Diagnosis

Find a Diagnostic Centre:

Looking for a diagnostic centre in your country?  Visit Orphanet! Orphanet is a unique resource, aiming to provide high-quality information on rare diseases, and ensure equal access to knowledge for all stakeholders.

Recognising the Signs and Symptoms of NP-C:

Think NP-C. Talk NP-C – Ataxia

Think NP-C. Talk NP-C – Dysarthria

Think NP-C. Talk NP-C – Gelastic Cataplexy

Think NP-C. Talk NP-C – Hepatosplenomegaly

Think NP-C. Talk NP-C – Organic Psychosis

Think NP-C. Talk NP-C – Vertical Supranuclear Gaze Palsy

Think Again. Think NP-C Educational Slide Deck

The NPC Suspicion Index:

Niemann–Pick disease type C (NPC) is a rare, progressive neurovisceral disorder caused by pathogenic variants in NPC 1 or NPC 2.  It presents across the life span with varied combinations of visceral,neurological,and psychiatricfeatures.  Although prevalence is commonly cited as 2–3 per million, true rates are likely higher due to under-recognition of mild or atypical phenotypes.

Early manifestations of NPC are often non-specific, leading to frequent misdiagnosis and diagnostic delay, which limits opportunities for timely disease-modifying treatment and targeted supportive care.

To address this gap, an international working group of clinicians,  scientists, and patient-organization leaders has re-established the NPC Suspicion Index (NPC-SI), first  introduced over a decade ago, to reflect current evidence and practice.  The NPC-SI is a simple, interactive screening tool to support healthcare professionals in the early identification and referral of individuals suspected of NPC.

Two age-specific versions of the NPC-SI are available at NPC-SI.org, The website provides interactive calculators, downloadable resources, and educational tools that reflect advances in epidemiology, genotype–phenotype understanding, and clinical presentation across the lifespan. For both NPC-SI tools, a risk prediction score (RPS) is calculated based on the presentation of key clinical symptoms of NPC and the individual’s family history, indicating the level of suspicion for NPC.

ASMD Perspective Index

Acid Sphingomyelinase Deficiency (ASMD) Perspective Index

Acid Sphingomyelinase Deficiency (ASMD) is a rare genetic disorder resulting from mutations in the SMPD1 gene, which causes deficient activity of the acid sphingomyelinase enzyme. This deficiency leads to sphingomyelin accumulation in various tissues, triggering a wide range of symptoms affecting multiple organ systems. ASMD spans a clinical spectrum from severe infantile neurovisceral disease to more chronic visceral or neurovisceral forms that can present from childhood through adulthood. Early manifestations are often non-specific, contributing to frequent diagnostic delay and missed opportunities for timely intervention.

The ASMD Perspective Index is a digital awareness tool developed by Niemann-Pick UK (NPUK), in collaboration with the International Niemann-Pick Disease Alliance (INPDA) and wider partners. It is designed to assist healthcare providers in recognising potential ASMD cases by guiding them through an online survey of key clinical signs and symptoms (including hepatosplenomegaly, valvular abnormalities, ataxia, and other relevant visceral, pulmonary, haematological, and neurological features).

By highlighting patterns that may indicate ASMD, the Index aims to increase awareness among clinicians, support earlier suspicion of the condition, and encourage timely diagnostic testing (enzyme assay and/or genetic analysis) together with specialist referrals for confirmation and management.

The ASMD Perspective Index is available at: https://www.npuk.org/asmdindex/

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