Niemann-Pick disease type C (NP-C) is a rare autosomal recessive neurovisceral lysosomal lipid storage disorder. The clinical manifestations of the disorder are variable. This report describes the case of a 27-month-old girl with NP-C whose condition had been misdiagnosed as spastic cerebral palsy (CP). She had spasticity, particularly at both ankles, and gait disturbance. Magnetic resonance imaging of the brain revealed findings suspicious of sequelae from a previous insult, such as periventricular leukomalacia, leading to the diagnosis of CP. However, she had a history of hepatosplenomegaly when she was a fetus and her motor development had deteriorated, with symptoms of vertical supranuclear gaze palsy, cataplexy, and ataxia developing gradually. Therefore, NP-C was considered and confirmed with a genetic study, which showed mutation of the NPC1 gene. Thus, if a child with CP-like symptoms presents with a deteriorating course and NP-C-specific symptoms, NP-C should be cautiously considered.
Ankle ; Ataxia ; Brain ; Cataplexy ; Cerebral Palsy ; Child ; Child, Preschool ; Diagnosis ; Female ; Fetus ; Gait ; Humans ; Infant, Newborn ; Leukomalacia, Periventricular ; Magnetic Resonance Imaging ; Muscle Spasticity ; Niemann-Pick Diseases ; Paralysis

OBJECTIVE: To noninvasively assess the neurodegenerative changes in the brain of patients with Niemann-Pick type C (NPC) disease by measuring the lesion tissue with the iterative decomposition of water and fat with echo asymmetry and least square estimation-iron quantification (IDEAL-IQ). MATERIALS AND METHODS: Routine brain MRI, IDEAL-IQ and 1H-proton magnetic resonance spectroscopy (1H-MRS, served as control) were performed on 12 patients with type C Niemann-Pick disease (4 males and 8 females; age range, 15–61 years; mean age, 36 years) and 20 healthy subjects (10 males and 10 females; age range, 20–65 years; mean age, 38 years). The regions with lesion and the normal appearing regions (NARs) of patients were measured and analyzed based on the fat/water signal intensity on IDEAL-IQ and the lipid peak on 1H-MRS. RESULTS: Niemann-Pick type C patients showed a higher fat/water signal intensity ratio with IDEAL-IQ on T2 hyperintensity lesions and NARs (3.7–4.9%, p < 0.05 and 1.8–3.0%, p < 0.05, respectively), as compared to healthy controls (HCs) (1.2–2.3%). After treatment, the fat/water signal intensity ratio decreased (2.2–3.4%), but remained higher than in the HCs (p < 0.05). The results of the 1H-MRS measurements showed increased lipid peaks in the same lesion regions, and the micro-lipid storage disorder of NARs in NPC patients was detectable by IDEAL-IQ instead of 1H-MRS. CONCLUSION: The findings of this study suggested that IDEAL-IQ may be useful as a noninvasive and objective method in the evaluation of patients with NPC; additionally, IDEAL-IQ can be used to quantitatively measure the brain parenchymal adipose content and monitor patient follow-up after treatment of NPC.
Brain ; Female ; Follow-Up Studies ; Healthy Volunteers ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Male ; Methods ; Niemann-Pick Diseases ; Proton Magnetic Resonance Spectroscopy ; Water

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

Clinical Laboratory Techniques ; Diagnosis, Differential ; Humans ; Niemann-Pick Diseases ; diagnosis

Humans ; Niemann-Pick Diseases ; Stomach Neoplasms

BACKGROUND AND OBJECTIVES: Niemann Pick A disease causes a progressive accumulation of sphyngomyelin in several organs and the survival of the patients is usually limited to three years. We describe the outcome of a patient suffering from Niemann Pick A disease, who first underwent an haploidentical bone marrow transplantation, and then intrathecal and I.V injections of mesenchymal cells. METHODS AND RESULTS: While the outcome of bone marrow transplantation was a complete failure, one month after the treatment with the mesenchymal cells the patient improved from the psychomotor and the parenchymal storage perspective. When hypersplenism was solved platelets rose quickly from 20,000 to 120,000/microliter. CONCLUSIONS: Therefore cellular therapy should be considered as a possible choice of treatment of NPA disease.
Bone Marrow Transplantation ; Humans ; Hypersplenism ; Niemann-Pick Diseases* ; Stem Cells*

Child, Preschool ; Graft vs Host Disease ; prevention & control ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Niemann-Pick Diseases ; therapy ; Transplantation, Homologous

