildly coarse facies, mild hepatosplenomegaly, skeletal changes, and psychomotor retardation.…”

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confidence: 99%

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A New Variant of Mannosidosis with Increased Residual Enzymatic Activity and Mild Clinical Manifestation

Bach

Kohn

Lasch³

et al. 1978

Pediatr Res

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SummaryA partial deficiency of a-mannosidase was found in cultured skin fibroblasts, serum, and extracts of leukocytes in two siblings with mild mental retardation, delayed speech, a suggestion of coarse or full facies, and limited mobility of the large joints. All other lysosomal enzymes tested were within the normal range. Their father demonstrated intermediate a-mannosidase activity. The addition of 2 mM Zn++ caused a 40% increase of the amannosidase activity in cell extracts of both patients and control subjects. pH profiles and Cellogel electrophoresis of the patients' cells indicated 20% residual activity of the acidic a-mannosidase isoenzyme (pH optimum at 4.0), whereas the activity of the isozyme with pH optimum of 6.0 was normal. Increasing substrate concentration (1-10 mM) demonstrated a 4to 5-fold increase in the a~~a r e n t K, of the acidic a-mannosidase in the patients' fibrobiasts. This residual activity, however, was apparently not sufficient for the normal catabolism of mannose-containing molecules, since electron microscopic examination of the culture; fibroblasts demonstrated numerous lysosomal storage bodies. SpeculationThis family supports the concept that mannosidosis is not a homogeneous syndrome but manifests clinical as well as biochemical heterogeneity. The partial activity of acidic a-mannosidase observed in the cultured fibroblasts (approximately 20%) was insufficient for normal catabolism and allows accumulation of amannoside-containing substrates leading to the abnormal phenctype. Nevertheless, this deduction is based on in vitro studies using a synthetic substrate. The observation that Znf+ causes a 40% stimulation of acidic a-mannosidase activity in the patients' cells agrees with previous findings and may be of significance in the treatment of such cases.Mannosidosis, a deficiency of the acidic form of a-mannosidase (EC 3.3.1.24) (14, 15), results in the accumulation of mannose-rich glycosylated compounds in the lysosomes of various tissues (1,12,15) and the excretion of similar compounds in the urine (13,17,18). Clinically, the disorder presents with mildly coarse facies, mild hepatosplenomegaly, skeletal changes, and psychomotor retardation. Human a-mannosidase is separable into two distinct isoenzymes in fibroblasts (16) and three distinct isoenzymes in liver (7). In the liver, two isoenzymes, supposedly lysosomal, have acidic optimal activity (pH 4.0-4.5), whereas the third, a nonlysosomal component, is optimally active at pH 6.0 (7). Patients with mannosidosis demonstrate either a complete deficiency or reduced activity of the acidic isoenzymes. Structural changes in the acidic isoenzyme demonstrate a 25-to 50-fold increase in apparent K, values and high susceptibility to heat inactivation 10 (4, 6, 8), whereas neutral a-mannosidase is normal (7, 11). The normal neutral a-mannosidase activity may explain the differing residual enzyme activities in various tissues of these patients. We wish to describe a family whose clinical and biochemical findings suggest a new variant of ...

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Section: Discussionmentioning

confidence: 44%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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A New Variant of Mannosidosis with Increased Residual Enzymatic Activity and Mild Clinical Manifestation

Bach

Kohn

Lasch³

et al. 1978

Pediatr Res

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“…Since Ockerman's original report in 1967 (33), only 18 patients with this lysosomal storage disease have been described (I, 2,6,14,24,26,27,32,46). We have seen five patients in two unrelated families at the University of Minnesota Hospitals during the past 4 years.…”

Section: Speculationmentioning

confidence: 98%

“…Our studies demonstrate that the enzymatic diagnosis of suspect homozygotes can be made reliably using plasma, isolated leukocytes, or cultured skin fibroblasts assayed carefully at the appropriate acidic pH ( Table 2). The recent demonstration that total urinary mannose may be unreliable because of the wide variability in glycoprotein excretion in normal individuals (46) underscores the necessity for measurement of acidic a-mannosidase activities rather than the levels of urinary mannose (32,33).…”

Section: Effect O F D H and Substratementioning

confidence: 99%

Mannosidosis: Clinical, Morphologic, Immunologic, and Biochemical Studies

et al. 1976

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Mannosidosis

Kistler¹,

Lott²,

Kolodny³

et al. 1977

Arch Neurol

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Mannosidosis is a rare inborn error of metabolism characterized by deficiency of the lysosomal enzyme alpha-mannosidase and widespread storage of complex carbohydrate, which is enriched in mannose. Two affected unrelated males, aged 6 and 26 years, are reported. Both had a nonprogressive encephalopathy with moderately severe mental retardation. The older patient showed several unique features, including massive gingival hyperplasia associated with histiocytes containing large amounts of a material with the staining characteristics of glycoprotein. The best determinant of mannose storage proved to be the ratio of mannose to other carbohydrates in urinary polysaccharides. The enzyme deficiency in this disease is most convincingly demonstrated at pH values below 4.0. The ability of zinc to activate the mutant enzyme in vitro offers a possible mode of therapy for this disease. Retarded individuals with a Hurler-like appearance and gum hyperplasia of unknown cause should be screened for alpha-mannosidase deficiency.

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Excretion of mannose-rich complex carbohydrates by a patient with α-mannosidase deficiency (mannosidosis)

Cited by 36 publications

References 8 publications

A New Variant of Mannosidosis with Increased Residual Enzymatic Activity and Mild Clinical Manifestation

A New Variant of Mannosidosis with Increased Residual Enzymatic Activity and Mild Clinical Manifestation

Mannosidosis: Clinical, Morphologic, Immunologic, and Biochemical Studies

Mannosidosis

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