Lipoid proteinosis: A case with ophthalmological and psychiatric findings

Lipoid proteinosis (LP) is an uncommon, recessively inherited disorder. The disease usually has its onset in the newborn period and is manifested by hoarseness. The skin and mucous membrane involvement arises between the first and second year of age. A 14-year-old male presented with the complaint of blistering on various sites of his skin, from the age of 12 months, resulting in scarring. Ophthalmological and psychiatric findings also appeared during the clinical course. The histological findings of skin biopsy included extensive deposits of amorphous eosinophilic material in the papillary dermis. No known therapy exists for LP.     

Lipoid proteinosis in two siblings: a report from India

Lipoid proteinosis is an autosomally recessive genodermatosis characterized by widespread deposition of eosinophilic hyaline-like material in the skin, mucous membranes, and other internal organs. Occurrence of lipoid proteinosis in siblings is very rare. We report two siblings from the Indian subcontinent with the classical features of lipoid proteinosis. Both the siblings had had hoarseness of voice and spontaneous vesicular eruptions healing with atrophic scars since their early childhood. They had diffuse waxy thickening of the skin along with beaded papules along the eyelid margin. The tongue was also infiltrated. Skin biopsy demonstrated periodic acid Schiff (PAS) positive eosinophilic material around the blood vessels and appendages.     

Lipoid proteinosis: A case with distinct histopathological and radiological findings

Lipoid proteinosis is a rare inherited genodermatosis characterized by hyaline deposits in various tissues. Clinically, it manifests with cutaneous as well as extracutaneous features. Periodic acid‐Schiff (PAS)‐reactive hyaline deposits in the upper dermis, with localization around blood vessels and eccrine sweat glands, in particular, is the histopathological hallmark finding. On brain imaging, bilateral symmetrical temporal lobe calcifications are considered to be pathognomonic of this disorder. We report a case of lipoid proteinosis in which hyaline deposits were present in the papillary and reticular dermis, without being seen at the periphery of eccrine sweat glands, along with dystrophic calcification. Magnetic resonance imaging (MRI) of brain revealed hydrocephalus, subependymal heterotropia and absent splenium of corpus callosum with no evidence of temporal lobe calcification. Thus, our case highlights the inherent diverse nature of lipoid proteinosis.     

类脂蛋白沉积症1例

报告1例类脂蛋白沉积症，14例男性，头面，四肢，腰部反复发生红斑，水疱，疤痕，伴声音嘶哑12年，组织病理检查可见真皮乳头层血管壁和汗腺周围有透明蛋白样物质沉积，PAS染色强阳性。     

Lipoid proteinosis: Novel ECM1 pathogenic variants and intrafamilial variability in four unrelated Arab families

Background/objectives

Lipoid proteinosis (LP) is a rare autosomal recessive multisystem disorder that is caused by loss-of-function pathogenic variants in the extracellular matrix protein-1 (ECM1) gene. The typical clinical manifestations of LP include hoarseness of voice, beaded papules on the eyelids, infiltration and scarring of the skin and mucosa, as well as neuropsychological abnormalities. Currently, more than 70 pathogenic variants have been reported, including nonsense, missense, splice site, deletion and insertion pathogenic variants, and more than half of them occurred in exons 6 and 7.

Methods

Clinical evaluation and Sanger sequencing were performed on eight patients from four unrelated Arab families.

Results

We identified two novel ECM1 variants, one nonsense pathogenic variant in exon 6 (c.579G>A, p.Trp193*) and a deletion of three nucleotides (c.1390_1392del, p.Glu464del) in exon 9, and two previously reported frameshift variants; c.692_693delAG, in exon 6 and c.11dupC in exon 1.

Conclusions

Although all patients had characteristic manifestations of lipoid proteinosis, we observed intrafamilial phenotypic variability. Our data expand the pathogenic variant spectrum of ECM1 and also supports the fact that exon 6 is one of the most common hot spots of pathological variants in ECM1.     

