α‐<i>N</i>‐acetylgalactosaminidase deficiency, a new lysosomal storage disorder

Diggelen, O. P. van; Schindler, Detlev; Willemsen, Rob; Boer, M.; Kleijer, Wim J.; Huijmans, J. G. M.; Blom, W.; Galjaard, H.

doi:10.1007/bf01800424

Cited by 45 publications

(13 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pattern was comparable to that of the first patients with a-NAGA deficiency. 11 At the age of 12 months his neuromotor development was slightly delayed, which became more prominent in the next 2 years. At 3 years old he was unable to walk without support but hand co-ordination and speech development was normal.…”

Section: Methodsmentioning

confidence: 99%

Human α-N-acetylgalactosaminidase (α-NAGA) deficiency: no association with neuroaxonal dystrophy?

Vreken

et al. 2001

Eur J Hum Genet

View full text Add to dashboard Cite

Two new individuals with a-NAGA deficiency are presented. The index patient, 3 years old, has congenital cataract, slight motor retardation and secondary demyelinisation. Screening of his sibs revealed an a-NAGA deficiency in his 7-year-old healthy brother who had no clinical or neurological symptoms. Both sibs are homozygous for the E325K mutation, the same genotype that was found in the most severe form of a-NAGA deficiency presenting as infantile neuroaxonal dystrophy. Thus, at the age of 7 years the same genotype of a-NAGA may present as a`non-disease' (present healthy case) and can be associated with the vegetative state (the first two patients described with a-NAGA deficiency). The clinical heterogeneity among the 11 known individuals with a-NAGA deficiency is extreme, with a`non-disease' (two cases) and infantile neuroaxonal dystrophy (two cases) at the opposite sides of the clinical spectrum. The broad spectrum is completed by a very heterogeneous group of patients with various degrees of epilepsy/behavioural difficulties/psychomotor retardation (four patients) and a mild phenotype in adults without overt neurological manifestations who have angiokeratoma and clear vacuolisation in various cell types (three cases). These observations are difficult to reconcile with a straightforward genotype-phenotype correlation and suggest that factors or genes other than a-NAGA contribute to the clinical heterogeneity of the 11 patients with a-NAGA deficiency.

show abstract

Section: Methodsmentioning

confidence: 99%

Human α-N-acetylgalactosaminidase (α-NAGA) deficiency: no association with neuroaxonal dystrophy?

Vreken

et al. 2001

Eur J Hum Genet

View full text Add to dashboard Cite

show abstract

“…Previously, an infantile form of neuroaxonal dystrophy due to the deficient activity of lysosomal a-GalNAc was described in two consanguineous German boys (4)(5)(6)(7). The course of this disorder was remarkably distinct from that of the adult-onset form, and was characterized by normal development until 8-12 mo of life, followed by a rapidly regressive course resulting in profound psychomotor retardation by three years of age.…”

Section: Introductionmentioning

confidence: 99%

The molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes angiokeratoma corporis diffusum with glycopeptiduria.

Wang¹,

Kanzaki²,

Desnick³

1994

J. Clin. Invest.

View full text Add to dashboard Cite

roaxonal dystrophy * lysosomal storage disease * a-N-acetylgalactosaminidase -mutation analysis * transient expression Angiokeratoma corporis diffusum with glycopeptiduria is a recently recognized inborn error of glycoprotein catabolism resulting from the deficient activity of human a-N-acetylgalactosaminidase (E.C.3.2.1.49; a-GalNAc). The first patient with this autosomal recessive disorder, a 46-yr-old consanguineous Japanese woman, presented with diffuse angiokeratoma, mild intellectual impairment, and peripheral neuroaxonal degeneration. Deficient a-GaINAc activity also has been reported in consanguineous brothers with an infantileonset form of neuroaxonal dystrophy resulting from a missense mutation (designated E325K) in the a-GaINAc gene. To identify the mutation causing the phenotypically distinct adult-onset disorder, Southern and Northern hybridization analyses of DNA and RNA from the affected homozygote were performed which revealed a grossly normal a-GalNAc gene structure and normal transcript size and abundancy. Reverse transcription, amplification, and sequencing of the a-GalNAc transcript identified a single C to T transition at nucleotide (nt) 985 that predicted an arginine to tryptophan substitution in residue 329 (designated R329W) of the aGaINAc polypeptide. This base substitution was confirmed by hybridization of PCR-amplified genomic DNA from family members with allele-specific oligonucleotides. Transient expression of an a-GalNAc construct containing the R329W mutation resulted in the expression of an immunoreactive polypeptide which had no detectable a-GalNAc activity.Comparison of the biosynthesis and stabilities of the transiently expressed and radiolabeled normal, E325K (infantile-onset) and R329W (adult-onset) a-GalNAc polypeptides in COS-1 cells indicated that both the mutant precursors were processed to the mature form; however, the E325K mutant polypeptide was more rapidly degraded than the R329W subunit, thereby providing a basis for the distinctly different infantile-and adult-onset phenotypes. (J. Clin. Invest. 1994. 94:839-845.)

show abstract

“…In lane 1 of the figure the abnormal oligosaccharide pattern of a patient with N-acetylgalactosaminidase deficiency is shown. This new lysosomal storage disease was recently described in detail (Van Diggelen et al, 1988). The desalting procedure with ion-exchange resins does not work in aspartylglycosylami-nase deficiency because the accumulating aspartylglucosamine is bound to the cation-exchange resin but the aspartylglucosamine can easily be detected with amino acid analysis.…”

Section: Mono-and Disaccharidesmentioning

confidence: 97%

A clinical biochemist's view of the investigation of suspected inherited metabolic disease

Blom

Huijmans

Berg

1989

J of Inher Metab Disea

Self Cite

View full text Add to dashboard Cite

The necessity for a multi-disciplinary approach to the study of genetic disease is discussed. The progress of laboratory investigation programmes made it not feasible and inefficient to run a full metabolic investigation programme in every new patient suspected of inherited metabolic disease. An application form for metabolic investigation is described, which can be used to collect clinical information relevant to metabolic disease. On the basis of the patient's clinical information, selection criteria are given to decide which laboratory investigation programme has to be performed in the individual patient. A full metabolic laboratory investigation programme is described and illustrated with some examples of abnormal metabolite patterns. Diagnostic results over a 2-year period are presented.

show abstract

α‐N‐acetylgalactosaminidase deficiency, a new lysosomal storage disorder

Cited by 45 publications

References 21 publications

Human α-N-acetylgalactosaminidase (α-NAGA) deficiency: no association with neuroaxonal dystrophy?

Human α-N-acetylgalactosaminidase (α-NAGA) deficiency: no association with neuroaxonal dystrophy?

The molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes angiokeratoma corporis diffusum with glycopeptiduria.

A clinical biochemist's view of the investigation of suspected inherited metabolic disease

Contact Info

Product

Resources

About