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Case Report: Be Aware of "New" Features of Niemann-Pick Disease: Insights From Two Pediatric Cases.

ABSTRACT: Niemann-Pick disease is a relatively common lysosomal storage disease. Cholestatic liver disease is a typical clinical phenotype of Niemann-Pick disease in infancy. The diagnosis is traditionally based on Niemann-Pick cells in bone marrow smears or liver biopsies. Treatment for cholestatic liver disease mainly includes ursodeoxycholic acid and liver protection drugs. Here, we reported two cases of Niemann-Pick disease type C, diagnosed by genetic analysis during early infancy. Besides cholestatic jaundice, the two patients also exhibited signs of immune system hyperactivity, such as elevated immunoglobulins or multiple autoantibodies, which might require the application of glucocorticoids. In addition, three novel missense variants of the NPC1 gene were identified. The findings suggest that immune activation should be considered as a "new" clinical phenotype of lysosomal storage diseases.

SUBMITTER: Chen F

PROVIDER: S-EPMC8961870 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Case Report: Be Aware of "New" Features of Niemann-Pick Disease: Insights From Two Pediatric Cases.

Chen Fan F Guo Shan S Li Xuesong X Liu Shengxuan S Wang Li L Zhang Victor Wei VW Xu Hui H Huang Zhihua Z Ying Yanqin Y Shu Sainan S

Frontiers in genetics 20220311

Niemann-Pick disease is a relatively common lysosomal storage disease. Cholestatic liver disease is a typical clinical phenotype of Niemann-Pick disease in infancy. The diagnosis is traditionally based on Niemann-Pick cells in bone marrow smears or liver biopsies. Treatment for cholestatic liver disease mainly includes ursodeoxycholic acid and liver protection drugs. Here, we reported two cases of Niemann-Pick disease type C, diagnosed by genetic analysis during early infancy. Besides cholestati ...[more]

PMID: 35360843

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Project description:BACKGROUND:Niemann-Pick disease type C (NPC) is a lysosomal storage disorder with severe prognosis. Disease-specific therapy is crucial to prevent disease progression; however, diagnosing NPC is quite difficult because of remarkably variable clinical presentations. The NPC Suspicion Index (NPC-SI) was developed to overcome this problem. Identifying preclinical cases is important for prevention and therapy. Here, we report three newly diagnosed NPC cases, one typical juvenile-onset case and the cases of two sisters with symptoms neurologically/psychiatrically indistinguishable from dystonia and schizophrenia, respectively. CASE PRESENTATION:In Case 1, a 25-year-old man presented with a 14-year history of intellectual disability, clumsiness, spastic ataxia, dysphagia, and frequent falls. Neurological examination revealed vertical supranuclear gaze palsy and involuntary movements. Ultrasonography revealed mild splenomegaly, and filipin staining of skin fibroblasts was positive with a variant staining pattern. NPC1 gene analysis showed compound heterozygous mutations, including c.1421C?>?T (p.P474L), a known causative mutation, and c.3722 T?>?C (p.L1241S), a new mutation. In Case 2, a 28-year-old woman, the proband, who had marked splenomegaly in her childhood, survived well, contrary to the expected severe prognosis of infantile NPC. She had minor neuropsychiatric symptoms including auditory hallucinations, nocturnal urination, and sleep paralysis. At the age of 28 years, she presented with a 1-year history of orofacial and oromandibular painful dystonia. The patient's 35-year-old sister (Case 3) was diagnosed with schizophrenia. In both cases, filipin staining of skin fibroblasts was positive with variant staining patterns, as well as elevated levels of urinary bile acids. NPC1 gene analysis showed compound heterozygous mutations including c.3011C?>?T (p.S1004 L), a known causative mutation, and c.160_161insG (p.D54GfsX4), a new mutation. Their mother, who was under therapy with modafinil for narcolepsy, shared the latter mutation. CONCLUSIONS:Marked clinical variability was observed in our three cases. NPC could masquerade as a pure neuropsychiatric disorder such as dystonia or schizophrenia. Abdominal ultrasonography, history evaluation, and neurological examination were quite important in the diagnostic process.

Dataset Information

Case Report: Be Aware of "New" Features of Niemann-Pick Disease: Insights From Two Pediatric Cases.

Publications

Case Report: Be Aware of "New" Features of Niemann-Pick Disease: Insights From Two Pediatric Cases.

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