Dataset Information

Variant Type X91⁺ Chronic Granulomatous Disease: Clinical and Molecular Characterization in a Chinese Cohort.

ABSTRACT:

Purpose

We aimed to report the clinical and immunological characteristics of variant type X91⁺ chronic granulomatous disease (CGD) in a Chinese cohort.

Methods

The clinical manifestations and immunological phenotypes of patients with X91⁺ CGD were collected. A dihydrorhodamine (DHR) analysis was performed to evaluate neutrophil function. Gp91^phox protein expression was determined using extracellular staining with the monoclonal antibody (mAb) 7D5 and flow cytometry.

Results

Patients with X91⁺ CGD accounted for 8% (7/85) of all patients with CGD. The median age of onset in the seven patients with X91⁺ CGD was 4 months. Six patients received the BCG vaccine, and 50% (3/6) had probable BCG infections. Mycobacterium tuberculosis infection was prominent. The most common sites of infection were the lung (6/7), lymph nodes (5/7), and soft tissue (3/7). Two patients experienced recurrent oral ulcers. The stimulation index (SI) of the patients with X91⁺ CGD ranged widely from 1.9 to 67.3. The difference in the SI among the three groups of patients (X91⁺ CGD, X91^- CGD, and X91⁰ CGD) was statistically significant (P = 0.0071). The three groups showed no significant differences in onset age, diagnosis age, or severe infection frequency. CYBB mutations associated with X91⁺ CGD were commonly located in the second transmembrane or intracellular regions. Three novel X91⁺ CGD-related mutations (c.1462-2 A > T, c.1243C > T, and c.925G > A) were identified.

Conclusions

Variant type X91⁺ CGD may result in varied clinical manifestations. Moreover, the laboratory findings might indicate a moderate neutrophil SI. We should deepen our understanding of variant X91⁺ CGD to prevent missed diagnoses.

SUBMITTER: Sun B

PROVIDER: S-EPMC9674757 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Variant Type X91<sup>+</sup> Chronic Granulomatous Disease: Clinical and Molecular Characterization in a Chinese Cohort.

Sun Bijun B Zhu Zeyu Z Hui Xiaoying X Sun Jinqiao J Wang Wenjie W Ying Wenjing W Zhou Qinhua Q Yao Haili H Hou Jia J Wang Xiaochuan X

Journal of clinical immunology 20220707 7

<h4>Purpose</h4>We aimed to report the clinical and immunological characteristics of variant type X91<sup>+</sup> chronic granulomatous disease (CGD) in a Chinese cohort.<h4>Methods</h4>The clinical manifestations and immunological phenotypes of patients with X91<sup>+</sup> CGD were collected. A dihydrorhodamine (DHR) analysis was performed to evaluate neutrophil function. Gp91<sup>phox</sup> protein expression was determined using extracellular staining with the monoclonal antibody (mAb) 7D5 a ...[more]

PMID: 35796921

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Project description:Background and objectivesThis retrospective study analysed a case series of subjects with citrin deficiency, and aims to present the molecular and clinical characterization of this disease in the Hong Kong Chinese population for the first time.Patients and methodsData from medical records of eighteen patients with citrin deficiency (years 2006-2015) were retrieved. Demographic data, biochemical parameters, radiological results, genetic testing results, management, and clinical outcome were collected and analysed.ResultsEighteen patients with diagnosis of citrin deficiency were recruited. All 18 patients carried at least one common pathogenic variant c.852_855delTATG in SLC25A13. Prolonged jaundice (neonatal intrahepatic cholestasis caused by citrin deficiency, NICCD) was the most common presenting symptom, in conjunction with elevated plasma citrulline, threonine, alkaline phosphatase, and alpha-fetoprotein levels. The abnormal biochemical parameters including liver derangement returned to normal range in most of the cases by 6 months of age after the introduction of a lactose-free formula. There were a few cases with atypical presentations. Two subjects did not present with NICCD, and were subsequently diagnosed later in life after their siblings presented with symptoms of citrin deficiency at one month of age and subsequently received a molecular diagnosis. One patient with citrin deficiency also exhibited multiple liver hemangioendotheliomas, which subsided gradually after introduction of a lactose-free formula. Only one patient from this cohort was offered expanded metabolic screening at birth. She was not ascertained by conducted newborn screening and was diagnosed upon presentation with cholestatic jaundice by 1 month of age.ConclusionThis is the first report of the clinical and molecular characterization of a large cohort of patients with citrin deficiency in Hong Kong. The presentation of this cohort of patients expands the clinical phenotypic spectrum of NICCD. Benign liver tumors such as hemangioendotheliomas may be associated with citrin deficiency in addition to the well-known association with hepatocellular carcinoma. Citrin deficiency may manifest in later infancy period with an NICCD-like phenotype. Furthermore, this condition is not always ascertained by expanded newborn metabolic screening testing.