Lipoid proteinosis: phenotypic heterogeneity in Iranian families with c.507delT mutation in ECM1

Lipoid proteinosis (LP) is a rare autosomal recessive genodermatosis caused by loss‐of‐function mutations in the ECM1 gene, and previous studies have noted phenotypic variability. In this study, we examined 12 patients representing three Iranian families for clinical manifestations and genotyped them for mutations in ECM1. LP was diagnosed with characteristic mucocutaneous and neurologic manifestations. Five patients were also subjected to magnetic resonance imaging (MRI)/computed tomography (CT) scan of the central nervous system. DNA was isolated from peripheral blood from patients and their clinically unaffected relatives, and mutations in ECM1 were sought by PCR‐based amplification of all exons and flanking intronic sequences, followed by bidirectional Sanger sequencing. Significant phenotypic variability in this multisystem disorder, including presence of convulsions and epilepsy in about half of the patients was noted. In most cases, this was associated with calcifications in the brain detected by MRI/CT scans. Genotyping of the affected individuals in three families from the central region of Iran revealed presence of homozygous c.507delT mutation in ECM1, reflecting the observed consanguinity in these families. This large cohort revealed extensive phenotypic variability in individuals with the same mutation in ECM1. This observation suggests a role for genetic and epigenetic as well as environmental modulation of the phenotype. Identification of mutations allows screening of unaffected individuals for presence or absence of this mutation in extended LP families, with implications for genetic counseling.     

冷冻治疗寻常疣3690例临床分析

目的 对寻常疣的病因、冷冻治疗的疗效及并发症进行分析和探讨，以寻求简便高效的治疗方案。方法 应用我科自制的小型液氮冷冻器进行冷冻治疗3690例寻常疣患者，选用喷洒法或接触法冷冻60～150s不等，间隔10min，冻一融2～3个周期。结果 痊愈率97．62％（3602例），其中一次治愈率74．99％（2767例），二次治愈率16.69％（616例），三次治愈率5．93％（219例）；有效率2．38％（88例）；无效率为0。结论 液氮冷冻治疗寻常疣疗效显著，一次治愈率高，副作用小，术后恢复快，值得推广。     

Lipoid proteinosis. A biochemical and ultrastructural investigation of two new cases

Lipoid proteinosis is a rare autosomal recessive disease characterized by cutaneous and visceral lesions, in which large amounts of amorphous material are constantly found in stroma. Morphological and biochemical studies indicate abnormal collagen production, but little attention has been paid to the lipid component of lesions. Microscopic and ultrastructural studies of skin, with special emphasis on fibroblasts, vessels, nerve endings and eccrine sweat glands, were conducted in two patients with lipoid proteinosis. Biochemical studies were undertaken in cultured fibroblasts. Evidence of lysosomal storage in epithelial cells of eccrine sweat glands and in dermal histiocytes, very similar to that found in some metabolic disorders, particularly Farber disease, was found in both cases. Our findings suggest that two alterations might coexist in lipoid proteinosis, one characterized by impaired normal collagen production and the other related to a metabolic defect which may lead to accumulation of ceramide or more complex lipids.     

巨大寻常疣继发原位鳞状细胞癌1例

 报告1例巨大寻常疣继发原位鳞状细胞癌。患者男，54岁，右膝关节斑块10年，破溃结痂2年。皮肤科检查：右膝关节内侧见一范围约5 cm×6 cm角化性斑块，表面乳头状突起，可见厚层痂壳，边界清楚，无破溃、渗出，有臭味，局部轻压痛。皮损组织病理示：表皮角化过度伴角化不全，棘层肥厚，表皮突向下延长，真皮乳头瘤样增生，乳头状突起之间的凹陷处可见明显的颗粒细胞，表皮上部可见挖空细胞；部分表皮全层细胞排列紊乱，大小形态不一，可见异形细胞和角化不良细胞，基底细胞层完整。真皮浅层可见混合炎性细胞浸润。诊断：巨大寻常疣继发原位鳞状细胞癌。予手术完整切除联合植皮治疗，术后半年电话随访，术区恢复良好，无新发皮损。     

