Abdulkarim Boraan, Mittal Setu, Vahidnezhad Hassan, Davis Dawn Marie, Camilleri Michael J, Mohandesi Nessa Aghazadeh
University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Department of Dermatology, Mayo Clinic, Rochester, Minnesota, USA.
Pediatr Dermatol. 2025 Mar-Apr;42(2):233-239. doi: 10.1111/pde.15868. Epub 2025 Jan 31.
Nicotinamide adenine dinucleotide phosphate hydrate dehydratase (NAXD) and nicotinamide adenine dinucleotide phosphate hydrate epimerase (NAXE) deficiencies are rare autosomal recessive metabolic disorders characterized by severe neurological manifestations during infancy. In affected individuals, febrile illnesses can trigger progressive encephalopathy often accompanied by distinctive skin eruptions, resulting in high mortality rates. This study reviews the literature on NAXD/NAXE deficiencies, focusing on dermatological manifestations and their correlation with genotypic variations and treatment responses. A comprehensive literature search identified 45 patients with 31 pathogenic/likely pathogenic mutations, and a median age of onset at 1.16 years. Patients with NAXE deficiency exhibited a broader range of age of symptom onset compared to those affected with NAXD deficiency. Fever or infections were identified as the most common triggers for decompensation episodes. Skin manifestations were observed in 31% of patients with whole cell NAXD and NAXE deficiencies. The characteristic skin eruption comprises well-demarcated erythematous and erosive plaques progressing to blistering and necrosis, predominantly affecting flexural surfaces. The mortality rate was 78%, with survivors experiencing varying degrees of neurological sequelae. Niacin/nicotinamide supplementation resulted in improvements in skin lesions and survival rates. The review underscores the critical role of dermatologists in early diagnosis and intervention of NAXE and NAXD deficiencies. Recognizing characteristic skin manifestations is essential, particularly in patients with acute neurological decline following infections or vaccinations. Early intervention with specific supplements shows promise; however, further research is needed to establish standardized treatment protocols and enhance patient outcomes.
烟酰胺腺嘌呤二核苷酸磷酸水合物脱水酶（NAXD）和烟酰胺腺嘌呤二核苷酸磷酸水合物表异构酶（NAXE）缺乏症是罕见的常染色体隐性代谢障碍，其特征为婴儿期出现严重的神经学表现。在受影响的个体中，发热性疾病可引发进行性脑病，常伴有独特的皮肤疹，导致高死亡率。本研究回顾了关于NAXD/NAXE缺乏症的文献，重点关注皮肤病学表现及其与基因型变异和治疗反应的相关性。全面的文献检索确定了45例患者，有31种致病/可能致病的突变，中位发病年龄为1.16岁。与NAXD缺乏症患者相比，NAXE缺乏症患者的症状发作年龄范围更广。发热或感染被确定为失代偿发作最常见的诱因。在全细胞NAXD和NAXE缺乏症患者中，31%观察到皮肤表现。特征性皮肤疹包括边界清楚的红斑和糜烂性斑块，进展为水疱和坏死，主要影响屈侧表面。死亡率为78%，幸存者有不同程度神经后遗症。补充烟酸/烟酰胺可改善皮肤病变和生存率。该综述强调皮肤科医生在NAXE和NAXD缺乏症早期诊断和干预中的关键作用。认识特征性皮肤表现至关重要，特别是在感染或接种疫苗后出现急性神经功能衰退的患者中。早期使用特定补充剂进行干预显示出前景；然而，需要进一步研究以建立标准化治疗方案并改善患者结局。
