The spectrum of peripheral neuropathy in disorders of the mitochondrial trifunctional protein,Journal of Inherited Metabolic Disease

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The spectrum of peripheral neuropathy in disorders of the mitochondrial trifunctional protein
Journal of Inherited Metabolic Disease ( IF 4.2 ) Pub Date : 2021-02-27 , DOI: 10.1002/jimd.12372
Sarah C Grünert ₁ , Matthias Eckenweiler ₂ , Dorothea Haas ₃ , Martin Lindner ₄ , Konstantinos Tsiakas ₅ , René Santer ₅ , Sara Tucci ₁ , Ute Spiekerkoetter ₁

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Peripheral neuropathy is a known irreversible long-term complication of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and mitochondrial trifunctional protein deficiency (MTPD), two inherited disorders of mitochondrial long-chain fatty acid oxidation. The underlying pathophysiology of neuropathy is still not fully understood. We report electrophysiological studies and neurological findings in a series of 8 LCHAD-deficient and 11 MTP-deficient patients. The median age at time of the study was 8.0 years (0.5-25 years). The overall prevalence of neuropathy was 58% with neuropathic symptoms being slightly more common in MTPD compared to LCHADD (70% vs 50%, respectively). Onset of neuropathy was significantly earlier in MTPD patients compared to LCHADD patients (median age at onset 4.7 vs 15.3 years, respectively, P = .047). In four patients, isolated peripheral neuropathy was the first and only presenting symptom, and in all four the diagnosis was missed by newborn screening. About half of the patients (45.5%) had a sensorimotor neuropathy, while 27.3% showed a pure motor form and another 27.3% an isolated sensory form. Despite early diagnosis by newborn screening and early initiation of therapy, peripheral neuropathy cannot be prevented in all patients with LCHADD/MTPD and has severe impact on the life of affected patients. Electrophysiology classifies LCHADD/MTPD neuropathy as axonal with secondary demyelination. A novel observation is that in patients with acute, fulminant onset of neuropathy, symptoms can be partly reversible. Further studies are needed to elucidate the underlying pathophysiology of axonal damage and possible therapeutic targets.

中文翻译：

线粒体三功能蛋白疾病中的周围神经病变谱

周围神经病变是长链 3-羟酰基辅酶 A 脱氢酶缺乏症 (LCHADD) 和线粒体三功能蛋白缺乏症 (MTPD) 的已知不可逆的长期并发症，这是线粒体长链脂肪酸氧化的两种遗传性疾病。神经病变的潜在病理生理学仍未完全了解。我们报告了一系列 8 名 LCHAD 缺陷和 11 名 MTP 缺陷患者的电生理学研究和神经学发现。研究时的中位年龄为 8.0 岁（0.5-25 岁）。神经病变的总体患病率为 58%，与 LCHADD 相比，神经病变症状在 MTPD 中更常见（分别为 70% 和 50%）。与 LCHADD 患者相比，MTPD 患者的神经病变发病明显更早（发病中位年龄分别为 4.7 岁和 15.3 岁，磷 = .047)。在四名患者中，孤立的周围神经病变是第一个也是唯一的症状，在所有四名患者中，新生儿筛查都漏诊了诊断。大约一半的患者 (45.5%) 有感觉运动神经病，而 27.3% 的患者表现为纯运动形式，另外 27.3% 的患者为孤立的感觉形式。尽管通过新生儿筛查和早期治疗进行早期诊断，但不能在所有 LCHADD/MTPD 患者中预防周围神经病变，并且对受影响患者的生活产生严重影响。电生理学将 LCHADD/MTPD 神经病变分类为轴突伴继发性脱髓鞘。一个新的观察结果是，在急性、暴发性神经病变发作的患者中，症状可以部分可逆。需要进一步的研究来阐明轴突损伤的潜在病理生理学和可能的治疗靶点。

更新日期：2021-02-27

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