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Health condition

Donohue and Rabson-Mendenhall awareness

Donohue syndrome and Rabson-Mendenhall syndrome are the severest forms of inherited insulin receptor deficiency, presenting in infancy and childhood; awareness matters for carrier parents, milder spectrum cases reaching adulthood, and families seeking genetic counselling.

Why trust this guide

  • 01

    Editorial team

    Written by our editorial team from the UK sources listed on each page.

  • 02

    Sourced from guidance

    Checked against current NHS and UK specialist society guidance at the time of review.

  • 03

    Current for 2026

    Reviewed on 2026-09-27 with the next review scheduled for 2027-09-27.

Key facts

The essentials at a glance.

The symptoms to recognise, when to seek help, which specialist to see, and what treatment usually involves.

  • Both are recessive insulin receptor (INSR) gene disorders - two faulty copies inherited, one from each parent

  • Donohue syndrome is the most severe, presenting in infancy; Rabson-Mendenhall is intermediate, with survival into adolescence and adulthood

  • Features across the spectrum: extreme insulin resistance, growth impairment, characteristic facial features, acanthosis nigricans, and dental and nail abnormalities

  • Milder INSR spectrum disease (type A insulin resistance) can present in adolescence or adulthood, especially in women with severe PCOS-like features

  • Specialist centres offer trials of recombinant IGF-1 therapy; genetic counselling is essential for affected families and carrier couples

Understanding the condition

What it is and what happens next.

What causes it, how it is diagnosed, and the treatment routes available in the UK.

What it is and how it feels

The insulin receptor is the single gateway for insulin's message, and near-total loss is barely survivable: infants with Donohue syndrome show profound growth failure and metabolic chaos. Rabson-Mendenhall sits between that and the milder type A resistance - children and young adults with extraordinary insulin levels, disturbed growth and teeth, and glucose that swings between highs and paradoxical fasting lows. For adult medicine the syndrome matters at its edges: carrier parents planning further children, and milder biallelic or heterozygous cases who reached adulthood underdiagnosed.

Diagnosis and treatment routes

Genetic confirmation anchors everything - prognosis, treatment trials and reproductive options including prenatal and preimplantation testing for carrier couples. Management belongs in national severe insulin resistance centres, where high-dose insulin strategies, metformin and recombinant IGF-1 are deployed and families connected to research. A family history of these syndromes, or an unexplained extreme insulin resistance picture, warrants specialist genetic and endocrine review; private initial appointments are typically available within about two weeks.

Seeing a specialist

Who to see, and how quickly you can be seen.

The specialist for this condition is usually a consultant endocrinologist (specialist centre). Your GP can refer you on the NHS, or you can arrange a private consultation directly.

A quiet reminder

This guide is for information, not medical advice.

Your GP knows your history and can tell you which parts apply to you. If in doubt, see them - and seek urgent care for any of the emergency symptoms described above.

Frequently asked

Common questions about Donohue and Rabson-Mendenhall awareness.

Quick, plain-English answers to what people ask us most.

  • What are Donohue and Rabson-Mendenhall syndromes?

    Donohue syndrome and Rabson-Mendenhall syndrome are the two most severe forms of inherited insulin receptor deficiency, causing profound insulin resistance and characteristic physical features, typically presenting very early in life.

  • What causes these syndromes?

    Both are caused by inherited mutations affecting the insulin receptor, meaning the body's cells can't respond properly to insulin despite the hormone often being present at very high levels, leading to severe insulin resistance.

  • What are the symptoms of these conditions?

    Features include severe growth abnormalities, characteristic facial features, skin changes (such as acanthosis nigricans - dark, thickened skin), and severe metabolic problems related to profound insulin resistance.

  • Are Donohue and Rabson-Mendenhall syndromes dangerous?

    Yes, Donohue syndrome in particular is extremely severe, often associated with very limited life expectancy in infancy, while Rabson-Mendenhall syndrome, though also serious, can have a somewhat longer, though still significantly shortened, life expectancy.

  • Are these syndromes hereditary?

    Yes, both are inherited in an autosomal recessive pattern, meaning both parents carry a faulty gene copy. Genetic counselling is important for affected families given the severity of these conditions.

  • How are these conditions treated?

    Management focuses on trying to control severe metabolic abnormalities, sometimes with very high-dose insulin or other specific treatments aimed at improving insulin signalling, though treatment options remain limited given the severity of the underlying receptor defect.

  • Can Donohue or Rabson-Mendenhall syndrome be cured?

    There's no cure currently for the underlying genetic receptor defect; care focuses on supportive management and trying to optimise metabolic control as much as possible given the severity of the condition.

  • How are these conditions diagnosed?

    Diagnosis typically involves recognising the characteristic clinical features alongside genetic testing to confirm mutations in the insulin receptor gene, usually undertaken by a specialist paediatric endocrinology and genetics team given the rarity.

  • Donohue syndrome vs Rabson-Mendenhall syndrome - how do they differ?

    Both result from severe insulin receptor dysfunction, but they differ somewhat in specific features and typical severity, with Donohue syndrome generally considered the more severe of the two, though both are extremely rare and serious.

  • When should I seek specialist assessment for a suspected diagnosis?

    Seek assessment from a specialist paediatric endocrine genetics centre as early as possible if these conditions are suspected in an infant, given the severity and need for prompt, specialised metabolic management.