更新于：2024-11-01

Infantile multisystem neurologic-endocrine-pancreatic disease

婴儿期发病的多系统疾病（神经系统、内分泌系统和胰腺系统疾病）

更新于：2024-11-01

基本信息

别名

IMNEPD、IMNEPD1、Infantile multisystem neurologic-endocrine-pancreatic disease

+ [2]

简介

A rare multiple congenital anomalies/dysmorphic syndrome with intellectual disability characterized by global developmental delay, postnatal microcephaly, intellectual disability, ataxia, sensorineural hearing loss, and exocrine pancreatic insufficiency. More variable manifestations include hypotonia, growth retardation, peripheral demyelinating neuropathy, dysmorphic facial features, and additional endocrine abnormalities. Brain imaging may show progressive cerebellar atrophy in some patients.

关联

项与婴儿期发病的多系统疾病（神经系统、内分泌系统和胰腺系统疾病）相关的药物

Iptacopan

盐酸伊普可泮

靶点

CFB

作用机制

CFB抑制剂

在研机构

Novartis Pharma Produktions GmbH [+11]

原研机构

Novartis Pharma AG

在研适应症

免疫球蛋白a肾病 [+14]

非在研适应症

冷凝集素病 [+6]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2023-12-05

Resomelagon

靶点

MC1R x MC3R

作用机制

MC1R激动剂 [+1]

在研机构

SynAct Pharma ApS

原研机构

SynAct Pharma AB

在研适应症

肾病综合征 [+5]

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

项与婴儿期发病的多系统疾病（神经系统、内分泌系统和胰腺系统疾病）相关的临床试验

NCT05514470 / Not yet recruitingN/AIIT

Impact of Loss-of-function Mutations of Genes Encoding Cytosolic Aminoacyl-tRNA Synthetases on Protein Translation and Responses to Cellular Stress

Mutations in the genes encoding cytosolic aminoacyl-tRNA synthetases are responsible for early-onset multisystemic diseases including to varying degrees interstitial lung disease, liver damage, neurological and digestive disorders, and systemic inflammation. These are rare and severe diseases whose pathophysiology is poorly understood.
The investigative team hypothesizes that mutations within these genes are responsible for a decrease in protein translation and lead to a cellular stress response similar to that induced by amino acid deprivation. The investigative team also hypothesizes that these alterations could be corrected by high-dose supplementation in the culture medium of the corresponding amino acid.
The main objective of the study is to precisely determine the consequences of cytosolic aminoacyl-tRNA synthetase mutations at the cell level on protein translation.

开始日期2024-11-01

申办/合作机构

Assistance Publique des Hôpitaux de Paris SA

NCT05850845 / Not yet recruitingN/AIIT

Study on the Application of Hyperspectral Imaging Technique in CTX Treatment of IMN

Investigators propose hyperspectral imaging analysis as a method to distinguish the efficacy of hormone-combined cyclophosphamide therapy for PMN, and classify sensitive and insensitive patients treated with hormone-combined cyclophosphamide regimen. A variety of machine learning models were used to prove that hyperspectral imaging technology could assist patients in selecting the optimal treatment plan, and further explore the predictive indicators of PMN treatment effect.

开始日期2023-06-25

申办/合作机构

山东省千佛山医院

NCT05797038 / Not yet recruitingN/AIIT

Study on the Application of Hyperspectral Imaging Technique in the Treatment of TAC

We propose hyperspectral imaging analysis as a method to identify the efficacy of hormone-tacrolimus therapy for PMN, and to classify sensitive and insensitive patients treated with hormone-tacrolimus regimen. A variety of machine learning models were used to prove that hyperspectral imaging technology could assist patients in selecting the optimal treatment plan, and further explore the predictive indicators of PMN treatment effect.

开始日期2023-04-25

申办/合作机构

山东省千佛山医院

100 项与婴儿期发病的多系统疾病（神经系统、内分泌系统和胰腺系统疾病）相关的临床结果

登录后查看更多信息

100 项与婴儿期发病的多系统疾病（神经系统、内分泌系统和胰腺系统疾病）相关的转化医学

登录后查看更多信息

0 项与婴儿期发病的多系统疾病（神经系统、内分泌系统和胰腺系统疾病）相关的专利（医药）

登录后查看更多信息

项与婴儿期发病的多系统疾病（神经系统、内分泌系统和胰腺系统疾病）相关的文献（医药）

2024-06-01·Journal of the Peripheral Nervous System

The neurological core features of the infantile‐onset multisystem neurologic, endocrine, and pancreatic disease: A novel nonsense mutation in an Italian family