Adolescent ; Adult ; Female ; Humans ; Male ; Niemann-Pick Diseases ; genetics ; Pedigree

OBJECTIVEChitotriosidase (CT) is a plasma biomarker for Gaucher disease (GD), the enzyme activity is usually markedly elevated in plasma of Gaucher patients, and it was reported that levels of plasma chitotriosidase activity was mildly-moderately increased in patients with Niemann-Pick disease (NPD). The aim of this study was to compare chitotriosidase activity using 4-methylumbelliferyl-β-D-N, N', N″-triacetyl-chitotrioside (4MU-C3) with 4-methylumbelliferyl 4-deoxy-β-D-chitobiose (4MU-4dC2) as substrates, and apply chitotriosidase activity measurement to help clinical determination of GD and NPD, and to monitor therapy in GD patients.

METHODPlasma of 45 healthy individuals, 31 patients with GD and 9 patients with NPD type A/B was collected from outpatient clinics of the Department of Pediatric Endocrinologic, Genetic and Metabolic Diseases, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Plasma chitotriosidase activity was measured with the substrates 4MU-C3 and 4MU-4dC2 respectively. Determinations were based on the methods described by Hollak et al and Rodrigues et al. Meanwhile, common mutation dup24 of the human chitotriosidase gene was detected.

RESULT(1) Chitotriosidase activity when measured with 4MU-4dC2 gave higher values than 4MU-C3. In the healthy controls chitotriosidase activity was increased 3.7-fold when the 4MU-dC2 was used as substrate as compared with the 4MU-C3 (Z = -4.703, P < 0.001). In the untreated GD patients, the median value was increased 794-fold and 610-fold of the control subjects (Z = -3.823, P < 0.001) when the enzyme was measured with two substrates respectively. In the GD patients during therapy, chitotriosidase activity was increased 134-fold and 79-fold, and after changing therapeutic dose chitotriosidase activity was increased 215-fold and 118-fold of the controls (Z = -2.521, P < 0.05). In the NPD patients chitotriosidase activity was increased 8-fold and 14-fold of the controls (Z = -1.604, P = 0.109). (2) Consistent with the results of chitotriosidase activity, 30 of 85 (35.3%) individuals were homozygotes of dup24 mutation, which are completely chitotriosidase enzyme deficiency. Among GD patients with wild-type and heterozygotes for the dup24 mutation, chitotriosidase activity highly increased in the plasma compared with the controls.

CONCLUSIONThe use of 4MU-4dC2 as substrate makes chitotriosidase activity measurement more sensitive. The determination of plasma chitotriosidase activity is a useful tool to assist the clinical identification of Gaucher disease, and to monitor enzyme replacement therapy (ERT) of non-chitotriosidase deficient GD patients. Chitotriosidase activity determination has no value in the clinical identification of NPD.

Adolescent ; Adult ; Blood Chemical Analysis ; methods ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Gaucher Disease ; blood ; enzymology ; genetics ; Genotype ; Heterozygote ; Hexosaminidases ; blood ; genetics ; metabolism ; Humans ; Infant ; Male ; Middle Aged ; Mutation ; Niemann-Pick Diseases ; blood ; enzymology ; genetics ; Polymerase Chain Reaction ; Sensitivity and Specificity ; Young Adult

Niemann-Pick disease (NPD) is an autosomal recessive, lipid storage disorder caused by the deficiency of the lysosomal enzyme sphingomyelinase or defective cholesterol transport from lysosome to cytosol. The clinical symptoms and signs include dysphagia, loss of motor function, hepatosplenomegaly, recurred respiratory infections, seizure, mental retardation, spasticity, myoclonic jerks and ataxia, but vary depending on the type of this disease. We report a successful anesthetic experience, including endotracheal intubation with Glidescope under propofol and remifentanil infusion without neuromuscular blockade, in a 21-year old woman with Niemann-Pick disease for wound revision of gastrostomy site.
Ataxia ; Cholesterol ; Cytosol ; Deglutition Disorders ; Female ; Gastrostomy ; Humans ; Intellectual Disability ; Intubation, Intratracheal ; Lysosomes ; Muscle Spasticity ; Myoclonus ; Neuromuscular Blockade ; Niemann-Pick Diseases ; Piperidines ; Propofol ; Respiratory Tract Infections ; Seizures ; Sphingomyelin Phosphodiesterase