Progressive increase of serum zinc level in a Pediatric patient with PSTPIP1- p.N236K mutation

IF 2.9 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta Pub Date : 2025-10-08 DOI:10.1016/j.cca.2025.120646

Cyrus Takahashi , Devon Rotramel , Rejwi A. Dahal , Amani Dickenson , John O. Ogunbileje

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引用次数: 0

Abstract

Background

Mutations of the cytoskeletal protein proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) are associated with a spectrum of rare autoinflammatory disorders, including PAPA (Pyogenic Arthritis, Pyoderma gangrenosum, and Acne) and PAMI (PSTPIP1-associated myeloid-related inflammatory) syndromes, characterized by various dermatologic and hematologic abnormalities. Mechanistically, this has been linked to an increased affinity for pyrin, leading to autoinflammation and caspase-1 activation. We present a case report of a rare missense PSTPIP1 variant not previously associated with clinically significant findings.

Case Report and Results

The patient is a full-term Caucasian male who presented shortly after birth with pancytopenia in the setting of presumed bacterial meningitis. Whole genome sequencing identified a c.708C > G, p.N236K missense mutation in PSTPIP1, which is not present in the population database gnomAD. A similar c.708C > A, p.N236K variant is classified as being of uncertain significance on ClinVar (Variation ID: 1022810) based on a single submission, but is not currently linked to PAMI syndrome. This patient further demonstrated a progressive increase in serum zinc concentrations and autoinflammation markers.

Conclusion

This case report provides support for other pathogenic PSTPIP1 mutations associated with PAMI syndrome with a progressive increase in zinc and autoinflammation biomarkers. Furthermore, it addresses difficulties in establishing the diagnosis. It emphasizes the utility of molecular testing when faced with inexplicable clinical presentations and the need for an integrated diagnostic algorithm for PAMI.

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PSTPIP1- p.N236K突变患儿血清锌水平进行性升高

细胞骨架蛋白脯氨酸-丝氨酸-苏氨酸磷酸酶相互作用蛋白1 （PSTPIP1）的突变与一系列罕见的自身炎症性疾病有关，包括PAPA（化脓性关节炎、坏疽性脓皮病和痤疮）和PAMI （PSTPIP1相关的髓系炎症）综合征，其特征是各种皮肤和血液异常。从机制上讲，这与pyrin的亲和力增加有关，导致自身炎症和caspase-1激活。我们提出了一个罕见的错义PSTPIP1变异的病例报告，以前没有与临床显著的发现相关。病例报告和结果该患者是一名足月白人男性，出生后不久出现全血细胞减少症，推测为细菌性脑膜炎。全基因组测序发现PSTPIP1中存在c.708C >； G, p.N236K错义突变，该突变在种群数据库gnomAD中不存在。一个类似的c.708C >； A, p.N236K变异基于单一提交被归类为对ClinVar（变异ID: 1022810）具有不确定意义，但目前与PAMI综合征无关。该患者进一步表现出血清锌浓度和自身炎症标志物的进行性增加。结论本病例报告支持其他致病性PSTPIP1突变与PAMI综合征相关，并伴有锌和自身炎症生物标志物的进行性增加。此外，它解决了建立诊断的困难。它强调分子测试的效用时，面对莫名其妙的临床表现和需要一个综合诊断算法的PAMI。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinica Chimica Acta 医学-医学实验技术

CiteScore

10.10

自引率

2.00%

发文量

1268

审稿时长

23 days

期刊介绍： The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells. The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.