Fabre Alexandre, Bourgeois Patrice, Chaix Charlène, Bertaux Karine, Goulet Olivier, Badens Catherine
Service de pédiatrie multidisciplinaire, La Timone Children's Hospital, Faculté de médecine, UMR_S910, Aix-Marseille University, Marseille, France
Molecular Genetics, La Timone Children's Hospital, Marseille, France
Trichohepatoenteric syndrome (THES), generally considered to be a neonatal enteropathy, is characterized by intractable diarrhea (seen in almost all affected children), woolly hair (seen in all), intrauterine growth restriction, facial dysmorphism, and short stature. Additional findings include poorly characterized immunodeficiency, recurrent infections, skin abnormalities, and liver disease. Mild intellectual disability (ID) is seen in about 50% of affected individuals. Less common findings include congenital heart defects and platelet anomalies. To date 52 affected individuals have been reported.
DIAGNOSIS/TESTING: The diagnosis of THES is established in a proband with biallelic pathogenic variants in either (formerly ) or (formerly )
To promote maximal weight gain and linear growth, most children initially require parenteral nutrition (PN). As tolerated, oral feeding (typically a semi-elemental diet) can be combined with PN. On the rare occasion that PN is unnecessary, anecdotal reports describe use of mainly an amino acid-based formula. To reduce the burden of infections, immunoglobulins can be supplemented in those with low immunoglobulin levels or immunoglobulin functional abnormalities. Individual management of ID is based on age-appropriate assessments of cognitive development, speech and language development, and psychosocial skills. For children not receiving PN: close monitoring of nutritional status by a pediatric nutritionist to assure prompt intervention as needed. Yearly assessment of: diarrhea for changes that could suggest inflammatory bowel disease; liver function and size; immunoglobulin serum concentration and functionality; TSH level for evidence of hypothyroidism. Periodic assessment of: cognitive development, speech and language, and psychosocial skills for evidence of ID.
THES is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the or pathogenic variants have been identified in an affected family member, carrier testing of at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.
毛发肝肠综合征（THES）通常被认为是一种新生儿肠病，其特征为顽固性腹泻（几乎所有患病儿童均有此症状）、羊毛状头发（所有患者均有）、宫内生长受限、面部畸形和身材矮小。其他表现包括特征不明的免疫缺陷、反复感染、皮肤异常和肝脏疾病。约50%的患病个体有轻度智力障碍（ID）。较少见的表现包括先天性心脏缺陷和血小板异常。迄今为止，已报道52例患病个体。
诊断/检测：在一个先证者中，如果其（以前的）或（以前的）存在双等位基因致病变异，则可确立THES的诊断。
为促进最大程度的体重增加和线性生长，大多数儿童最初需要肠外营养（PN）。在耐受的情况下，口服喂养（通常是半要素饮食）可与PN联合使用。在极少数情况下，如果不需要PN，轶事报道描述主要使用基于氨基酸的配方奶粉。为减轻感染负担，对于免疫球蛋白水平低或免疫球蛋白功能异常的患者，可补充免疫球蛋白。ID的个体管理基于对认知发育、言语和语言发育以及心理社会技能的适龄评估。对于未接受PN的儿童：由儿科营养师密切监测营养状况，以确保根据需要及时进行干预。每年评估：腹泻情况，以发现可能提示炎症性肠病的变化；肝功能和肝脏大小；免疫球蛋白血清浓度和功能；促甲状腺激素水平，以发现甲状腺功能减退的证据。定期评估：认知发育、言语和语言以及心理社会技能，以发现ID的证据。
THES以常染色体隐性方式遗传。在受孕时，患病个体的每个同胞有25%的机会患病，50%的机会为无症状携带者，25%的机会未患病且不是携带者。一旦在患病家庭成员中鉴定出或致病变异，就可以对有风险的亲属进行携带者检测、对风险增加的妊娠进行产前检测以及进行植入前基因检测。
