Walterfang, Mark

ABSTRACT In 2018, the International Niemann‐Pick Disease Alliance (INPDA) and the International Niemann‐Pick Disease Registry (INPDR) developed and published comprehensive clinical management guidelines to support inclusive and standardized care pathways in Niemann‐Pick disease type C (NPC)—an ultra‐rare, autosomal recessive, neurovisceral lysosomal disorder. Since then, advances in diagnostics, care, and the approval of two novel disease‐modifying agents have underscored the need to revise these guidelines to ensure safe, consistent, and high‐quality care for those affected by NPC. In response, the INPDA and INPDR convened a multidisciplinary Guidelines Development Group (GDG) comprising individuals with NPC expertise from 14 countries across five continents, representing a broad range of specialties, as well as patients and families involved in NPC care. Informed by a comprehensive literature review and two meetings, the GDG systematically reviewed, revised, and updated the 2018 guideline statements, re‐evaluating the level of evidence, strength of recommendations, and expert agreement for each. The resulting 2025 consensus clinical management guidelines constitute a timely, up‐to‐date, and internationally applicable resource for the diagnosis, treatment, and holistic management of individuals with NPC. These guidelines serve as a critical resource for specialist centers, hospital‐based medical teams, staff involved in NPC patient care, family physicians and other primary caregivers, and, importantly, patients and their families.

AbstractObjectiveThe Suspicion Index (SI) screening tool was developed to identify patients suspected of having Niemann‐Pick disease type C (NP‐C). The SI provides a risk prediction score (RPS) based on NP‐C manifestations within and across domains (visceral, neurological, and psychiatric). The aim of these subanalyses was to further examine the discriminatory power of the SI by age and manifestation–associations by NP‐C suspicion‐level and leading manifestations.MethodsThe original retrospectively collected data were split into three patient age groups, where NP‐C‐positive cases were >16 years (n = 30), 4–16 years (n = 18), and <4 years (n = 23), and patients’ RPS were analyzed by logistic regression. Co‐occurrence of manifestations within groups of suspicion level (low, medium, high) and leading manifestations (presence/absence of ataxia, cognitive decline, psychosis, and splenomegaly) were analyzed descriptively.ResultsNP‐C‐positive cases versus controls showed strong discriminatory power of RPS. Area under the receiver operating characteristic curve was 0.964 (>16 years) and 0.981 (4–16 years) but weaker 0.562 for infants (<4 years). Patients with RPS <70 were characterized by a lack of psychiatric manifestations and low levels of neurological involvement, suggestive of a preneurological phase of the disease. In patients >4 years, prominent leading manifestation–associations were ataxia with dystonia, dysarthria/dysphagia, and cognitive decline. Psychosis was associated with dysarthria/dysphagia but also with cognitive decline and treatment‐resistant psychiatric symptoms.ConclusionsThe SI tool maintains strong discriminatory power in patients >4 years but is not as useful for infants <4 years. The SI is also informative regarding the association and co‐occurrence of manifestations in patients with NP‐C.