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Early diagnosis of Niemann-Pick disease type C (NP-C) in neonatal cholestasis is still challenging because splenomegaly is non-specific and oxysterol profiling studies also have a relatively low specificity. This study explores a method for identifying infants with a high clinical suspicion of NP-C in neonatal cholestasis. We reviewed the clinical findings of 9 neonatal cholestatic infants with NP-C genetically diagnosed between January 2015 and December 2020. Seven underwent liver biopsy at ages ranging from 35 to 112 d. Foam cells were only detected in 2 (28.6%, 2/7) liver tissues obtained beyond 3 months of age. However, vacuolated Kupffer cells were detected in all 7 liver tissues. Their significance was explored by using 168 neonatal cholestatic infants, who underwent genetic tests and liver biopsy between January 2018 and December 2020. Of them, 26 detected vacuolated Kupffer cells. Six (23.1%, 6/26) were diagnosed as NP-C, comparing to none of the 142 neonatal cholestatic infants without vacuolated Kupffer cells (χ2 = 33.983, p < 0.001). The ratio of positive diagnosis of NP-C was 31.6% (6/19) in neonatal cholestatic infants with both vacuolated Kupffer cells and splenomegaly. Therefore, we conclude that the presence of vacuolated Kupffer cells can raise a high clinical suspicion of NP-C in neonatal cholestatic infants, especially in those with splenomegaly.

Additional file 1. Renal images in additional patients.

Additional file 2. Table S1. Pathogenicity prediction of novel variants in HSD3B7; Table S2. Previously reported variants in HSD3B7; Table S3. Serum liver biochemistries at first referral and at last follow-up; Table S4. Correlation of genotype and phenotype in patients with HSD3B7 deficiency.

Mutation analysis of the GPD1 gene in the proband and her parents. The patient was a homozygote and her parents were heterozygous for the mutation. (DOCX 853 kb)

Reported genes associated with acute liver failure. (DOCX 16 kb)

Details of RALF in patient 3. ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyl transpeptidase; INR, international normalized ratio; TB, total bilirubin; TBA, total bile acids. (DOCX 15 kb)

Variant filtering strategy for patients 1â 5. A. Filtering procedure for suspected pathogenic genes for a single sample. B. Filtering procedure for candidate gene list. ALF, acute liver failure. (DOCX 81 kb)

Sequencing statistics for patients 1â 5. (DOCX 14 kb)

Ages during episodes of ALF and liver crises. P, patient. ALF, acute liver failure. N1, episodes of ALF. N2, episodes of acute liver crisis. The age of last following up for patients 1â 3 is 6y 11Â m, 4y 8Â m, and 2y4m, respectively. With the increasing age, the episodes of ALF and RALF were not decreased (DOCX 14 kb)

Candidate genes for patients 1â 5. (DOCX 14 kb)

Specific primers for NBAS exons 8, 22, 31, 43, and 50. (DOCX 14 kb)

Two tetrapus molecules,1a and 1b, were synthesized. They each possess fluorinated tentacles with anionic termini, i.e., CH2O(CH2)3(CF2)2O(CF2)2SO3−,Na+ for 1a and CH2O(CH2)3(CF2)4O(CF2)2SO3−,Na+ for 1b. Cationic and anionic naphthalene fluorescence probes with CH2CH2O(CH2)10-chains (Fp+ and FP−) were used to study host-guest interactions between partners of the following pairs, i.e., 1a and FP+, 1a and FP−, 1b and FP+, 1b and FP−. Our results demonstrate that electrostatic attraction is a powerful factor in facilitating the host-guest interactions between the tetrapus and the long-chain probes.

The effects of magnetic saturation on the steady-state synchronous reactance have been fully studied. By using the 2D P.E.M., the steady-state saturated reactances are determined directly from flux linkages. The variation of direct synchronous reactance Xd with saturation under zero-power-factor (lag or lead) condition, purely quadrature magnetising, and rated load condition are presented. Also the saturated values of quadrature synchronous reactances Xq under these conditions, as well as the coupling reactances Xdq end Xqd between d- and q- axes are presented.