Case report: a premature infant with severe intrauterine growth restriction, adrenal insufficiency, and inflammatory diarrhea: a genetically confirmed case of MIRAGE syndrome

Abstract

Introduction: 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.

Case presentation: 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.

Conclusion: 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.

Keywords: MIRAGE syndrome; SAMD9; adrenal insufficiency (AI); enteropathy; hypoplasia.

Figure 1

General appearance at (A) birth, (B) 5 months of postmenstrual age. At birth, there was notable hyperpigmentation, but over time, her skin color improved. She showed normal female genitalia. Perineal skin rashes and ulcerations developed due to chronic diarrhea at 4 months (C).

Figure 2

Pathology of small bowel biopsy at 18 weeks of her age. The small intestinal biopsy (jejunum) shows rather intact mucosal architecture with minimal inflammatory reaction (A). Microvillus inclusions were not found (B).

Figure 3

Renal and adrenal ultrasonography and renal scan. After birth, the parenchymal echogenicity of both the kidneys was increased, showing an undifferentiated corticomedullary junction and tiny cortical cysts. The right kidney was smaller than the left kidney (A). At 20 months of age, there was a small right kidney, but the left kidney growth was relatively preserved, although cortical echogenicity remains increased (B). In the Tc-99m Dimercaptosuccinic acid (DMSA) scan obtained at 6 months, the right kidney uptake is barely visible, indicating nonfunction, while the left kidney function appears unremarkable (C).

Figure 4

Clinical course of enteropathy and correlation of fecal calprotectin level and formula change. * HA, Hydrolyzed formula; BM, Breast milk; PM, Premature milk; Neocate^®, amino acid based fully hydrolyzed formula; NPO, Nil Per Os. The left y axis of the graph is scored from 0 to 2.5 based on the Diapered Infant Stool Scale. The right y axis represents the fecal calprotectin level. The x-axis represents the period after infant birth. Additionally, a graphical representation was created to examine the correlation between calprotectin levels and formula changes.