Article

作者: Gotta, Fabio ; La Barbera, Andrea ; Marsico, Oreste ; Geroldi, Alessandro ; Mammi, Alessia ; Sanguineri, Francesca ; Origone, Paola ; Mandich, Paola ; Patrone, Serena ; Bellone, Emilia ; Ponti, Clarissa ; Iacomino, Michele ; Ferlazzo, Edoardo ; Pascarella, Angelo ; Schenone, Angelo ; Traverso, Monica ; Gaudio, Andrea

AbstractAimBiallelic mutations in the PTRH2 gene have been associated with infantile multisystem neurological, endocrine, and pancreatic disease (IMNEPD), a rare autosomal recessive disorder of variable expressivity characterized by global developmental delay, intellectual disability or borderline IQ level, sensorineural hearing loss, ataxia, and pancreatic insufficiency. Various additional features may be included, such as peripheral neuropathy, facial dysmorphism, hypothyroidism, hepatic fibrosis, postnatal microcephaly, cerebellar atrophy, and epilepsy. Here, we report the first Italian family presenting only predominant neurological features.MethodsExtensive neurological and neurophysiological evaluations have been conducted on the two affected brothers and their healthy mother since 1996. The diagnosis of peripheral neuropathy of probable hereditary origin was confirmed through a sural nerve biopsy. Exome sequencing was performed after the analysis of major neuropathy‐associated genes yielded negative results.ResultsWhole‐exome sequencing analysis identified the homozygous substitution c.256C>T (p.Gln86Ter) in the PTRH2 gene in the two siblings. According to American College of Medical Genetics and Genomics (ACMG) guidelines, the variant has been classified as pathogenic.At 48 years old, the proband's reevaluation confirmed a demyelinating sensorimotor polyneuropathy with bilateral sensorineural hearing loss that had been noted since he was 13. Additionally, drug‐resistant epileptic seizures occurred when he was 32 years old. No hepatic or endocrinological signs developed. The younger affected brother, 47 years old, has an overlapping clinical presentation without epilepsy.InterpretationOur findings expand the clinical phenotype and further demonstrate the clinical heterogeneity related to PTRH2 variants. We thereby hope to better define IMNEPD and facilitate the identification and diagnosis of this novel disease entity.

2023-05-01·Clinical and experimental pediatrics

Novel PTRH2 gene variant causing IMNEPD (infantile-onset multisystem neurologic, endocrine, and pancreatic disease) in 2 Saudi siblings.

Article

作者: Bubshait, Dalal K

2023-04-30·Genes

PTRH2 Gene Variants: Recent Review of the Phenotypic Features and Their Bioinformatics Analysis.

Article

作者: Azem, Abdussalam ; Jain, Sahil ; Habib, Clair ; Zalan, Abdelnaser ; Al-Shareef, Wasif ; Sharkia, Rajech ; Mahajnah, Muhammad

Peptidyl-tRNA hydrolase 2 (PTRH2) is an evolutionarily highly conserved mitochondrial protein. The biallelic mutations in the PTRH2 gene have been suggested to cause a rare autosomal recessive disorder characterized by an infantile-onset multisystem neurologic endocrine and pancreatic disease (IMNEPD). Patients with IMNEPD present varying clinical manifestations, including global developmental delay associated with microcephaly, growth retardation, progressive ataxia, distal muscle weakness with ankle contractures, demyelinating sensorimotor neuropathy, sensorineural hearing loss, and abnormalities of thyroid, pancreas, and liver. In the current study, we conducted an extensive literature review with an emphasis on the variable clinical spectrum and genotypes in patients. Additionally, we reported on a new case with a previously documented mutation. A bioinformatics analysis of the various PTRH2 gene variants was also carried out from a structural perspective. It appears that the most common clinical characteristics among all patients include motor delay (92%), neuropathy (90%), distal weakness (86.4%), intellectual disability (84%), hearing impairment (80%), ataxia (79%), and deformity of head and face (~70%). The less common characteristics include hand deformity (64%), cerebellar atrophy/hypoplasia (47%), and pancreatic abnormality (35%), while the least common appear to be diabetes mellitus (~30%), liver abnormality (~22%), and hypothyroidism (16%). Three missense mutations were revealed in the PTRH2 gene, the most common one being Q85P, which was shared by four different Arab communities and was presented in our new case. Moreover, four different nonsense mutations in the PTRH2 gene were detected. It may be concluded that disease severity depends on the PTRH2 gene variant, as most of the clinical features are manifested by nonsense mutations, while only the common features are presented by missense mutations. A bioinformatics analysis of the various PTRH2 gene variants also suggested the mutations to be deleterious, as they seem to disrupt the structural confirmation of the enzyme, leading to loss of stability and functionality.