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.