Mannosidosis: Clinical, Fine‐structural and Biochemical Findings in Three Cases

Auti, Seppo; Nordén, Nils E.; Öckerma, Per-Arne; Riekkine, Paavo; Rapol, Juhani; Louhim, Tuula

doi:10.1111/j.1651-2227.1973.tb17065.x

Cited by 60 publications

(18 citation statements)

References 16 publications

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“…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%

“…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.…”

Section: Speculationmentioning

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: 99%

Section: Speculationmentioning

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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“…Cerebrospinal fluid content of protein and glucose were reported as normal in one case. 19 In our patient, these studies were normal. No chromosomal abnormalities could be found in four previously reported cases, 4,19 as well as in ours.…”

Section: Discussionmentioning

confidence: 83%

“…This pattern of accelerated, then diminished physical growth had been observed in other patients. 4,[18][19][20][21] In mannosidosis, mannose-containing oligosaccharides accumulate in the brain. 2 Data on both brain autopsy and CT scan are scanty.…”

Section: Discussionmentioning

confidence: 99%

Mannosidosis in a Sudanese Child: Report of a Case with Review of the Literature

et al. 1989

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MA Abdullah, PT Ozand, M Al-Nasser, S Meshhadani, Mannosidosis in a Sudanese Child: Report of a Case with Review of The Literature. 1989; 9(1): 82-87 Mannosidosis is an autosomal recessive glycoprotein storage disease described by Ockerman 1 and caused by a deficiency of lysosomal isozymes (A and B) of α-D-mannosidase. 2 The clinical and pathological changes occurring during the course of the disease have recently been summarized. [3][4][5] Biochemical verification of the diagnosis requires proof of mannosidase deficiency and analysis of the urinary mannose-containing oligosaccharides. [3][4][5] Most of the cases have been reported from Europe and the United States. Apart from one family report, 6 we are not aware of case reports from Africa or the Middle East. This is a report of a Sudanese child whom we recently encountered. Case ReportA 16-month-old Sudanese boy was the offspring of healthy consanguineous Sudanese parents of Arab-Nubian origin. He had two other normal siblings and was the product of a normal pregnancy and normal spontaneous vaginal delivery. Growth and development had apparently been normal until the age of 4 months, when his problems started as severe wheezing which was later diagnosed as bronchial asthma.When first seen by us at the age of 5 months, he had a head circumference above the 97th percentile, but there was no clinical evidence of increased intracranial pressure; both his height and weight were above the 90th percentile. He was labeled as developmentally normal for his age. At this time a CT scan of the brain showed evidence of cerebral atrophy and ventricular dilatation (Figure 1). The x-ray film of his wrist was reported as showing mild rickets which could not be documented biochemically. The patient was readmitted at the age of 16 months with severe bronchial asthma and pneumonia. On this occasion, both his parents and his doctors were concerned about his delayed development. He was developmentally assessed as follows: personal 8/16, fine motor 12/16, gross motor 4/16, and language 10/16 months. Physical examination otherwise showed coarse Hurler's-like facies with flat nasal bridge, mandibular prognathism, prominent epicanthic folds, and prominent tongue. There were bilateral spotty whitish corneal opacities with markedly bluish and darkly pigmented scleral spots. There were no lenticular opacities, and the intraocular pressure as well as the funduscopy were normal. His skin showed many large bluish mongolian-spot-like areas all over the body. Heart showed clinical evidence of cardiomegaly and grade 3/6 murmur of mitral regurgitation with cardiac decompensation needing treatment. There was hepatomegaly of 4 cm with no splenomegaly as confirmed by ultrasound. He was hypotonic and had lumbar lordosis. He was not deaf. There were no joint contractures. At this admission, his height and head circumference were below the 90th percentile while his height was at the 50th percentile.Skeletal survey showed evidence of dysostosis multiplex with no evidence of rickets (Figure 2). A re...

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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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Mannosidosis: Clinical, Fine‐structural and Biochemical Findings in Three Cases

Cited by 60 publications

References 16 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 in a Sudanese Child: Report of a Case with Review of the Literature

Mannosidosis

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