Interleukin‐33 is expressed in the lesional epidermis in herpes virus infection but not in verruca vulgaris

Interleukin (IL)‐33 is released on cell injury and activates the immune reaction. IL‐33 is involved in antiviral reaction in herpes virus infection, but the source that secretes IL‐33 has not been identified. We speculate that keratinocytes injured in herpes virus infection secrete IL‐33. In order to detect IL‐33 in the lesional epidermis of patients with herpes virus infection, we immunostained several cutaneous herpes virus infection samples with an anti‐IL‐33 antibody, and compared them with cutaneous human papilloma virus (HPV) infection samples. We observed strong nuclear and mild cytoplasmic staining in epidermal keratinocytes of the lesional skin samples with herpes simplex virus and varicella zoster virus infections. However, staining was not observed in the epidermis of verruca vulgaris (VV) samples. We assumed that the strong immune reaction to herpes virus infection may depend on strong IL‐33 expression in the epidermis, while very weak immune reaction in samples from patients with VV may be due to low or no expression of IL‐33 in the lesional epidermis.     

中国5家系类脂蛋白沉积症临床和遗传特点分析

目的：了解中国人群中类脂蛋白沉积症(LP)的临床表型和遗传学特点。方法：描述了我院确诊的一LP家系中患者的临床表型和遗传特点，并综合20多年来国内文献报道的LP家系进行比较分析。结果：(1)LP在家系中的传递符合常染色体隐性遗传方式；(2)表型特点为患者多在2岁内发病，声音嘶哑、眼睑串珠状半透明丘疹，在每个患者均出现；一些少见的表现，如颅内钙化灶仅在家系1中出现，复发性腮腺炎或扁桃体炎仅在家系1和家系5中出现；6例患者健康状况不受该病影响，家系1中的先证者在18岁时曾出现呼吸困难；(3)多不伴发其他遗传病和系统疾病；(4)患者临床表现有一定程度的相似性，但严重程度有很大差异，既使在同一家系中也如此。结论：LP是一种罕见的常染色体隐性遗传病，中国人群中其致病基因的突变频率很低；LP临床表型相似，但不同患者表现度存在较大差异。     

595nm脉冲染料激光治疗儿童寻常疣的临床疗效评价

目的:评价595 nm脉冲染料激光治疗儿童寻常疣的临床疗效及安全性。方法:将84例患儿分为两组,治疗组(42例)采用595 nm脉冲染料激光治疗,对照组(42例)采用液氮冷冻治疗,每隔2周治疗1次,最多6次。结果:治疗组痊愈率和有效率分别为71.4%和90.5%,高于对照组的40.0%和73.8%,治疗组和对照组平均治愈次数分别是(2.35±0.98)和(3.43±1.21)次,治疗组不良反应发生率(16.7%)明显低于对照组(81.0%),差异均有统计学意义(均P0.05)。结论:595 nm脉冲染料激光治疗儿童寻常疣临床疗效显著优于液氮冷冻。     

类脂质蛋白沉积症两家系调查及ECM1基因突变检测

目的:检测类脂质蛋白沉积症二家系中细胞外基质蛋白(ECM1)基因突变位点。方法:提取1号家系先证者及其母亲,2号家系先证者、父母、配偶及儿子外周血DNA。PCR技术扩增ECM1基因编码序列,采用一代Sanger法对PCR扩增产物进行测序。结果:1号家系先证者在7号外显子发现已知突变(纯合突变c.960GA),其母亲为杂合携带者;2号家系先证者为遗传复合体,是上述突变位点的杂合携带者,此外在3号外显子上存在1个插入突变c.142insC。结论:类脂质蛋白沉积症存在遗传异质性。