Department of Pediatric Gastroenterology, Primary Children's Hospital, University of Utah School of Medicine, Salt Lake City, UT 84113-1103, USA
Copyright © 2009 John F. Pohl. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
A 17-year-old male with type 1 diabetes mellitus (T1DM) presented to clinic with elevated transaminases and a positive antinuclear antibody (ANA) screen. Due to concern for autoimmune hepatitis, a liver biopsy was performed which revealed Mauriac syndrome. This case report is the second known description of a child with Mauriac syndrome presenting with positive autoimmune markers.
Mauriac syndrome is associated with poor control of T1DM and presents as hepatomegaly and elevated transaminases . It is typically associated with growth failure and delayed pubertal maturation, although these effects can be reversed with good glycemic control .
2. Case Report
A 17-year-old male was referred to the pediatric gastroenterology clinic due to elevated transaminases noted during standard screening blood work. The patient had a history of type I diabetes mellitus (T1DM) diagnosed since 5 years of age with the patient having multiple hospital admissions for diabetic ketoacidosis secondary to noncompliance with insulin therapy. Past medical history was significant for pyloric stenosis repair at 4 weeks of age and a prior history of tonsillectomy and adenoidectomy. Family history was noncontributory. His current medication consisted of Humalog Mix 75/25 insulin (Eli Lilly and Company) with the patient receiving approximately 1.3 units of insulin per kilogram body weight.
The patient had no history of jaundice or scleral icterus, and he denied right upper quadrant pain, pruritis, weight loss, ascites, hematemesis, or rectal bleeding. A review of his blood glucose monitoring demonstrated a range of 250–310 milligram per deciliter (mg/dL), and he had a hemoglobin A1c of 12.3% suggesting poor glycemic control.
A liver ultrasound showed normal hepatic echotexture and minimal sludge in the gallbladder (Figure 1). A complete blood count, prothrombin time, activated partial thromboplastin time, lipid panel, free thyroxine level, and tissue transglutaminase serum IgA level were normal. However, transaminases were elevated with an aspartate aminotransferase (AST) and alanine aminotransferase (ALT) consisting of 63 international units per liter (IU/L) and 209 IU/L, respectively. Direct bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase levels were normal. A viral hepatitis panel, serum ceruloplasmin, and alpha 1-antitrypsin phenotype were normal. The patient was noted to have an elevated ANA titer ( in a homogenous pattern). Screening for smooth muscle antibody was negative, and it was decided that a percutaneous liver biopsy should be performed due to the possibility of type 1 autoimmune hepatitis.
A subsequent liver biopsy demonstrated normal portal tracts (H&E 100, Figure 2(a)); however, hepatocytes demonstrated cytoplasmic clearing secondary to increased intracellular glycogen and microvesicular fat (H&E 200, Figure 2(b)). This biopsy was consistent with Mauriac syndrome and the importance of improved adherence to insulin therapy was expressed to the patient and his family.
Mauriac syndrome, first described in 1947, is a rare complication associated with T1DM and is typically associated with poor insulin compliance and glycemic control . Although hepatomegaly and elevated serum transaminases are common findings in Mauriac syndrome, other described pediatric manifestations can include malnutrition, growth failure, and development of cushingoid features [1, 2]. Malnutrition associated with poor T1DM control also can lead to false elevation of the sweat chloride concentration, so such patients can present with false-positive screens for cystic fibrosis .
T1DM is associated with other autoimmune diseases, including celiac disease and autoimmune thyroiditis, and it is common for patients with T1DM to have elevated autoantibody titers . Only one prior case report has described Mauriac syndrome in the setting of positive autoantibodies. In this case, a 16-year-old male with poorly controlled T1DM presented with elevated serum transaminases and a positive ANA of . A subsequent liver biopsy was consistent with Mauriac syndrome .
Typically, a liver biopsy in the setting of Mauriac syndrome will demonstrate steatosis as well as glycogen deposition although such findings can vary in presentation [6, 7]. Poor T1DM control leads to fatty acid transport to the liver, due to hyperglycemia and low insulin levels, which causes hepatomegaly and characteristic liver biopsy findings. These findings reverse with improved insulin control .
Mauriac syndrome is a rare complication of T1DM. Liver biopsy may be warranted in any patient with T1DM and positive autoimmune markers in order to rule out autoimmune hepatitis. Further studies are needed to help delineate patients with Mauriac syndrome from those patients with autoimmune hepatitis.
The author has done consultative work for Eurand Pharmaceuticals, Inc. and PeerPoint Medical Education Institute.
Mauriac syndrome is characterized by dwarfism, obesity and hepatomegaly in patients with insulin-dependent diabetes mellitus. It is associated with poor control of type 1 diabetes mellitus (T1DM) in adolescents, and may present as obesity, hepatomegaly, cushingoid facies and elevated transaminases. It is typically associated with growth failure and delayed pubertal maturation, which should alert the physician over insufficient management of diabetes mellitus and the related development of Mauriac syndrome, although these can be reversed with good glycemic control.
