Consultations & Comments

June 1, 2007

I believe the classification scheme and the biochemical pathways proposed for oligosaccharidoses outlined in a recent case on Hunter syndrome are both misleading and out of date.

I believe the classification scheme and the biochemical pathways proposed for oligosaccharidoses outlined in a recent case on Hunter syndrome1 are both misleading and out of date.

The traditional classification of lysosomal storage diseases is based on the dominant storage material within the lysosome. There is broad overlap of the clinical features of some classes; in the context of this article, the presence of dysostosis multiplex and organomegaly in the 3 disorders mentioned lead to the misclassification of these disorders as oligosaccharidoses. GM1 gangliosidosis is a sphingolipidosis, and I (inclusion)-cell disease and sialidoses are mucolipidoses.

I-cell disease has a complex storage product and a unique biochemical mechanism. Oligosaccharidoses are now classified as glycoproteinoses and include the mannosidoses, fucosidosis, aspartylglucosaminuria, and Schindler disease.2 The cherry red spot is a feature of many sphingolipidoses.3

There are over 40 lysosomal storage disorders; they are individually rare, but in aggregate are found in a minimum of 1 in 5000 people. They are very complicated clinically and biochemically. The single most important management approach for children and adults with these disorders is referral to centers with broad (multispecialty) expertise and experience in lysosomal storage disorders.

The authors cite an article on mutation analysis in Hunter syndrome4 that is unrelated to the topic for which it is cited.

---- Lawrence Charnas, MD, PhD
Associate Professor of Pediatrics
University of Minnesota

We appreciate the information on lysosomal storage diseases provided by Dr Charnas and agree that multispecialty center referral is crucial for these complex and chronic conditions. Our case emphasized recognition, rather than details that are better addressed in specialty journals--hence our inclusion of 2 references4,5 as overviews of clinical and molecular delineation.

Use of the broad term "oligosaccharidoses" emphasized that negative results of urine mucopolysaccharide (glycosaminoglycan) testing should not delay referral of children with Hunter-like symptoms. Residual chains of modified sugars (oligosaccharides) from inadequate degradation of glycolipids or glycoproteins may be present in each of the disorders mentioned by Dr Charnas and detected by a different urine screen.

We favor the approach outlined by Thomas6 in referring to this group (now 10 diseases) as disorders of glycoprotein degradation and would remind readers that there is no "mucolipid" storage material.

---- Golder N. Wilson, MD, PhD
Clinical Professor of Pediatrics
Texas Tech University Health Sciences Center
KinderGenome Pediatric Genetics
Amarillo

References:

REFERENCES:


1.

Habiba NM, Boger JA, Wilson GN. Hunter syndrome.

Consultant For Pediatricians.

2007;6:149-152.

2.

Platt F, Walkley S. Lysosomal defects and storage.

Lysosomal Disorders of the Brain.

In: Platt F, Walkley S, eds. Oxford, UK: Oxford University Press; 2004:32-49.

3.

Wraith J. Clinical aspects and diagnosis. In: Platt F, Walkley S, eds.

Lysosomal Disorders of the Brain.

Oxford, UK: Oxford University Press; 2004:50-77.

4.

Froissart R, Maire I, Millat G, et al. Identification of iduronate sulfatase gene alterations in 70 unrelated Hunter patients.

Clin Genet.

1998;53:362-368.

5.

Lonergan CL, Payne AR, Wilson WG, et al. What syndrome is this? Hunter syndrome.

Pediatr Dermatol.

2004;21:679-681.

6.

Thomas GH. Disorders of glycoprotein degradation: a-mannosidosis, b-mannisidosis, fucosidosis, and sialidosis. In:

The Metabolic & Molecular Bases of Inherited Disease.

8th ed. New York: McGraw-Hill; 2001:3507-3533.