title: Bilateral cataracts in a 6-yr-old with new onset diabetes: a novel presentation of a known INS gene mutation.
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.
authors.affiliation: Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. halley.wasserman@cchmc.org.
authors.forename: Halley
authors.initials: H
authors.lastname: Wasserman
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Hufnagel
authors.affiliation: Department of Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Miraldi Utz
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Kejian
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: C Alexander
authors.initials: CA
authors.lastname: Valencia
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Leslie
authors.affiliation: Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Crimmins
mesh_terms: D002386:Cataract / Q000097:blood / Q000209:etiology* / Q000235:genetics; D002648:Child; D048909:Diabetes Complications / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D003920:Diabetes Mellitus / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D003937:Diagnosis, Differential; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000150:complications / Q000235:genetics; D007328:Insulin / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense
chemical_list: D007328:Insulin
keywords: cataract; exome sequencing; insulin gene