Child ; Humans ; Male ; Niemann-Pick Disease, Type C ; diagnosis ; genetics

Niemann-Pick disease type C (NPC) is an autosomal recessive lysosomal lipid storage disease associated with impaired intracellular cholesterol trafficking. A wide spectrum of clinical phenotype has been described, with a possible onset at all ages of life from the neonatal period to adulthood, more often in childhood. Typically, hepatosplenomegaly, dystaxia, dysphagia, dysarthria and dementia are presented in NPC patients. Neurologic symptoms vary according to the onset age, but prolonged neonatal cholestasis, splenomegaly, cataplexy and vertical supranuclear gaze palsy are more specific signs to the diagnosis of the disease. Impaired cholesterol trafficking and unesterified cholesterol accumulation in the late endosomes and lysosomals, as a results of mutations in NPC1 or NPC2 genes, are initial for the disease, and defective cellular autophagy, defective lysosomal calcium homeostasis and oxidative stress may all play roles in the physiological processes. The definite diagnosis requires demonstration of unesterified cholesterol accumulated in fibroblasts cultured from skin biopsies or of pathogenic mutation of NPC1/NPC2 genes. Miglustat, the only available treatment approved to date, can alleviate neurological symptoms and slow disease progression when administered earlier.
Diagnosis, Differential ; Humans ; Niemann-Pick Disease, Type C ; diagnosis ; etiology ; genetics ; therapy

To study the pathological mechanisms of Niemann-Pick disease type C1, we observed the changes of activation of glial cells in the olfactory bulb of Npc1 mutant (Npc1(-/-)) mice. The genomic DNA was extracted from mouse tails for genotyping by PCR. Immunofluorescent histochemistry was performed to examine the activation of microglia and astrocytes in the olfactory bulb of Npc1(-/-) mice on postnatal day 30. NeuN, phosphorylated neurofilament (NF), Doublecortin (DCX), CD68 and GFAP were detected by Western blot. The results showed that Npc1 gene mutation strongly increased the activation of astrocytes and microglia in olfactory bulb associated with increased protein levels of CD68 and GFAP. Furthermore, the expression of phosphorylated NF was also significantly increased in the olfactory bulb of Npc1(-/-) mice compared with that in Npc1(+/+) mice. However, DCX expression was significantly reduced. The above results suggest that there are some early changes in the olfactory bulb of Npc1(-/-) mice.
Animals ; Astrocytes ; Axons ; Genotype ; Mice ; Mice, Knockout ; Microglia ; Neuroglia ; Niemann-Pick Disease, Type C ; Olfactory Bulb ; Phosphorylation

Animals ; Brain ; metabolism ; pathology ; Calcium ; metabolism ; Cholesterol ; metabolism ; Glycosphingolipids ; metabolism ; Humans ; Liver ; pathology ; Neurons ; metabolism ; pathology ; Niemann-Pick Disease, Type C ; diagnosis ; etiology ; metabolism ; pathology ; Sphingosine ; metabolism

OBJECTIVE: To delineate the clinical and genetic features of a Chinese boy suspected for Niemann-Pick disease type C. METHODS: The patient underwent clinical examination and was subjected to next generation sequencing. Suspected mutations were validated by Sanger sequencing. Potential impact of the novel mutation was predicted by SIFT, PolyPhen-2 and MutationTaster software. RESULTS: The child has featured hepatosplenomegaly, increased direct bilirubin, jaundiced skin and liver damage. DNA sequencing showed that he has carried compound heterozygous mutations of NPC1 gene, namely c.2728Gc.269C>G (p.P90R), which were inherited from his mother and father, respectively. The c.2728G>A (p.G910S) mutation was previously reported, while the c.269C>G (p.P90R) was a novel mutation. CONCLUSION The child has suffered from Niemann-Pick disease type C due to mutations of NPC1 gene. Above finding has enriched the spectrum of NPC1 mutations and provided a basis for genetic counseling and prenatal diagnosis.
Asian Continental Ancestry Group ; Bilirubin ; Carrier Proteins ; genetics ; Child ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Membrane Glycoproteins ; genetics ; Mutation ; Niemann-Pick Disease, Type C ; genetics

OBJECTIVETo analyze the clinical characteristics of three Chinese cases of Niemann-Pick disease type C patients with neonatal cholestasis as initial presentation, and enhance awareness of Niemann-Pick disease type C among pediatricians.

METHODThree sporadic cases with confirmed Niemann-Pick disease type C initially presented as neonatal cholestasis were retrospectively reviewed in this study. Their peripheral blood specimens were collected after obtaining informed consent. All exons and the intron-exon boundaries of NPC1 gene were examined by bi-directional sequencing.

