Bilateral cataracts in a 6‐yr‐old with new onset diabetes: a novel presentation of a known INS gene mutation. Issue 7 (4th November 2015)

• Record Type: Journal Article
• Authors: Wasserman, Halley; Hufnagel, Robert B.; Miraldi Utz, Virginia; Zhang, Kejian; Valencia, C. Alexander; Leslie, Nancy D.; Crimmins, Nancy A.
• Is Part Of: Pediatric diabetes. Volume 17:Issue 7(2016)
• Page Start: 535
• Page End: 539
• Publication Date: 2015-11-04
• Subjects: cataract -- exome sequencing -- insulin gene; Diabetes in children -- Periodicals; 616.462
• DOI: 10.1111/pedi.12335
• Languages: English
• ISSNs: 1399-543X

Abstract

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.