Introduction
Mauriac syndrome is a metabolic complication caused by poor glycemic control for several years. The condition is more prevalent in children, characterized by growth failure and delayed puberty. The condition was common before introducing long-acting insulin for treating type 1 diabetes or using HbA1c (Hemoglobin A1c, a test to measure glucose attached to hemoglobin) for glycemic control monitoring. It has become less common after the advancement in diabetes treatment with the introduction of newer insulin regimens or analogs.
What Is Mauriac Syndrome?
It is a rare complication of poorly controlled type 1 diabetes mellitus. The condition is also termed glycogen hepatopathy. This medical condition was first described in 1930 by Pierre Mauriac. The individuals affected by this syndrome have severe growth failure, maturational delay, hepatomegaly (liver enlargement), and abdominal distention. Retinopathy and nephropathy are frequently associated with Mauriac syndrome. The condition has equal prevalence among males and females and is more prevalent among adolescents. Two types of Mauriac syndrome are described depending on the presence or absence of obesity. In the obese type, poor glycemic control is caused by fluctuations between hyper and hypoglycemia. In the non-obese type, inadequate insulin administration, lack of ketoacidosis, and lack of alternating hypoglycemia occur.
When first discovered, glycogen hepatopathy was considered a part of Cushing syndrome due to similar clinical presentation. However, later it was discovered that glycogen hepatopathy could occur in the absence of Mauriac syndrome in adult patients with poorly controlled type 1 diabetes Mellitus. The condition is described as transient liver dysfunction with elevated liver enzymes and liver enlargement caused by glycogen deposition. The hepatic features are similar to Mauriac syndrome, but the extrahepatic features are absent.
What Is the Cause of Mauriac Syndrome?
Even though high blood sugar levels are common among type I diabetics, the Mauriac syndrome occurrence is rare. Studies on patients with severe Mauriac syndrome have shown mutations in PHKG2 (phosphorylase kinase gamma catalytic chain), a catalytic sub enzyme of glycogen phosphorylase kinase. The enzyme is a large complex that is responsible for the activation of glycogen phosphorylase, which is the first enzyme in glycogen metabolism. The mutation causes abnormal deposition of glycogen in the liver. Therefore, it can be concluded that a mutant enzyme and a high blood glucose level are necessary for Mauriac syndrome development.
Other studies have suggested a combination of factors is responsible for Mauriac syndrome development. The factors include inadequate glucose utilization by tissues, reduction in insulin-like growth factor-1 (IGF-1), growth hormone levels, and resistant or defective hormone receptors.
What Is Type 1 Diabetes?
Type 1 diabetes is an insulin-dependent chronic condition that develops in young children or adolescents. The condition is caused by the absence or less insulin produced by the pancreas. Genetic or viral diseases may cause the development of type 1 diabetes. The condition is not curable but can be effectively managed with insulin administration or dietary and lifestyle changes.
What Are the Symptoms of Mauriac Syndrome?
The symptoms of Mauriac syndrome include
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Obesity
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Hepatomegaly
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Cushingoid appearance.
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Elevated liver enzymes.
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Growth failure or dwarfism.
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Delayed puberty.
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Protuberant belly.
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Delays in development and sexual maturity.
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Hypertension development is secondary to diabetic nephropathy.
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Hypercholesterolemia (high cholesterol level in blood)
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Visual disturbance.
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Nausea, vomiting, and abdominal pain.
What Is the Pathophysiology of Mauriac Syndrome?
Hepatomegaly develops due to the deposition of glycogen in the liver. Wide fluctuations of periods with hyperglycemia and hyperinsulinism are necessary for glycogen deposition in the liver. Hyperglycemia causes the flow of excess glucose into hepatocytes. Hyperinsulinemia stimulates glycogen synthase for the conversion of glucose-6-phosphate to glycogen. Deposition of glycogen subcutaneously gives rise to a round and moon-like face. The condition is frequent in poorly controlled diabetes when only short-acting insulin is used. A catabolic state is formed when insufficient tissue glucose leads to gluconeogenesis (glucose formation from the non-carbohydrate substrate) and fat metabolism. Short stature is caused by reduced somatomedin (a protein that promotes cell growth) production. High cortisol levels are one of the findings. However, the pituitary-adrenal axis remains intact.
How to Diagnose Mauriac Syndrome?
The condition must be suspected in individuals with poorly controlled type 1 diabetes and cushingoid face. Regular glucose monitoring is essential. Patients with Mauriac syndrome exhibit hyperglycemia. Laboratory tests must be performed to diagnose alkaline phosphatase levels that appear elevated in the syndrome. Elevation of hemoglobin A1C is suggestive of poor glycemic control. Radiographic imaging of the liver with computed tomography reveals hyperdensity due to glycogen deposition. The presence of glycogen in the liver is confirmed with a biopsy and is a mandatory test for disease diagnosis.
What Is the Differential Diagnosis for Mauriac Syndrome?
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Alcoholic Fatty Liver Disease: The condition develops due to heavy consumption of alcohol. When alcohol is broken down in the liver, harmful substances released can damage and inflammation and weaken the body's natural defense system. The condition is more prevalent in individuals with type 2 diabetes.
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Non-alcoholic Steatohepatitis: It is a condition in which fat builds up in the liver. The accumulated fat causes damage and inflammation of liver cells. Most individuals are asymptomatic, while some patients may have reduced liver function. The disorder is more prevalent among type 2 diabetics. Mauriac syndrome is often misdiagnosed with this disease. However, cirrhosis and fibrosis of the liver developing in non-alcoholic steatohepatitis are absent in Mauriac syndrome.
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Autoimmune Hepatitis: It is a condition in which liver inflammation develops due to the body's immune cells attacking normal liver cells. If left untreated, the disease progresses to form liver cirrhosis (scarring of the liver), ultimately resulting in liver failure.
How to Treat Mauriac Syndrome?
The symptoms of Mauriac syndrome are improved with better blood sugar control and following diet recommendations. The treatment used earlier was multiple insulin injection therapy. However, rapid reduction of blood sugar levels can cause retinopathy. Therefore, continuous insulin delivery is recommended to reduce blood sugar levels gradually. Studies are ongoing on the effectiveness of insulin pump therapy for treating Mauriac syndrome. Children with therapy for Mauriac syndrome have a good prognosis and fast resolution of symptoms after achieving glycemic control. However, there is a chance for relapse, but the condition does not progress into end-stage liver disease.
Conclusion
Mauriac syndrome is a rare complication of poor glycemic control in type 1 diabetes patients. The treating doctor must have a high degree of suspicion for diagnosing and treating the condition at the earliest. Reasonable glycemic control can reverse most of the hepatic symptoms. The extrahepatic symptoms of developmental delay and delay in sexual maturity require early treatment.