Project description:BackgroundChronic granulomatous disease (CGD) is an inherited defect in phagocytic respiratory burst that results in severe and life-threatening infections in affected children. Single center studies from India have shown that proportion of autosomal recessive (AR) CGD is more than that reported from the West. Further, affected patients have high mortality rates due to late referrals and difficulties in accessing appropriate treatment. However, there is lack of multicentric collaborative data on CGD from India.ObjectiveTo describe infection patterns, immunological, and molecular features of CGD from multiple centers in India.MethodsA detailed proforma that included clinical and laboratory details was prepared and sent to multiple centers in India that are involved in the care and management of patients with inborn errors of immunity. Twelve centers have provided data which were later pooled together and analyzed.ResultsOf the 236 patients analyzed in our study, X-linked and AR-CGD was seen in 77 and 97, respectively. Male female ratio was 172:64. Median age at onset of symptoms and diagnosis was 8 and 24 months, respectively. Common infections documented include pneumonia (71.6%), lymphadenitis (31.6%), skin and subcutaneous abscess (23.7%), blood-stream infection (13.6%), osteomyelitis (8.6%), liver abscess (7.2%), lung abscess (2.9%), meningoencephalitis (2.5%), splenic abscess (1.7%), and brain abscess (0.9%). Forty-four patients (18.6%) had evidence of mycobacterial infection. Results of molecular assay were available for 141 patients (59.7%)-CYBB (44.7%) gene defect was most common, followed by NCF1 (31.9%), NCF2 (14.9%), and CYBA (8.5%). While CYBA variants were documented only in Southern and Western parts of India, a common dinucleotide deletion in NCF2 (c.835_836delAC) was noted only in North Indian population. Of the 174 patients with available outcome data, 67 (38.5%) had expired. Hematopoietic stem cell transplantation was carried out in 23 patients, and 12 are doing well on follow-up.ConclusionsIn India, proportion of patients with AR-CGD is higher as compared to Western cohorts, though regional differences in types of AR-CGD exist. Clinical profile and mortality rates are similar in both X-linked and AR-CGD. However, this may be a reflection of the fact that milder forms of AR-CGD are probably being missed.

Dataset Information

Variant Type X91⁺ Chronic Granulomatous Disease: Clinical and Molecular Characterization in a Chinese Cohort.

Purpose

Methods

Results

Conclusions

Publications

Variant Type X91<sup>+</sup> Chronic Granulomatous Disease: Clinical and Molecular Characterization in a Chinese Cohort.

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Dataset Information

Variant Type X91+ Chronic Granulomatous Disease: Clinical and Molecular Characterization in a Chinese Cohort.

Purpose

Methods

Results

Conclusions

Publications

Variant Type X91<sup>+</sup> Chronic Granulomatous Disease: Clinical and Molecular Characterization in a Chinese Cohort.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Variant Type X91⁺ Chronic Granulomatous Disease: Clinical and Molecular Characterization in a Chinese Cohort.