New Npc Suspicion Index



Ashrfi MR¹ ; Tavasoli A¹ Show Affiliations
Source: Genetics in the Third Millennium Published:2016

Abstract

NP-C is a severe, progressive and irreversible neurovisceral disease, which is invariably fatal. NP-C is a rare disease, with an estimated minimal incidence of 1/120,000 live births. NP-C is caused by mutations in NPC1 (~95% of patients) or NPC2 genes. Defective NPC1 and NPC2 proteins result in a disruption of lipid metabolism. One of special features of this disorder is heterogeneous manifestations. Overall various clinical manifestation of NPC disease can be categorized in three main groups: Visceral or systemic, neurological and psychiatric. The most important clinical features of each group are as follow: Visceral (prolonged neonatal jaundice, unexplained splenomegaly with or without hepatomegaly), neurological (vertical supranuclear gaze palsy, gelastic cataplexy), Psychiatric (early cognitive decline or dementia).In addition of variable clinical features, NPC disease has a wide range of age manifestation, from neonatal period through adulthood. Neurologic features unlike visceral symptoms are not common under early infancy period. After that neurological symptoms become prominent and finally from juvenile period through adolescent/adult age psychiatric symptoms in addition of neurological signs will present.Therefore with considering the variability in clinical presentations and age manifestation of NPC disease, it seems a little hard to diagnose the disease. The NP-C Guidelines Working Group revised the recommendations for the diagnosis and management of Niemann-Pick type C disease in 2012, to provide the most up-to-date information about NP-C. A new tool – the NP-C Suspicion Index – has also been developed for healthcare professionals to help identify patients for whom further investigation is required. This will hopefully help to achieve earlier and improved diagnosis of NP-C in patients suspected of having the disease. Suspicion index is one of important tools for early diagnosis of NPC disease that developed in 2012 by Wijburg et al. Early diagnosis is important, because it help us to start early treatment with Zavesca (the only available drug for NPC disease that acts as a substrate reduction therapy). This process finally helps to patients with reducing the progression of disease. From a physician’s point of view the Suspicion Index works both as a reminder of the complex and varied symptoms characteristic of NP-C, as well as support in making the right referral decision.Suspicion index likes a checklist and fill it tells us the NPC risk prediction score. The three main categories of disease symptoms have been ranked into five groups according it’s importance. Co-Occurrence of symptoms (within and across categories) and family history are also taken into account to define the Risk Prediction Score. NPC SI Interpretation: 1.A total Risk Prediction Score of ≥70 indicates a high suspicion of having NP-C and should lead to immediate referral of the patient to a NP-C center for testing about NP-C according to local practice. 2.A total Risk Prediction Score of 40–69 indicates a Moderate suspicion of having NP-C, and should lead to further follow-up, including discussion with a NP-C center. 3. A total Risk Prediction Score of <40 indicates a low probability of having NP-C, and alternative causes should be considered before further investigation for NP-C. Analysis of SI discriminatory ability by age groups showed a high performance in study patients aged >4 years, but the discriminatory performance was low for patients aged ≤4 years. Due to a lower sensitivity in patients below 4 years old, a prediction score below 70 is not conclusive in this group of patients. The infantile NP-C SI 0–4y is designed for patients aged <4 years. Carefully assess the signs and symptoms, selecting those that are present in your patient .Pay close attention to the co-occurrence of ataxia and/or mental regression with central nervous system or spleen symptoms .Calculate the total risk predication score for your patient by adding the totals for each category . © 2016, Iranian Neurogenetics Society. All rights reserved.