A 21-year-old male with a 10 year history of T1DM was admitted for evaluation of growth retardation, abdominal distension and diabetes. The patient was on pre-mixed insulin (30/70) - 0.8 unit/kg of body weight per day in two divided doses of 15 units and 10 units. He had poor control of diabetes with no regular follow-ups. There was no history of diabetic ketoacidosis, but multiple episodes of documented hypoglycemia were reported. There was no history of hypertension or family history of diabetes. Anthropometric data revealed height 137 cm (<3rd percentile), weight 33 kg (<3rd percentile), body mass index 17.58 kg/m2, height age 10.5 years, weight age 11 years, bone age 7.3 years, upper segment 69 cm, lower segment 68 cm and arm span 136 cm [Figure 1].
Child of type 1 diabetes and Mauriac syndrome
His intelligent quotient was 96 and his mental age was 14 years. Physical examination revealed hypertension (BP 170/120 mmHg on repeated recordings), moon facies, thin scalp hair, cold skin, high pitched voice, protuberant abdomen and hepatomegaly. The patient was prepubertal with tanner stage 1 for testicular and pubic hair development. There was no vitiligo or widely spaced nipples. Fundus examination revealed bilateral severe proliferative diabetic retinopathy with macular edema and grade 2 hypertensive retinopathy. Laboratory analysis revealed: Hemoglobin 11.6 g/dl, total protein 6.4 g/dl, albumin 3 g/dl, triglycerides 145 mg/dl, total cholesterol 261 mg/dl, High density Lipoprotein-cholesterol 42 mg/dl and Low density Lipoprotein-cholesterol 190 mg/dl, aspartate aminotransferase 21 U/L (5-45 U/L), alanine aminotrasferase 18 U/L (5-45 U/L) and ALP 172 KAU/dl. Serum calcium was 10.2 mg/dl and phosphorus was 5.6 mg/dl. His 24 h urinary calcium excretion was 54 mg, phosphorus excretion was 450 mg and creatinine excretion was 306 mg. Blood urea was 36 mg/dl and serum creatinine was 1.0 mg/dl. Serum sodium was 134 meq/l and potassium was 5.7 meq/l and serum osmolality was 275 mosm/kg. His 24 h urinary protein excretion was 1512 mg. His thyroid profile (free T3 (FT3), free T4 (FT4) and Thyroid stimulating hormone) was within normal limits. His anti-Thyroperoxidase antibodies were negative. Basal serum cortisol was 16.7 μg/dl and the standard short adrenocorticotrophic hormone-stimulated cortisol was 39.5 μg/dl and glycosylated hemoglobin was 13.5%. Celiac disease was ruled out with anti-transglutaminase negative. ultrasonography revealed Grade I fatty change of the liver and b/l kidneys showed increased cortical echogenicity. Radiological examination was normal.
Our patient presented with uncontrolled diabetes mellitus of 10 years duration. He had severe growth retardation, pubertal delay, hepatomegaly and diabetes-related microvascular disease (proliferative retinopathy and nephropathy). Based on these findings, a diagnosis of Mauriac syndrome was made.
Mauriac syndrome occurs in males and females equally, and is most common in adolescence, although there are reports in children as young as toddlers and in adults. It is associated with hepatomegaly and diabetic dwarfism. The actual cause is unknown, but it is probably a combination of factors including inadequate glucose uptake and utilization in the tissues, decreased insulin-like growth factor-1 and growth hormone levels, impaired bioactivity of these hormones, a circulating hormone inhibitor, resistant or defective hormone receptors, insulin deficiency, poor glycemic control, concurrent autoimmune diseases, decreased caloric intake and/or eating disorders. Autoimmune diseases that are more common include Addison's disease, autoimmune gastritis, celiac disease and hypothyroidism. Before treatment with long-acting insulin, delays in growth and sexual maturity were common but generally modest; but, nowadays, with better treatment modalities, this syndrome is rarely seen.
Liver biopsy in the setting of Mauriac syndrome demonstrates steatosis and glycogen deposition, although findings can vary in presentation. Poor T1DM control leads to fatty acid transport to the liver due to hyperglycemia and low insulin levels, which causes hepatomegaly and characteristic liver biopsy findings. These findings reverse with improved glycemic control. Liver biopsy may be warranted in any patient with T1DM and positive autoimmune markers in order to rule out autoimmune hepatitis. The hepatomegaly seen in Mauriac syndrome is not seen in newly diagnosed patients who have been severely insulin deficient because it appears that periods of supraphysiologic insulin levels are associated with the hepatomegaly. Hypertension has never been reported in any of the previous cases of Mauriac syndrome, and, in our case, may be secondary to overt diabetic nephropathy.
To conclude, Mauriac syndrome is a rare complication of poorly controlled diabetes mellitus in adolescence, but the treating physician should keep a high index of suspicion for this so that proper growth can be accomplished with timely intervention.
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