RABSON-MENDENHALL SYNDROME

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Rabson-Mendenhall syndrome (RMS) is an uncommon genetic condition marked by several distinctive features. Your body’s ability to harness energy from food and transport it to your cells is fundamental for survival. Imagine it as fueling up your car, except here, sugar acts as the energy source. Typically, a hormone called insulin oversees this process, signaling when sugar should exit the bloodstream and enter cells.

However, in the case of Rabson-Mendenhall syndrome, this mechanism malfunctions. Your body fails to utilize insulin effectively, leading to a rare condition with significant consequences.

This syndrome disrupts not only the process of energy delivery but also influences growth, starting from prenatal stages. Babies born with Rabson-Mendenhall syndrome often exhibit stunted growth and struggle to gain weight, indicating the early impact of this condition.

Rabson-Mendenhall syndrome belongs to a category of disorders known as severe insulin resistance syndromes, which also encompasses conditions like Donohue syndrome and type A insulin resistance syndrome.

Causes

Rabson-Mendenhall syndrome stems from genetic factors inherited from parents, resulting from a flaw in the INSR gene.

In each cell, there are two copies of every gene, inherited from the mother and father, respectively. In Rabson-Mendenhall syndrome, both copies of the INSR gene contain the glitch. If only one copy carries the flaw, the individual won’t develop the syndrome.

Therefore, when a child inherits Rabson-Mendenhall syndrome, it’s because both parents possess one normal and one glitch-containing copy of the INSR gene. Consequently, there’s a 3 in 4 chance that this specific combination won’t occur.

Symptoms of Rabson-Mendenhall syndrome often manifest within the first year of life, varying in severity among individuals.

Head and Face

• Rough skin texture
• Widely spaced eyes
• Deep grooves on the tongue
• Enlarged ears, lips, and jaw

Nails

• Thicker than usual nails

Skin

• Dryness
• Acanthosis nigricans, characterized by darkened and thickened skin, often velvety in texture, particularly in skin folds like the underarms and neck

Teeth

• Larger than normal teeth
• Crowded or premature eruption

Other Signs and Symptoms

• Enlarged organs, including the kidney, heart, penis, and clitoris
• Excessive hair growth
• Slow growth before and after birth
• Abdominal swelling
• Reduced subcutaneous fat
• Weak muscles

Diagnosis

The diagnosis of the Syndrome relies on a blend of clinical observations and laboratory assessments. Initially, individuals undergo screening for symptoms, along with blood sugar level analysis. The primary tests for evaluating insulin resistance include the fasting plasma glucose test (FPG) and the oral glucose tolerance test (GTT). In cases of severe insulin resistance, results typically surpass healthy thresholds (≤99 mg/dL for FPG and ≤139 mg/dL for GTT) by more than 50 units. Additionally, a thorough genetic history is established to assess the risk of recurrence within the family. Given the amalgamation of these findings, an accurate diagnosis is established.

Rabson-Mendenhall syndrome shares commonalities with Donohue syndrome, also known as “Leprechaunism”. Both conditions stem from autosomal recessive disorders triggered by mutations on chromosome 19. Notably, severe insulin resistance and abnormal genital enlargement are among the overlapping symptoms observed in these conditions.

Treatments

Currently, there’s no known cure for Rabson-Mendenhall syndrome. However, managing its specific symptoms can improve the quality of life. For instance, dental abnormalities may be addressed through surgical interventions. The primary treatment objective revolves around maintaining stable blood glucose levels, as insulin is often ineffective even at high doses. Continuous feeding, with carefully planned meals containing complex carbohydrate combinations, proves to be the most effective strategy for blood glucose control. While initially effective, these treatments may lose efficacy over time.

Pharmacological administration of human leptin in high doses has shown promising results in improving fasting hyperglycemia, hyperinsulinemia, basal glucose levels, and glucose and insulin tolerance in Rabson-Mendenhall syndrome patients.

Potential Complications

• Ovarian cysts
• Diabetes, which may lead to ketoacidosis, a life-threatening condition
• Kidney problems

These symptoms collectively contribute to the complexity of the syndrome and its potential impact on various bodily functions.

Prognosis

Unfortunately, Rabson-Mendenhall syndrome severely impacts the quality of life, and the prognosis remains poor due to the absence of a definitive long-term treatment. Life expectancy for affected individuals is typically limited to 1-2 years.

Sources

• Photo credit: Dr. Maad Medical Encyclopedia
• National Institutes of Health, National Center for Advancing Translational Sciences
• National Institutes of Health, National Library of Medicine
• Mayo Clinic
• Cleveland Clinic
• Orpha.net
• National Organization for Rare Disorders
• WebMD