Pitfalls in Diagnosing Neuraminidase Deficiency: Psychosomatics and Normal Sialic Acid Excretion

  • Imre F. Schene
  • Viera Kalinina Ayuso
  • Monique de Sain-van der Velden
  • Koen L. I. van Gassen
  • Inge Cuppen
  • Peter M. van Hasselt
  • Gepke VisserEmail author
Case Report
Part of the JIMD Reports book series (JIMD, volume 25)


Neuraminidase deficiency (mucolipidosis I, sialidosis types I and II, cherry-red spot myoclonus syndrome) is a lysosomal storage disorder with an expanding clinical phenotype. Here, we report the striking diagnostic history of late-onset neuraminidase deficiency in two sisters, currently aged 14 (patient 1) and 15 (patient 2).

Patient 1 was referred for evaluation of her vision after a traffic accident. During this examination, nummular cataract, macular cherry-red spot, and optic nerve atrophy were seen. Furthermore, tremors were noticed in her arms and legs. This combination suggested a lysosomal storage disorder. Her family history revealed an older sister, patient 2, who had a long history of unexplained neurologic symptoms; she was under unsuccessful treatment for conversion disorder. Patient 2 showed identical ophthalmological findings. In retrospect, she had presented with avascular osteonecrosis of the right femur head at age 9.

Urinary oligosaccharide patterns and enzyme activity revealed neuraminidase deficiency in both patients. Urinary-bound sialic acid levels were normal. Sequencing of NEU1 demonstrated two known compound heterozygous mutations (c.1195_1200dup p.His399_Tyr400dup; c.679G>A, p.Glu227Arg).

The substantial time window between onset of typical symptoms and diagnosis in patient 2 suggests inadequate awareness of lysosomal storage disorders among clinicians. Of special interest is the observation that normal urinary sialic acid levels do not exclude neuraminidase deficiency. Urinary oligosaccharide screening is essential to diagnosis in such cases. In addition, patient 2 is the fourth case in the literature with a history of femur head necrosis. Bone defects might therefore be an early manifestation of late-onset neuraminidase deficiency.


Fabry Disease Conversion Disorder Lysosomal Storage Disorder Compound Heterozygous Mutation Downbeat Nystagmus 
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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Imre F. Schene
    • 1
  • Viera Kalinina Ayuso
    • 2
  • Monique de Sain-van der Velden
    • 3
  • Koen L. I. van Gassen
    • 4
  • Inge Cuppen
    • 5
  • Peter M. van Hasselt
    • 1
  • Gepke Visser
    • 1
    Email author
  1. 1.Department of Metabolic Diseases, Wilhelmina Children’s HospitalUniversity Medical Centre UtrechtUtrechtThe Netherlands
  2. 2.Department of OphthalmologyUniversity Medical Centre UtrechtUtrechtThe Netherlands
  3. 3.Department of Medical Genetics, Wilhelmina Children’s HospitalUniversity Medical Centre UtrechtUtrechtThe Netherlands
  4. 4.Department of Medical GeneticsUniversity Medical Centre UtrechtUtrechtThe Netherlands
  5. 5.Department of Neurology, Wilhelmina Children’s HospitalUniversity Medical Centre UtrechtUtrechtThe Netherlands

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