RESULTThree patients, 1 female and 2 males, aged from 2 months to 5 years and 10 months, all first complained of jaundice in the neonatal period. Laboratory tests showed total bilirubin and direct bilirubin significantly increased with predominant increase of direct bilirubin. Total bile acid, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were also increased, while high-density lipoprotein cholesterol decreased. All patients were also accompanied by hepatosplenomegaly, with two of them having increased bronchovascular markings in chest X-ray. Two heterozygous changes of NPC1 gene, c.2741G>T +c.3020C>G (p. C914F + p. P1007R), c.2177G>C + c.3734_ 3735delCT (p.R726T + p. P1245RfsX12), and c.2054T>C + c.2128C>T(p.I685T + p.Q710X), were identified in patient 1, 2 and 3, respectively.

CONCLUSIONWe reported three cases suffered from Niemann-Pick disease type C with initial presentation as neonatal cholestasis in the mainland of China. For newborns with prolonged jaundice in the neonatal period, as well as neonatal cholestasis, hepatosplenomegaly, Niemann-Pick type C should be included in consideration of differential diagnosis. Genetic testing can identify causative mutations for diagnosis.

Asian Continental Ancestry Group ; Bile Acids and Salts ; Bilirubin ; Child ; Child, Preschool ; China ; Cholestasis ; etiology ; Exons ; Female ; Humans ; Infant ; Infant, Newborn ; Infant, Newborn, Diseases ; Lipoproteins, HDL ; Male ; Mutation ; Niemann-Pick Disease, Type C ; complications ; diagnosis ; genetics ; pathology ; Niemann-Pick Diseases ; Retrospective Studies ; Splenomegaly

Niemann-Pick disease, type C (NP-C), is caused by NPC1 or NPC2 gene mutations. Progressive neurological, psychiatric, and visceral symptoms are characteristic. Here, we present cases of a brother (Case 1) and sister (Case 2) in their mid-20s with gait disturbance and psychosis. For the Case 1, neurological examination revealed dystonia, ataxia, vertical supranuclear-gaze palsy (VSGP), and global cognitive impairment. Case 2 showed milder, but similar symptoms, with cortical atrophy. Abdominal computed tomography showed hepatosplenomegaly in both cases. NPC1 gene sequencing revealed compound heterozygote for exon 9 (c.1552C>T [R518W]) and exon 18 (c.2780C>T [A927V]). Filipin-staining tests were also positive. When a young patient with ataxia or dystonia shows VSGP, NP-C should be considered.
Abdomen/diagnostic imaging ; Asian Continental Ancestry Group/genetics ; Carrier Proteins/genetics ; DNA Mutational Analysis ; Exons ; Female ; Gait Disorders, Neurologic/etiology ; Humans ; Male ; Membrane Glycoproteins/genetics ; Niemann-Pick Disease, Type C/*diagnosis/genetics ; Psychotic Disorders/etiology ; Republic of Korea ; Siblings ; Tomography, X-Ray Computed ; Young Adult

No abstract available.
Acidosis, Respiratory* ; Alkalosis, Respiratory*

Gitelman syndrome (GS) is a renal tubular disorder of the thiazide-sensitive sodium chloride cotransporter, which is located in the distal tubule of the loop of Henle. We present a rare case of GS complicated by severe hyponatraemia and hypophosphataemia. A 17-year-old boy was admitted to our institution with fever and lethargy. The workup revealed typical features of GS, i.e. hypokalaemia, hypomagnesaemia and metabolic alkalosis. In this report, we discuss the differential diagnoses and rationale for accepting GS as the most likely diagnosis. This case was complicated by severe hyponatraemia (115 mmol/L) and hypophosphataemia (0.32 mmol/L). We concluded that the syndrome of inappropriate secretion of antidiuretic hormones could not be ruled out and that respiratory alkalosis was the most likely aetiology of hypophosphataemia. This case report also generates an interesting discussion on water and electrolyte metabolism.
Adolescent ; Alkalosis, Respiratory ; diagnosis ; Electrolytes ; Fever ; Gitelman Syndrome ; complications ; diagnosis ; Humans ; Hyponatremia ; complications ; diagnosis ; Hypophosphatemia ; complications ; diagnosis ; Lethargy ; Male ; Vasopressins ; secretion

This cross-sectional study involved 339 students aged 12-15 at Sapa and Yen Binh regions. It measured and compared indexes such as vital capacity (VC), forced expiratory volume 1 (FEV1), and Tiffeneau index. Results: there weren’t significant differences between VC, FEV1 and Tiffeneau indexes of students in both sexes of 2 regions (p<0.05). There is a close correlation between VC and height of student (r>0.9), and between FEV1 and height (r>0.9)
Preventive Medicine ; Public Health ; Alkalosis, Respiratory