Persistent lactic acidosis in the Mauriac syndrome in type 1 diabetes mellitus

Abstract

Mauriac syndrome is an uncommon clinical condition arising in the setting of poorly controlled type 1 diabetes mellitus. Clinical features include hepatomegaly and liver abnormalities indistinguishable from nonalcoholic fatty liver disease. Early diagnosis and management are essential, as Mauriac syndrome is reversible.

Mauriac syndrome was first described in 1930. It is a rare complication of poorly controlled type 1 diabetes mellitus characterized by hepatomegaly with altered liver enzymes, growth retardation, delayed puberty, and cushingoid features in prepubertal children.¹ However, it can manifest only with hepatomegaly secondary to glycogen deposition in the liver.² Other findings of Mauriac syndrome include abdominal pain, nausea, vomiting, elevated transaminases, and elevated plasma lactate levels.^3,4 Here, we present a case of a young adult with poorly controlled diabetes presenting with hepatomegaly and persistently lactic acidosis despite resolution of diabetic ketoacidosis.

CASE PRESENTATION

A 21-year-old woman with a history of depression and type 1 diabetes mellitus diagnosed at the age of 2 years presented to the emergency department with nausea, vomiting, diarrhea, decreased appetite, and poor oral intake for 1 day. She had a history of medication noncompliance and repeated intensive care unit admissions for diabetic ketoacidosis. Her home medications included insulin glargine, insulin lispro, trazodone, and venlafaxine.

Examination on presentation revealed dry oral mucous membranes, tachycardia, and diffuse abdominal tenderness. She was afebrile, with a blood pressure of 117/72 mm Hg, a respiratory rate of 19 breaths/min, and a heart rate of 120 beats/min. Her serum glucose was 636 mg/dL; anion gap, 37 mmol/L; beta-hydroxybutyrate, 9.94 mmol/L; and serum bicarbonate, 5 mmol/L. Venous blood gas revealed a pH of 6.86 and partial pressure of carbon dioxide of 13 mm Hg. Serum creatinine was 0.5 mg/dL at baseline. The serum lipase was normal (11 U/L), and alkaline phosphatase was 173 U/L. Her hemoglobin A1C was 14.5% 2 months before presentation.

She was admitted to the medical intensive care unit and treated with intravenous insulin, fluids, and electrolyte replacements as necessary. After 1 day, the acidosis normalized, anion gap closed, and acute kidney injury resolved; the insulin regimen was transitioned from an intravenous to subcutaneous route. Lactic acid was persistently elevated to 7.7 mmol/L despite normalization of the anion gap, bicarbonate, and beta-hydroxybutyrate. Liver biopsy revealed diffuse swelling of hepatocytes with a marked increase in intracytoplasmic glycogen consistent with hepatic glycogenesis. The patient’s abdominal pain was resolved, and there was no lower gastrointestinal bleed. Abdominal ultrasound revealed a liver edge to be 17 cm caudal to the rib cage. On the day of discharge, the patient’s lactic acid was still elevated at 2.4 mmol/L.

DISCUSSION

The pathophysiology of Mauriac syndrome is not completely understood. The liver utilizes GLUT-2 glucose transporter to transport glucose inside the hepatocytes and is not dependent on insulin. In Mauriac syndrome, glucose passes into the hepatocyte during prolonged periods of hyperglycemia, and this transport occurs independently of insulin. Treatment of hyperglycemia with insulin leads to the conversion of the entrapped glucose within the hepatocyte to glycogen. The result is hepatomegaly but with preserved synthetic liver function in most cases.^4,5 The hypercholesterolemia induced by hyperglycemia and ketosis has also been postulated to be another factor causing Mauriac syndrome.⁶ An occult mild glycogen storage disorder has been recently proposed to be a potential causative factor.⁷

Patients with glycogenic hepatopathy can have elevated lactate levels despite having no signs and symptoms of diabetic ketoacidosis or other illnesses.⁸ The actual mechanism of lactic acidosis in these cases is poorly understood.⁹ A proposed mechanism is the shunting of the pathway to lactate formation due to lack of conversion of glucose to pyruvate and reduced gluconeogenesis due to excess insulin during periods of treatment with insulin during diabetic ketoacidosis.¹⁰ Another explanation is that the prolonged state of hyperglycemia leads to primary mitochondrial DNA depletion and cytopathy, leading to glycogenic hepatopathy and lactic acidosis.

Other causes of hepatomegaly need to be ruled out before Mauriac syndrome is diagnosed. These include infectious, autoimmune, and metabolic (primary glycogen storage diseases) etiologies. Nonalcoholic fatty liver disease is more common in patients with diabetes mellitus type 2. A noncontrast CT scan of the abdomen can differentiate between the two; nonalcoholic fatty liver disease would be seen as a hypodense liver while glycogenic hepatopathy would be seen as a hyperdense liver. Nonalcoholic fatty liver disease is associated with hyperinsulinemia and insulin resistance, whereas glycogenic hepatopathy is associated with insulin deficiency.¹¹ The gold standard test for diagnosis of glycogenic hepatopathy is liver biopsy and demonstration of glycogen accumulation in hepatocytes.¹²

As opposed to nonalcoholic fatty liver disease, which can progress to fibrosis and cirrhosis, glycogenic hepatopathy is entirely reversible with good glycemic control.¹³ Liver fibrosis is not typically observed in glycogenic hepatopathy, although there have been reports of macrovesicular and microvesicular steatosis, liver inflammation, and mild fibrosis on liver biopsies in pediatric patients with Mauriac syndrome.⁸ Reversal of glycogenic hepatopathy is reported following pancreatic transplantation in those with diabetes, emphasizing the disease’s reversibility.³ However, it should also be noted that glycogenic hepatopathy can relapse following uncontrolled blood glucose levels if good glycemic control is not achieved.¹⁴