Compound heterozygous p.L483P and p.S310G mutations in GBA1 cause type 1 adult Gaucher disease: A case report.

BACKGROUND: Gaucher disease (GD) is caused by a GBA1 gene mutation that leads to decreased acid ß-glucosidase activity [glucocerebrosidase (GCase)]. This study aimed to identify and characterise compound heterozygous mutations in GBA1 in a patient with type 1 GD. CASE SUMMARY: Here, we report a rare adult-onset type 1 GD in a 46-year-old female patient with clinical manifestations of giant spleen, thrombocytopenia, and bone pain, diagnosed by enzymatic and genetic testing. Enzymology and whole exome sequencing revealed heterozygous missense mutations in exon 10 c.1448T>C (p.L483P) and exon 7 c.928A>G (p.S310G) of GBA1. The latter was first reported in patients with GD. Structural modelling showed that p.S310G and p.L483P were distant from the GCase active site. The p.S310G mutation in domain 1 may decrease stability between the α2 and α3 helices of GBA1. The p.L483P mutation in domain 2 reduced the van der Waals force of the side chain and disrupted the C-terminal ß-sheet. The patient was treated with imiglucerase replacement therapy, and her condition was stable. CONCLUSION: The p.L483P/p.S310G novel compound heterozygous mutation underlies type 1 GD and likely affects GCase protein function. This is the first description of p.S310G being associated with mild type 1 GD in the context of a coinherited p.L483P mutation.

[Levels of regulatory T cells in peripheral blood of children with idiopathic thrombocytopenic purpura].

OBJECTIVE: To study the levels of CD4+CD25+CD127- and CD3+CD4-CD8- regulatory T (Treg) cells in peripheral blood of children with idiopathic thrombocytopenic purpura (ITP). METHODS: The flow cytometry was used to detect the expression of CD4+CD25+CD127- and CD3+CD4-CD8- Treg cells in peripheral blood of 33 children with ITP and 21 healthy children. RESULTS: The expression levels of CD4+CD25+CD127-ï¼»(2.7±1.7)% vs (4.8±1.6)%; P<0.01ï¼½and CD3+CD4-CD8-ï¼»(5.2±3.1)% vs (8.1±3.5)%; P<0.01ï¼½Treg cells in children with ITP were significantly lower than in the controls. CONCLUSIONS: The expression levels of CD4+CD25+CD127- and CD3+CD4-CD8- Treg cells decrease in children with ITP, suggesting that CD4+CD25+CD127- and CD3+CD4-CD8- Treg cells might play a role in the pathogenesis of ITP.

[Clinical experience of successful management of a child with A/H5N1 infection in Shanxi province].

OBJECTIVE: To explore the clinical features and treatment strategy of human influenza A (H5N1) virus infection. METHODS: The clinical data from a 2-year-old girl with A/H5N1 infection were collected and analyzed. RESULTS: The patient had a history of exposure to a living poultry market. A/H5N1 nucleic acid was detected by real-time polymerase chain reaction and reverse-transcription polymerase chain reaction in a nasopharyngeal aspirate. The prominent clinical features included fever, cough and dyspnea. Extensive multiple lobular infiltrates developed quickly, followed by acute respiratory distress syndrome (ARDS) and multi-organ dysfunction. Corticosteroids, oxygen therapy and non-invasive mechanical ventilation were administrated on day 9 after onset of the disease. The patient's condition became stable after the management. After A/H5N1 infection was confirmed, antiviral treatment with oseltamivir and A/H5N1 vaccinated plasma were used on day 11. Oxygenation and serum enzyme levels returned to normal gradually, and most of the lung infiltrates disappeared. The patient was discharged on day 28. CONCLUSION: Human A/H5N1 infection is a severe and rapidly progressive disease mostly manifested as ARDS. Corticosteroids may have some effects on the pulmonary lesions, but oxygen therapy and ventilatory support are the mainstay of the management. A/H5N1 vaccinated plasma may be useful for improving the prognosis.