Biochemical study: increased plasma oxysterols
Molecular test: homozygous NPC2 gene variant
Diagnosis: Niemann-Pick disease type C
Niemann-Pick disease type C (NPC) is an autosome recessive lipid storage disease caused by mutations in NPC1 or NPC2 genes which result in a defect in cellular cholesterol trafficking leading to the accumulation of unesterified cholesterol in late endosomes/lysosomes. Age of onset is variable and ranges from perinatal period to adulthood, and clinical presentation is also highly variable. Most individuals are diagnosed during childhood with symptoms including ataxia, vertical supranuclear gaze palsy, dystonia, progressive speech deterioration, and seizures resulting in death by the second or third decade of life. Adult-onset NPC is associated with a slower progression and is characterized by psychiatric illness, ataxia, dystonia, and speech difficulties. Current therapeutic approaches focus on multidisciplinary symptom control and deceleration of disease progression. Miglustat is the drug approved in many countries for treating progressive neurological complications of NPC.
The diagnosed is based on characteristic symptoms obtained from a thorough clinical evaluation, and confirmed by a variety of specialized tests. Traditionally staining the patient’s fibroblasts for level of unesterified cholesterol accumulation (filipin staining) was considered gold standard for NYC diagnosis. Recently, blood-based biomarkers (oxysterols, lysosphingolipids, and bile acid metabolites) and gene sequencing of NPC1 and NPC2 have become diagnostic tests and shown good sensitivity and specificity.
Molecular test: homozygous NPC2 gene variant
Diagnosis: Niemann-Pick disease type C
Niemann-Pick disease type C (NPC) is an autosome recessive lipid storage disease caused by mutations in NPC1 or NPC2 genes which result in a defect in cellular cholesterol trafficking leading to the accumulation of unesterified cholesterol in late endosomes/lysosomes. Age of onset is variable and ranges from perinatal period to adulthood, and clinical presentation is also highly variable. Most individuals are diagnosed during childhood with symptoms including ataxia, vertical supranuclear gaze palsy, dystonia, progressive speech deterioration, and seizures resulting in death by the second or third decade of life. Adult-onset NPC is associated with a slower progression and is characterized by psychiatric illness, ataxia, dystonia, and speech difficulties. Current therapeutic approaches focus on multidisciplinary symptom control and deceleration of disease progression. Miglustat is the drug approved in many countries for treating progressive neurological complications of NPC.
The diagnosed is based on characteristic symptoms obtained from a thorough clinical evaluation, and confirmed by a variety of specialized tests. Traditionally staining the patient’s fibroblasts for level of unesterified cholesterol accumulation (filipin staining) was considered gold standard for NYC diagnosis. Recently, blood-based biomarkers (oxysterols, lysosphingolipids, and bile acid metabolites) and gene sequencing of NPC1 and NPC2 have become diagnostic tests and shown good sensitivity and specificity.
Apostolos Papandreou and Paul Gissen. Diagnostic workup and management of patients with suspected Niemann-Pick type C disease. Ther Adv Neurol Disord. 2016 May; 9(3): 216–229.