Case Report: Diabetes Mellitus as a Novel Endocrine Manifestation of Alpha Thalassemia X-Linked Intellectual Disability (ATR-X) Syndrome
Year: 2026
Type: article
Study design: Case Report
Abstract: Background: Alpha thalassemia/mental retardation X-linked (ATR-X) syndrome is a rare congenital disorder caused by mutations in the ATRX gene, predominantly affecting males and characterized by a broad spectrum of clinical features including intellectual disability, distinctive craniofacial/skeletal anomalies, urogenital malformations, and alpha thalassemia. Currently, dysglycemia and fulminant diabetes mellitus are not recognized as an endocrine-associated comorbidity of ATR-X syndrome. Case Report: This case report presents a 14-year-old male with ATR-X syndrome who presented with hypoactivity, increased secretion burden, and 3 days of fever admitted for evaluation and eventual management of recurrent pseudomonal tracheitis with intravenous (IV) antibiotics. Initial evaluation incidentally revealed marked hyperglycemia with a fasting plasma glucose of 320 mg/dL, prompting further evaluation that showed an elevated hemoglobin A1c (HbA1c) of 10.2% and mild ketosis without acidosis, consistent with diabetes mellitus. Type 1 diabetes-associated antibodies were ultimately negative, and his presentation was not consistent with other more common forms of diabetes, such as type 2 diabetes. As per relatives, the patient had polyuria, polydipsia, and unintentional weight loss of 15 pounds in the prior month. Family history was significant for a 20-year-old brother also with ATR-X syndrome who was diagnosed at 16 years of age with insulin-dependent diabetes of unknown etiology. The patient started basal-bolus insulin with adjustments based on glycemic trends as per continuous glucose monitoring (CGM) with improvements in his glucose levels throughout admission. He was discharged home on this regimen and a CGM. Conclusions: While not previously described in humans, murine models have demonstrated structural and inflammatory changes, associating ATRX deficiency with glucose dysregulation. Pancreatic histopathological findings include interlobular edema, ductal dilation, loss of lobular organization, ductal dysplasia, perivascular/peripancreatic/islet/acinar inflammation, hyperplasia of the islet cells, and fatty infiltration. These pancreatic findings in ATRX -deficient mice provide a plausible mechanism for the impaired glucose tolerance, dysregulated insulin secretion, and β-cell dysfunction seen in this case. In the end, this case suggests a possible mechanism between ATR-X syndrome and clinical diabetes not previously reported in humans. This report highlights the importance of consideration of and monitoring for diabetes mellitus in patients with ATR-X syndrome as a direct consequence of the syndrome itself.
Source: Current Genetic Medicine Reports
Institution: University of California, Los Angeles
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7170639121