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Sialidosis (Mucolipidosis I) Clinical Presentation

  • Author: Karl S Roth, MD; Chief Editor: Luis O Rohena, MD  more...
 
Updated: Nov 03, 2015
 

History

In general, sialidosis is a heterogenous disorder with a wide spectrum of variability in disease manifestation.

Patients with the type II infantile form may be normal or almost normal in appearance at birth. Coarse facial features, developmental delay, and hepatosplenomegaly may develop within the first year of life.

Although not as severe as the Hurler phenotype, similar-appearing coarse features, hepatosplenomegaly, and skeletal abnormalities (dysostosis multiplex) become more pronounced with time. Short stature may also progressively develop.

The extent of neurologic progression varies, but macrocephaly, hypotonia, nystagmus, visual impairment, and myoclonic seizures are known to develop. Cherry-red spots appear with age in most patients. As the neurologic picture progresses, these patients become nonambulatory and are unable to care for themselves.

In the congenital form, hepatosplenomegaly, ascites, and hydrops fetalis are noted at birth, and the infant may be stillborn. In those who survive postnatally, the course is rapidly progressive.

Nephrosis has been reported in some patients; these patients may comprise a subgroup of the infantile form.

Patients with the adult form of the disease first report visual impairment due to color blindness or night blindness. Cherry-red spots are present in virtually all such patients. Myoclonus, which can be disabling, and ataxia develop later.

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Physical

Neurologic findings include the following:

  • Developmental delay or mental retardation
  • Visual impairment or loss of visual acuity
  • Hypotonia
  • Myoclonus
  • Nystagmus, ataxia, and seizures (have been reported)

Coarse facial features include the following:

  • High forehead, puffy eyelids, epicanthal folds
  • Flat nasal bridge, anteverted nares, long philtrum
  • Gingival hypertrophy, macroglossia

Skeletal abnormalities include the following:

  • Lumbar gibbus deformity and kyphoscoliosis
  • Joint stiffness and contractures (may develop)

Ophthalmologic findings include cherry-red macula, corneal opacities, lens opacities, and lamellar cataracts. Abdominal findings include hepatosplenomegaly in patients with the type II form as a result of visceral storage. Findings in the congenital form include hydrops fetalis, neonatal ascites, hepatosplenomegaly, and inguinal hernia.

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Causes

Sialidosis is an autosomal recessive disorder caused by an isolated deficiency of the enzyme, alpha-N -acetyl neuraminidase (also called sialidase). Three distinct human neuraminidases are known and are specifically localized to the cytosol, plasma membrane, and lysosome. The lysosomal enzyme is selectively deficient in human sialidosis. The lysosomal neuraminidase gene maps to chromosome 6p21 and has been cloned. Various enzyme-inactivating mutations have been identified in patients with sialidosis.

The variability of disease manifestation due to this enzyme deficiency, as evidenced by the 3 disease subtypes, has indicated a potential genotype-phenotype correlation. Research has shown that the type of gene mutation affects not only enzyme activity but also whether the enzyme localizes to the lysosome. Preliminary studies indicate that both of these properties have positively correlated with the clinical subtype of sialidosis.[3] However, the wide variability of clinical presentation in these patients cannot be fully explained by alpha-N -acetyl neuraminidase mutations. Therefore, other environmental or genetic factors probably account for the varying degrees of disease severity.

More than 40 mutations in the NEU1 gene have been described. Most are missense mutations, but deletions and insertions have also been described. In multiple small studies, sequencing identified all mutations in the NEU1 gene.[4, 5, 6]

 

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Contributor Information and Disclosures
Author

Karl S Roth, MD Retired Professor and Chair, Department of Pediatrics, Creighton University School of Medicine

Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, Society for Pediatric Research, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Coauthor(s)

Margaret M McGovern, MD, PhD Professor and Chair of Pediatrics, Stony Brook University School of Medicine

Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics

Disclosure: Nothing to disclose.

William B Rizzo, MD Professor, Department of Pediatrics, University of Nebraska Medical Center

William B Rizzo, MD is a member of the following medical societies: American Society of Human Genetics, Society for Inherited Metabolic Disorders

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Margaret M McGovern, MD, PhD Professor and Chair of Pediatrics, Stony Brook University School of Medicine

Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

Edward Kaye, MD Vice President of Clinical Research, Genzyme Corporation

Edward Kaye, MD is a member of the following medical societies: American Academy of Neurology, Society for Inherited Metabolic Disorders, American Society of Gene and Cell Therapy, American Society of Human Genetics, Child Neurology Society

Disclosure: Received salary from Genzyme Corporation for management position.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Grace Y Lee, MD, to the development and writing of this article.

References
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