Novel CLN1 mutation with atypical juvenile neuronal ceroid lipofuscinosis
An 11-year 10-month-old Caucasian boy with normal perinatal and neuro-developmental history was referred to us with a 3 year history of progressive visual loss and visual hallucinations. His symptoms started with difficulty in reading, worsening handwriting and flashes of lights in both eyes. He gave us a description and consistently drew figures [], which he appeared to be seeing in front of his eyes. The figures had a red border with circles and lines criss-crossing the circles.\nOver the past 12 months, he had been investigated extensively and no cause had been identified. The visual acuity (VA) at first presentation was 6/60 in both eyes, when he was 10 years and 11 months old. VA improved to 6/36 in both eyes after 1 month. Interestingly, 6 months later, his left eye deteriorated to 6/60, but right eye had normal visual acuity (6/6). Ophthalmologist was pleased and found that he had enrolled in an archery course for the summer and was doing fairly well. However, 4 months later, VA deteriorated to 6/60 in both eyes. At the last follow-up, at 12 years and 4 months of age, VA was 6/60 in the right eye and 3/60 in the left eye. He was able to detect colors on the Ishihara chart but could not read any letters. His visual field test did not show specific defect. Pupillary reaction was normal with no relative afferent pupillary defect. Fundoscopic examination still showed healthy optic disc and healthy macula at the last ophthalmology follow-up. Neurological and other examinations were unremarkable.\nVEP of both eyes were delayed while ERG was normal at 12 years. Cranial/orbit magnetic resonance imaging (MRI) and electroencephalography (EEG) were normal. Test for Leber′s hereditary optic neuropathy was normal. Skin and muscle biopsy did not demonstrate any inclusion bodies. Blood film showed no lymphocyte vacuolation. However, electron microscopy of buffy coat showed rare, membrane bound, electron dense, granular material associated with a lipid droplet in the cytoplasm of lymphocytes. Leukocyte enzyme analysis showed very low level of Palmitoyl protein transferase (PPT) activity measuring 2.2 nmol/hr/mg ptn (Normal = 17–139) and normal Tripeptidyl peptidase I (TPP-I) 214 nmol/hr/mg ptn (Normal: 42–339). Molecular genetic analysis of exon 1 to 9 of CLN1 gene showed that he was heterozygote for p.Cys96Tyr and p.Arg151X mutations.\nA diagnosis of milder form of INCL (CLN1) was made. At his last neurology follow-up at 12 years and 10 months, his vision remained poor. He had developed behavior and cognitive problems. His behavior was becoming increasingly immature. There had been loss of skills and significant change in his memory. He had never had any seizures and motor dysfunction to date.