Recent Advances in the Diagnosis and Treatment of Niemann-Pick Disease Type C in Children: A Guide to Early Diagnosis for the General Pediatrician

Table 2

Scoring of manifestations, the combination of symptoms, and the patient’s family history, to provide the total NP-C Risk Predication Score (RPS) [4, 9].

Very strong symptoms (40 points per item)	Strong symptoms (20 points per item)	Moderate symptoms (10 points per item)	Weak symptoms (5 points per item)	Ancillary symptoms (1 point per item)
Vertical supranuclear gaze palsy (VSGP) [N]	Isolated splenomegaly with or without hepatomegaly [V]	Ataxia clumsiness or frequent falls [N]	Acquired and progressive spasticity [N]	(i) Hydrops fetalis [V]; (ii) Sibling with fetal ascites [V]
Gelastic cataplexy [N]	Prolonged neonatal cholestatic jaundice [V]	Dysarthria and/or dysphagia [N]	Treatment-resistant psychiatric symptoms [P]	Delayed developmental milestones [N]
	Cognitive decline [P]	Dystonia [N]	Other psychiatric disorders [P]	Seizures [N]
		Psychotic symptoms [P]		Disruptive or aggressive behavior in adolescence and childhood [P]
				(i) Hypotonia [N]; (ii) Myoclonus [N]

(i) N: neurological domain symptoms, V: visceral domain symptoms, and P: psychiatric domain symptoms.
(ii) Combined manifestations (scores): V + N = 40 points, V + P = 40 points, and P + N = 20 points.
(iii) Family history (scores): 1st degree = 40 points and 2nd degree = 10 points.
(iv) Total Risk Predication Score for NP-C: <40 = low probability of NP-C and alternative causes should be considered. A score of 40–69 = moderate suspicion of having NP-C; further follow-up observation is required and contact NP-C referral center for further discussion. A score of ≥70 = high suspicion of having NP-C and should be immediately referred to an NP-C center for testing for NP-C.