the natural history of sialidosis type i

Conditions: Observational Study

Summary: sialidosis type 1 is an autosomal recessive disorder caused by bialleic neu1 gene mutations. patients with sialidosis type i present variable neurological and eye dysfunction and the progression rate is variable. the goal of this protocol is to assess the neurological and ophthalmological status of these patients and characterize the clinical and laboratory abnormalities in order to determine the natural history of the disease. patients will be followed every 6 month with comprehensive clinical, neurological and ophthalmological examinations combined with neuropsychological, blood, radiological and electrophysiological tests.

sialidosis is a rare autosomal recessive genetic disorder caused by a deficiency of sialidase with an estimated prevalence rate of one patient per 250,000 people. sialidase, also known as neuraminidase i or neu1, is an enzyme found inside lysosomes. patients with sialidosis lack neu1 due to genetic mutations, leading to low levels or impaired function of sialidase in cells. as a result, sialic acid cannot be effectively removed from glycoproteins or glycolipids, causing abnormal accumulation of these substances in cells, which can lead to cellular dysfunction or even death. sialidosis is divided into two types: type ii patients show severe symptoms in infancy, while type i patients develop symptoms from childhood to adolescence, followed by a slow, progressive deterioration. typical symptoms of type i sialidosis begin with unsteady gait and may include progressive visual impairment, muscle twitches (myoclonus), muscle weakness and atrophy, coordination difficulties, seizures, and mild intellectual disability. as muscle tremors worsen, activities like sitting, standing, and walking become challenging. progressive vision loss can cause color blindness or night blindness, and cherry-red spot abnormalities may appear on eye exams. the progressive nature of the sialidosis type is variable. some patients have clear deterioration, while others seem to stay at the same level of the disease for a long time. this study aims to track the natural history of patients with sialidosis type i to identify suitable clinical markers for measuring disease progression speed. it is an observational study involving non-invasive routine examinations without treatment, thus posing no additional risk to patients. patients with a definite diagnosis of this disease are candidates for this study. patients will receive physical and neurological examination every 6 month with a total duration of 24 months. a history will be taken and a physical exam done. blood and urine tests will be done along with brain wave recording, complete eye examination, cognitive test, gait analysis, and myoclonus evaluation. a maximum of 10ml of blood will be drawn from recruited patient. various eye tests will also be done. dna will be extracted and the plasma will be retained for possible use in the future studies. brain mri without contrast, evoked potentials of visual and somatosensory systems, nerve conduction study and nerve excitability test will be done annually. medication record and the response to treatment will be recorded as well. there is a possibility of improved medical management and rehabilitative treatment as a result of participating in this study.

Eligibility criteria:
inclusion criteria: * subjects must: * genetic diagnosis of sialidosis type i * able to tolerate a general exam and neurological exam * able to tolerate a modest amount of blood drawing * able to tolerate the complete electrophysiological studies * able to tolerate the performance of electroencephalogram and brain mri * able to tolerate a neuropsychological testing and opathalmology evaluation exclusion criteria: * patients who cannot tolerate the scheduled examinations and blood drawing

Keywords: sialidosis neu1 gene natural history