Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Front Endocrinol (Lausanne). 2023 Sep 6;14:1242387. doi: 10.3389/fendo.2023.1242387. eCollection 2023.
MIRAGE syndrome is a rare disease characterized by myelodysplasia, infection, growth restriction, adrenal hypoplasia, genital phenotypes, and enteropathy. Herein, we report the case of a girl with MIRAGE syndrome who presented with adrenal insufficiency and chronic diarrhea.
The patient was born at 29 + 6 weeks of gestational age with a birth weight of 656 g (<3p). Her height and head circumference were also <3p. At birth, she presented with respiratory distress, meconium staining, and pneumomediastinum, which were managed with high-frequency ventilation and empirical antibiotics. Physical examination showed generalized hyperpigmentation and normal female genitalia. A few days after birth, polyuria and hypotension developed, and laboratory findings revealed hypoglycemia, hyponatremia, and hyperkalemia. Plasma adrenocorticotropic hormone levels were elevated with low serum cortisol levels and high plasma renin activity, which were suggestive of adrenal insufficiency. Hydrocortisone and fludrocortisone were introduced and maintained, and hyperpigmentation attenuated with time. Both kidneys looked dysplastic, and adrenal glands could not be traced on abdominal ultrasound. From the early days of life, thrombocytopenia and anemia were detected, but not to life-threatening level and slowly recovered up to the normal range. Despite aggressive nutritional support, weight gain and growth spurt were severely retarded during the hospital stay. Additionally, after introducing enteral feeding, she experienced severe diarrhea and subsequent perineal skin rashes and ulcerations. Fecal calprotectin level was highly elevated; however, a small bowel biopsy resulted in non-specific submucosal congestion. The patient was diagnosed with MIRAGE syndrome with SAMD9 gene mutation. She was discharged with tube feeding and elemental formula feeding continued, but chronic diarrhea persisted. By the time of the last follow-up at 15 months of corrected age, she was fortunately not subjected to severe invasive infection and myelodysplastic syndrome. However, she was dependent on tube feeding and demonstrated a severe developmental delay equivalent to approximately 5-6 months of age.
The early diagnosis of adrenal crisis and hormone replacement therapy can save the life of -patients with MIRAGE syndrome; however, chronic intractable diarrhea and growth and developmental delay continue to impede the patient's well-being.
MIRAGE 综合征是一种罕见疾病，其特征为骨髓增生异常、感染、生长受限、肾上腺发育不全、生殖器表型和肠病。本文报告了一例 MIRAGE 综合征患儿，其表现为肾上腺功能不全和慢性腹泻。
患儿胎龄 29+6 周，出生体重 656g（<3 百分位），身高和头围也<3 百分位。出生时，患儿有呼吸窘迫、胎粪污染和纵隔气肿，接受高频通气和经验性抗生素治疗。体格检查显示全身色素沉着过度和正常女性生殖器。出生后数天，患儿出现多尿和低血压，实验室检查发现低血糖、低钠血症和高钾血症。血浆促肾上腺皮质激素水平升高，血清皮质醇水平低，血浆肾素活性高，提示肾上腺功能不全。给予氢化可的松和氟氢可的松，随着时间的推移，色素沉着逐渐减轻。双肾外观发育不良，腹部超声未追踪到肾上腺。从生命早期开始，血小板减少和贫血，但未达到危及生命的程度，随着时间的推移逐渐恢复到正常范围。尽管进行了积极的营养支持，但住院期间体重增加和生长突增严重延迟。此外，开始肠内喂养后，患儿出现严重腹泻，随后出现肛周皮肤皮疹和溃疡。粪便钙卫蛋白水平显著升高；然而，小肠活检结果为非特异性黏膜下充血。患儿被诊断为 MIRAGE 综合征，存在 SAMD9 基因突变。她出院时仍接受管饲和要素配方喂养，但慢性腹泻持续存在。在 15 个月的校正年龄时进行最后一次随访时，患儿幸运地未发生严重侵袭性感染和骨髓增生异常综合征。然而，她仍依赖于管饲喂养，表现出严重的发育迟缓，相当于大约 5-6 个月的年龄。
早期诊断肾上腺危象并进行激素替代治疗可以挽救 MIRAGE 综合征患儿的生命；然而，慢性难治性腹泻和生长发育迟缓仍然影响患儿的健康。
