Department of Paediatric Endocrinology, Eskisehir Osmangazi University School of Medicine, Eskisehir, Turkey,
Department of Ophthalmology, Eskisehir Osmangazi University School of Medicine, Eskisehir, Turkey.
Horm Res Paediatr. 2019;91(5):346-355. doi: 10.1159/000495190. Epub 2019 Jan 9.
The term "H syndrome" was coined to denote the major clinical findings, which include hyperpigmentation, hypertrichosis, hearing loss, hepatosplenomegaly, hyperglycaemia, hypogonadism, hallux flexion contractures, and short height.
To report the clinical, endocrinological, histochemical, and genetic findings of three siblings.
Skin and liver biopsies were taken to investigate the histochemical characteristics of hyperpigmented hypertrichotic skin lesions and massive hepatomegaly. The levels of basal serum thyroid hormones, oestradiol, total testosterone, follicle-stimulating hormone, luteinising hormone, and stimulated growth hormone (GH) were measured to investigate the endocrine aspects of the syndrome. Mutation analysis was carried out in all six exons and exon-intron boundaries of SLC29A3 by direct sequencing.
Physical examination of the patients revealed common charac-teristic findings of H syndrome. Additional clinical findings were sectorial iris atrophy in the younger sister. Laboratory evaluation revealed microcytic anaemia, markedly increased erythrocyte sedimentation rate and C-reactive protein levels, and humoral immune deficiency in the younger siblings, who presented with recurrent fever and sinopulmonary infection. Two different GH stimulation tests revealed GH deficiency in the younger sister with short stature. Liver and skin biopsies revealed polyclonal lymphohistiocytic and plasma cell infiltration. Sequencing of SLC29A3 in the three siblings revealed a novel homozygous mutation in exon 6, which caused the transition of arginine to tryptophan.
This study not only extended the clinical and mutation spectrum of SLC29A3 in H syndrome, but also showed that short children should be assessed according to the guidelines for short stature in children.
“H 综合征”一词是用来表示主要的临床发现，包括色素沉着过度、多毛症、听力损失、肝脾肿大、高血糖、性腺功能减退、踇趾屈曲挛缩和身材矮小。
报告三例同胞的临床、内分泌、组织化学和遗传学发现。
取皮肤和肝活检以研究色素沉着过度多毛性皮肤病变和巨大肝肿大的组织化学特征。测量基础血清甲状腺激素、雌二醇、总睾酮、卵泡刺激素、黄体生成素和刺激生长激素（GH）的水平，以研究该综合征的内分泌方面。通过直接测序对 SLC29A3 的所有六个外显子和外显子-内含子边界进行突变分析。
患者的体格检查显示出 H 综合征的共同特征性发现。年轻的妹妹还存在扇形虹膜萎缩的其他临床发现。实验室评估显示年轻的妹妹有小细胞性贫血、红细胞沉降率和 C 反应蛋白水平明显升高，以及体液免疫缺陷，表现为反复发热和肺鼻感染。两项不同的 GH 刺激试验显示身材矮小的妹妹存在 GH 缺乏症。肝和皮肤活检显示多克隆淋巴组织细胞和浆细胞浸润。对三兄妹的 SLC29A3 测序发现了一个新的外显子 6 中的纯合突变，导致精氨酸突变为色氨酸。
本研究不仅扩展了 SLC29A3 在 H 综合征中的临床和突变谱，还表明矮小的儿童应根据儿童矮小症的指南进行评估。
