Berling Edouard, Latour Philippe, Loiselet Klervie, Guémy Clément, Vidoni Léo, Romero Norma B, Lacene Emmanuelle, Evangelista Teresinha, Stojkovic Tanya
From the APHP (E.B., C.G.), Service de Neurologie, Hôpital Raymond Poincaré, Garches; APHP (E.B., C.G.), Centre de référence Nord-Est-Ile-de-France, FHU PHENIX; Université de Versailles Saint-Quentin-en-Yvelines (E.B.), U 1179 INSERM, Paris-Saclay; Centre de Biologie Est (P.L., L.V.), Hospices Civils, Lyon; Department of Pediatric Radiology (K.L.), Hôpital Necker-Enfants Malades, Paris; Sorbonne Université (N.B.R., T.E.), UMRS974, - INSERM, Centre de Recherche en Myologie, Institut de Myologie Paris; APHP (N.B.R., E.L., T.E.), Unité de Morphologie neuromusculaire, Centre de référence des maladies neuromusculaires Nord-Est-Ile-de-France; and APHP (T.S.), Sorbonne Université, Service de Neuromyologie, Centre de référence Nord-Est-Ile-de-France, Institut de Myologie, Hôpital Pitié-Salpêtrière, Paris, France.
Neurol Genet. 2024 Aug 21;10(5):e200178. doi: 10.1212/NXG.0000000000200178. eCollection 2024 Oct.
The objective of this study was to expand the phenotypic spectrum of infantile-onset multisystem neurologic, endocrine, and pancreatic disease type 1 (IMNEPD1) and highlight the importance of analyzing the gene in patients with neuropathy presenting with pancreatic lipomatosis.
Two sisters, aged 73 and 71 years, respectively, presented a severe, length-dependent sensorimotor axonal neuropathy, associated with deafness and intellectual deficiency.
They both needed a wheelchair from the fourth decade. They developed a severe respiratory dysfunction, requiring nocturnal noninvasive ventilation from around 50 years of age. The younger sister developed severe dysphagia complicated by aspiration pneumonia. A muscle biopsy of the younger sister was suggestive of mitochondrial myopathy. The youngest presented a complete pancreatic lipomatosis. A biallelic novel likely pathogenic variant within , c.254A>G (p.Gln85Arg), was evidenced in both patients.
IMNEPD1 is a rare autosomal recessive disorder caused by sequence variant in the gene and characterized by a peripheral neuropathy, cerebellar atrophy, intellectual disability, hearing loss, pancreatic insufficiency, hypothyroidism, and dysmorphic features. In addition to these classic manifestations of the disorder, severe dysphagia and respiratory insufficiency may develop over the course of the disease and should be systematically screened. gene should be considered in patients with pancreatic lipomatosis and neuropathy.
本研究的目的是扩大婴儿期起病的多系统神经、内分泌和胰腺疾病1型（IMNEPD1）的表型谱，并强调对伴有胰腺脂肪化生的神经病变患者进行该基因分析的重要性。
两名分别为73岁和71岁的姐妹表现出严重的、长度依赖性感觉运动轴索性神经病变，伴有耳聋和智力缺陷。
她们在四十多岁时都需要轮椅。她们出现了严重的呼吸功能障碍，从50岁左右开始需要夜间无创通气。妹妹出现严重吞咽困难并并发吸入性肺炎。妹妹的肌肉活检提示线粒体肌病。最年轻的患者表现出完全性胰腺脂肪化生。在两名患者中均发现了位于 内的双等位基因新型可能致病性变异，c.254A>G（p.Gln85Arg）。
IMNEPD1是一种由 基因序列变异引起的罕见常染色体隐性疾病，其特征为周围神经病变、小脑萎缩、智力残疾、听力丧失、胰腺功能不全、甲状腺功能减退和畸形特征。除了该疾病的这些经典表现外，在疾病过程中可能会出现严重吞咽困难和呼吸功能不全，应进行系统筛查。对于伴有胰腺脂肪化生和神经病变的患者，应考虑 基因检测。
