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. 2016;25:9-13.
doi: 10.1007/8904_2015_472. Epub 2015 Jul 5.

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

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

Imre F Schene et al. JIMD Rep. .
Free PMC article

Abstract

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.

Figures

Fig. 1
Fig. 1
(a) Fundoscopy in patients 1 and 2, at the age of 13 and 14, respectively, showed bilateral (only the right eye is shown) cherry-red spot in the macula (arrow) and atrophy of the optic nerve. (b) Slit lamp examination revealed bilateral nummular cataract in both patients
Fig. 2
Fig. 2
X-ray of the pelvis in patient 2 at age 12 showed mild flattening and mild sclerosis of the right femur head as a result of avascular osteonecrosis (Legg–Calvé–Perthes syndrome) that started at age 9. Revascularization occurred spontaneously within 3 years, but pain and unsteadiness of the right hip remained
Fig. 3
Fig. 3
Thin-layer chromatography of urinary oligosaccharides showed patterns compatible with galactosialidosis or neuraminidase deficiency (sialidosis) in both patients (Holmes and O’Brien 1979). The third panel serves as pathologic standard for both disorders. This method cannot distinguish galactosialidosis from neuraminidase deficiency. Enzyme activity testing in cultured fibroblasts is required for diagnosis

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