Characteristic phenotypes of ADH5/ALDH2 deficiency during childhood.

ADH5/ALDH2 deficiency is a rare inherited syndrome characterized by short stature, microcephaly, delayed mental development, and hematopoietic dysfunction and has recently been proposed as a disease paradigm. Acute and severe presentations include aplastic anemia, myelodysplastic syndrome, or leukemia, requiring bone marrow transplantation during childhood. Conversely, non-hematological manifestations may exhibit a prolonged and nonspecific clinical trajectory, with growth failure and developmental delay, most of which are often overlooked, particularly in patients with milder symptoms. Here, we describe the clinical course of a girl with a wide spectrum of clinical presentations, including nonspecific hematopoietic disorders, growth retardation, mild developmental delay, amblyopia, hemophagocytic lymphohistiocytosis, and verruca vulgaris, culminating in a genetic diagnosis of AMeD syndrome at 12 years of age. We also summarized the clinical manifestations of previously reported cases of AMeD syndrome. Cumulatively, 13 females and 5 males have been documented, with a cardinal triad of symptoms, aplastic anemia, short stature, and intellectual disability. Additional characteristic observations included pigmentary deposition in approximately half of the cases and skeletal difficulties in one-quarter. We propose that early diagnosis of patients who exhibit relatively mild phenotypes of skin or skeletal lesions is important for managing and improving the quality of life of patients with AMeD syndrome.

Central hypoadrenocorticism associated with Rathke's cleft cyst.

Rathke's cleft cysts (RCCs) are non-neoplastic, sellar or suprasellar epithelium-lined cysts originating from Rathke's pouch in the pituitary gland. Patients with RCCs are usually asymptomatic, but some have only been identified when symptoms manifested in middle age. The characteristics of these patients during childhood or adolescence remains unknown. We describe an 18-year-old girl who had occasionally suffered from malicious fatigue in the morning since her early teens. Brain magnetic resonance imaging (MRI) revealed T1 hyperintense/T2 hypointense signals between the anterior and posterior pituitary glands, indicating the presence of RCC. Based on an authentic endocrinological evaluation, her adrenal function seemed normal; nevertheless, her serum cortisol level strangely dropped around noon. Furthermore, daily supplementation of oral hydrocortisone bizarrely suppressed ACTH secretion to below the detection range in the morning. These data appeared compatible with the presence of central adrenal dysfunction. We also review the literature for previously reported cases. In conclusion, the symptoms and endocrinological data for dysfunction of the hypothalamic pituitary system might be non-specific and vary among patients, especially in teenagers. Brain MRI and daily cortisol profiling in blood are key to obtaining a diagnosis of an impaired hypothalamic adrenal function due to RCC.