Primary Care Recognition of Rabson-Mendenhall Syndrome Despite Absence of Classical Diabetic Symptoms

Rare disease Background:Rabson-Mendenhall syndrome (RMS) is an extremely rare autosomal recessive disorder caused by pathogenic variants in the insulin receptor gene, leading to severe insulin resistance and compensatory hyperinsulinemia.Classical features include acanthosis nigricans, non-obese or underweight body habitus, hirsutism, dental abnormalities, dysmorphic features, and variable growth abnormalities.Early recognition may be difficult when the initial presentation is dominated by non-specific symptoms rather than classical metabolic complaints. Case Report:A 10-year-old Saudi girl presented to a family medicine clinic with intermittent bilateral leg pain and excessive hunger, without polyuria or polydipsia.Examination revealed extensive acanthosis nigricans, moderate hirsutism, deep voice, high-arched palate, and dental enamel defects.Laboratory evaluation showed severe hyperinsulinemia with insulin level of 3522.5 µU/mL, elevated HbA1c of 8.4% (68 mmol/mol), and biochemical hyperandrogenism.Although RMS is classically associated with growth restriction, the patient was tall for age and had a family history of tall stature, requiring cautious interpretation of growth-related findings.Whole-exome sequencing confirmed a homozygous pathogenic insulin receptor variant (c.433C>T, p.Arg145Cys), establishing the diagnosis of RMS.Treatment included vitamin D supplementation, metformin, basal-bolus insulin therapy, dapagliflozin, home glucose monitoring, diabetes education, dietary counseling, and multidisciplinary followup.Glycemic control remained suboptimal despite treatment intensification, reflecting the severe receptor-level insulin resistance associated with RMS. Conclusions:In this patient, marked acanthosis nigricans, severe hyperinsulinemia, hyperglycemia, and hyperandrogenic features supported evaluation for a genetic insulin resistance syndrome despite the absence of classical diabetic symptoms.