The first patient, the elder of two children, was a girl born at term. Weight, height, and head circumference measurements were normal and no abnormal features were reported at birth.
We first saw her at the age of 5 years old. She had been referred by an ophthalmologist for specialized ophthalmic examination after low visual acuity and macular cherry-red spots were identified during a routine examination. In her medical history, we noted a nystagmus diagnosed 2 years earlier and not yet investigated, and ear tubes (myringotomy) for chronic otitis media. No other particular clinical events were reported.
The ophthalmic examination showed best-corrected visual acuity at 20/63 in the right eye and 20/80 in the left eye, with mild myopia. We observed a vertical downbeat nystagmus that increased on downward gaze and decreased on upward gaze. During the upward gaze, the head was bent forward in a torticollis-like position. In both eyes, peripheral evaluation of the visual field, slit-lamp examination, and visual evoked potentials were normal. The dilated fundus examination unveiled typical bilateral macular cherry-red spots (Figure 1
). The peripheral retina and optic nerve heads were normal. SD-OCT (Cirrus; Carl Zeiss Meditec, Inc., Dublin, CA) revealed increased reflectivity from the inner retinal layer (Figure 2
). These clinical findings were suggestive of a lysosomal storage disease. The child was then referred to the pediatric department for further examinations.
Figure 1. Right eye fundus examination of case 1 showing a cherry-red spot.
Figure 2. Right eye spectral-domain optical coherence tomography of case 1 showing increased reflectivity of the inner retinal layers.
Pediatric examination showed normal weight (0 standard deviation [SD]), height (−1 SD), and head circumference (+1 SD), and coarse facial features. Neurological examination revealed a slight hypotonia. Orthopedic examination showed bilateral genu valgum and flat feet with a valgus deformity. There was no psychomotor delay but we noted slightly impaired executive functions. The abdominal sonogram revealed a hepatosplenomegaly. Full blood count showed 8% of vacuolated lymphocytes.
Myelography showed numerous large histiocytes with cytoplasm filled with unstained vacuoles. Urinalysis showed a high rate of sialylated oligosaccharides, suggesting glycoproteinosis. Enzymatic studies on cultured skin fibroblasts revealed normal β-galactosidase activity and low α-D-neuraminidase activity, confirming the diagnosis of sialidosis.
Results from other investigations, including brain magnetic resonance imaging (MRI), cardiac ultrasound, respiratory function (with lung x-rays, pulmonary function tests, and measurements of nocturnal oxygen saturation), and skeletal x-rays were normal. These clinical and biological findings were compatible with a diagnosis of type II infantile-onset sialidosis.
The child has been observed every 3 months for pediatric clinical examination and annual complete inpatient clinical and imaging review.
At the age of 6 years, the child developed a sleeping disorder associated with anxiety that was treated with amitriptyline. Mild changes to the white matter were observed on the MRI and have remained stable since. At the age of 7 years old, she exhibited joint stiffness and a scoliosis-like posture, which were treated by physiotherapy. Lung examination revealed mild obstructive pulmonary disease not requiring treatment. At the age of 8 years, a skeletal survey showed disc degeneration at T12-L1, which has remained stable. At the age of 9 years, we noted mild conductive hearing loss on the left side due to otosclerosis and bone fusion.
At the 5-year follow-up there was no psychomotor delay and weight had regularly increased (+2 SD) but height was below −2 SD. Ophthalmic examination showed improvement in visual acuity (20/25 in the right eye and 20/32 in the left eye at the last follow-up examination), but the nystagmus remained. The dilated fundus and SD-OCT examination results remained identical to those of the initial examination, with the typical macular spot and increased reflectivity from the inner retinal layer. At the last follow-up examination, visual field testing showed decreased global sensitivity with a paracentral scotoma on the right eye and a central scotoma on the left eye.
After discovering the typical macular cherry-red spot in our index patient, we conducted an ophthalmic examination of her 3-year-old sister, who had an uneventful medical history apart from chronic serous otitis media.
Her visual acuity was 20/80 in the right eye and 20/63 in the left eye with mild myopia. We noted no abnormal eye movements. Peripheral evaluation of the visual field, slit-lamp examination, and visual evoked potentials were normal. The dilated fundus examination showed bilateral macular cherry-red spots. The peripheral retina and optic nerve heads were normal. The SD-OCT examination unveiled the same findings as in case 1.
Pediatric examination reported the same clinical features as in case 1 except for excessive weight.
Case 2 was also been classified as type II infantile-onset sialidosis. The 3-year-old girl had the same medical follow-up as her sister.
During the 5-year follow-up examination, vertical downbeat nystagmus, multiple ear, nose, and throat infections that required tonsillectomy and adenoidectomy, severe perceptive and conductive hearing loss, mild changes to the white matter on brain MRI, sleeping disorder, anarchic vertebral body ossification, cerebellar syndrome with walking instability, and mild psychomotor delay were reported.
Ophthalmic examination showed an improved visual acuity (20/32 in the right eye and 20/32 in the left eye with mild myopia at the last follow-up examination), and results of dilated fundus and SD-OCT examinations remained the same. At the last follow-up examination, visual field testing showed decreased global sensitivity with bilateral central scotoma and impaired upper peripheral visual field.