Mannosidosis: Clinical, Morphologic, Immunologic, and Biochemical Studies

Desnick, Robert J.; Sharp, Harvey L.; Grabowski, Gregory A.; Brunning, Richard D.; Quie, Paul G.; Sung, Joo Ho; Gorlin, Robert J.; Ikonne, J. U.

doi:10.1203/00006450-197612000-00008

Cited by 105 publications

(63 citation statements)

References 19 publications

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“…§ Acidic α -mannosidase is 3.3% and 10.3% of the control values in lymphocytes and cultured fibroblasts, respectively (present article). At 2.0 mM, as reported by others, 16 these values are 2.9% and 7.8%.…”

Section: Discussionsupporting

confidence: 68%

“…The acidic mannosidase, 16 neutral mannosidase, 16 and ß-mannosidase 17 were measured with some modifications of the reported procedures. The incubation conditions for acidic mannosidase were sodium citrate-phosphate 100 mmol/L, pH 4.4, zinc sulfate 2.5 mmol/L, sodium nitrate 0.2 mg/mL, 4-methylumbelliferyl α-mannoside 0.25 to 3.0 mmol/L, and cell protein 75 μg/ mL in 20 μL; the incubation time was 15 minutes at 37°C.…”

Section: Methodsmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 68%

Section: Methodsmentioning

confidence: 99%

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

et al. 1989

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“…Similarly in hepatocytes derived from a child with α-mannosidosis (Gordon et al 1980), mitochondria were abnormal with respect to their size and shape, however, their internal structure was not changed. In contrast to our results on fibroblasts and Gordon et al (1980) on hepatocytes, two other studies did not report any mitochondrial changes at ultrastructure level in α-mannosidosis patients either on hepatocytes or brain tissue obtained at autopsy (Desnick et al 1976;Autio et al 1982). Unfortunately, mutation types were not described in these patients.…”

Section: Discussioncontrasting

confidence: 55%

Ultrastructural and functional abnormalities of mitochondria in cultivated fibroblasts from α-mannosidosis patients

et al. 2009

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α-Mannosidosis is a lysosomal storage disorder caused by α-mannosidase deficiency. Clinical course of the disease ranges from severe infantile to milder juvenile type and includes mental retardation, skeletal deformities, coarse facies, hepatomegaly and hearing loss. The aim of the study was to analyse mitochondrial ultrastructure and function in cultivated fibroblasts from three patients with α-mannosidosis. All patients were homozygous for the c.2248C>T mutation in the MAN2B1 gene encoding lysosomal α-mannosidase. The mutation results in incorrect protein folding and severe decrease of α-mannosidase activity. The misfolded protein is retained by the control system of endoplasmic reticulum (ER). In analysed fibroblasts, we observed dilated ER, higher amount of aberrant mitochondria and reduced mitochondrial mass compared to controls. Respiratory chain complex IV, cytochrome c oxidase (COX), activity and the ratio between COX and citrate synthase (control enzyme) were significantly increased in comparison to controls (P < 0.05). Furthermore, the activity at least from one of other respiratory chain complexes was increased in each studied cell line. Mitochondrial membrane potential as well as reactive oxygen species production were comparable with controls. Based on our results, we hypothesize more profound effect of swelled and damaged mitochondria and ER dilatation on tissues with higher energy demand than fibroblasts have.

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“…However the Km value for the activity in one of the patients in which crossreacting material was detected was not significantly different from that of the control [ 171. It has been claimed in other cases that the residual a-D-mannosidase is activated 6-lo-fold by Zn2' [ 181 or that the value of Km is decreased by Co'+ [7]. In our case the mutant enzyme is only activated by 20% by Zn2+ over a wide range of concentration and is inhibited by Co*+ (unpublished results).…”

Section: Discussionmentioning

confidence: 61%

Evidence that the mutant enzyme in fibroblasts of a patient with mannosidosis does not crossreact with antiserum raised against normal acidic α‐D‐mannosidase

Burditt¹,

Chotai²,

G³

1978

FEBS Letters

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Mannosidosis: Clinical, Morphologic, Immunologic, and Biochemical Studies

Cited by 105 publications

References 19 publications

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

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

Ultrastructural and functional abnormalities of mitochondria in cultivated fibroblasts from α-mannosidosis patients

Evidence that the mutant enzyme in fibroblasts of a patient with mannosidosis does not crossreact with antiserum raised against normal acidic α‐D‐mannosidase

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