Title: Bilateral cataracts in a 6-yr-old with new onset diabetes: a novel presentation of a known INS gene mutation.
Authors: Wasserman, Halley; Hufnagel, Robert B; Miraldi Utz, Virginia; Zhang, Kejian; Valencia, C Alexander; Leslie, Nancy D; Crimmins, Nancy A
Published In Pediatr Diabetes, (2016 11)
Abstract: The prevalence of diabetes-related cataracts during childhood is less than 1%. When cataracts occur, it is often in adolescent females with prolonged symptoms and significant hyperglycemia. Cataracts are not a classic feature of monogenic diabetes. We report a case of a 6-yr-old, previously healthy Caucasian male, who presented with bilateral acquired cataracts and was subsequently diagnosed with new onset diabetes. Additional symptoms at presentation included a several year history of polyuria and polydipsia, mild hepatomegaly, and short stature. Pertinent negatives include acanthosis nigricans, lipoatrophy, deafness, muscle weakness, or neuropathy. HbA1c was significantly elevated at diagnosis (>14%, 129.5 mmol/mol) without evidence of ketosis. Autoantibody testing was negative. Features of Mauriac syndrome (short stature, hepatomegaly) as well as acquired cataracts indicated long-standing hyperglycemia with sufficient insulin production to prevent ketone production and development of diabetic ketoacidosis. Whole exome sequencing was conducted and a de novo heterozygous mutation in the INS gene (c.94G>A; p.Gly32Ser) was identified. INS gene mutations are common causes of permanent neonatal diabetes but rare causes of antibody-negative diabetes in children. Importantly, INS gene mutations have not been previously associated with acquired cataracts. Knowledge of a monogenic cause of diabetes allows clinicians to tailor counseling and screening of diabetes-related comorbidities. In summary, this case highlights the need to consider testing for monogenic diabetes, specifically INS gene mutations, in pediatric patients with antibody-negative diabetes, especially if complications of prolonged hyperglycemia are present at diagnosis.
PubMed ID: 26530398
MeSH Terms: Cataract/blood; Cataract/etiology*; Cataract/genetics; Child; Diabetes Complications/blood; Diabetes Complications/diagnosis; Diabetes Complications/genetics*; Diabetes Mellitus/blood; Diabetes Mellitus/diagnosis; Diabetes Mellitus/genetics*; Diagnosis, Differential; Humans; Hyperglycemia/blood; Hyperglycemia/complications; Hyperglycemia/genetics; Insulin/genetics*; Male; Mutation, Missense*