Belli Gilda, Bartolini Emanuele, Bianchi Andrea, Mascalchi Mario, Stagi Stefano
Department of Health Sciences, University of Florence, Anna Meyer Children's University Hospital, Florence, Italy.
Neurology Unit and Laboratories, Anna Meyer Children's University Hospital, Florence, Italy.
Front Endocrinol (Lausanne). 2018 Aug 24;9:497. doi: 10.3389/fendo.2018.00497. eCollection 2018.
Metachromatic leucodystrophy (MLD) is a rare inherited lysosomal disorder caused by reduced activity of the enzyme arylsulfatase A with accumulation of sulfatides in the nervous system. We report a female child affected by MLD who developed central precocious puberty (CPP). This association has not been described so far. The proposita, after normal growth and psychomotor development, at age of 30 months presented with a rapidly progressive gait disturbance with frequent falls and with loss of acquired language skills. Magnetic resonance imaging showed leukoencephalopathy. Biochemical blood essays showed a 91% reduction in the arylsulfatase A activity and genetic analysis revealed compound heterozygous mutations of the gene, enabling diagnosis of MLD. Subsequently, the patient had further rapid deterioration of motor and cognitive functions and developed drug-resistant epilepsy. At 4 years and 7 months of age bilateral thelarche occurred. Magnetic resonance imaging showed a small pituitary gland, extensive signal changes of the brain white matter, increased choline, decreased N-acetyl-aspartate and presence of lactate on HMR spectroscopy. Pelvic ultrasound demonstrated a slightly augmented uterine longitudinal diameter (42 mm). The gonadotropin-releasing hormone stimulation test revealed a pubertal LH peak of 12.9 UI/l. A diagnosis of CPP was made and treatment with gonadotropin-releasing hormone agonists was initiated, with good response. In conclusion, a CPP may occur in MLD as in other metabolic diseases with white matter involvement. We hypothesize that brain accumulation of sulfatides could have interfered with the complex network regulating with the hypothalamic-pituitary axis and thus triggering CPP in our patient.
异染性脑白质营养不良（MLD）是一种罕见的遗传性溶酶体疾病，由芳基硫酸酯酶A活性降低导致硫脂在神经系统中蓄积引起。我们报告了一名患有MLD的女童，她出现了中枢性性早熟（CPP）。这种关联迄今尚未见报道。该先证者在正常生长和精神运动发育后，30个月大时出现快速进展的步态障碍，频繁跌倒，并丧失了已习得的语言技能。磁共振成像显示脑白质病。血液生化检查显示芳基硫酸酯酶A活性降低了91%，基因分析揭示了该基因的复合杂合突变，从而确诊为MLD。随后，患者的运动和认知功能进一步快速恶化，并出现耐药性癫痫。4岁7个月时双侧乳房发育。磁共振成像显示垂体较小，脑白质广泛信号改变，胆碱增加，N-乙酰天门冬氨酸减少，磁共振波谱显示有乳酸存在。盆腔超声显示子宫纵径略有增加（42mm）。促性腺激素释放激素刺激试验显示青春期促黄体生成素峰值为12.9UI/l。诊断为CPP并开始用促性腺激素释放激素激动剂治疗，反应良好。总之，MLD可能如其他累及白质的代谢性疾病一样发生CPP。我们推测硫脂在脑内的蓄积可能干扰了调节下丘脑-垂体轴的复杂网络，从而引发了我们患者的CPP。
