Mauriac syndrome is a rare complication of type 1 diabetes characterized by extreme liver enlargement due to glycogen deposition, along with growth failure and delayed puberty. It occurs in some children and adolescents with type 1 diabetes irrespective of their glycemic control. History
Mauriac syndrome was first described in 1930 by Pierre Mauriac. It was described as a syndrome of growth failure and delayed puberty in children with poorly-controlled type I diabetes. Signs and symptoms
Patients with Mauriac syndrome may present with obesity, hepatomegaly, cushingoid facies, and elevated liver enzymes. Patients usually have growth failure and delayed puberty, which should warn the physician about insufficient management of the patients diabetes. These symptoms can be reversed with good glycemic control. Genetics
Abnormally high blood sugar levels are relatively common among patients with type I diabetes, but Mauriac syndrome is rare. This suggests that high blood sugar is not the only factor necessary to cause the syndrome. A study of an adolescent boy with severe Mauriac syndrome found a mutation in PHKG2, which is the catalytic subunit of the enzyme glycogen phosphorylase kinase (PhK). PhK is a large enzyme complex responsible for the activation of glycogen phosphorylase, the first enzyme in the pathway of glycogen metabolism. This childs mutation inhibited glycogen metabolism and caused increased glycogen deposition in the liver. The childs mother had the mutant enzyme, but no liver enlargement. The childs father had type 1 diabetes. Neither parent had Mauriac syndrome.
Porphyrias are classified in two ways, by symptoms and by pathophysiology. Physiologically, porphyrias are classified as liver or erythropoietic based on the sites of accumulation of heme precursors, either in the liver or in the bone marrow and red blood cells.Deficiency in the enzymes of the porphyrin pathway leads to insufficient production of heme. Heme function plays a central role in cellular metabolism. This is not the main problem in the porphyrias; most heme synthesis enzymes—even dysfunctional enzymes—have enough residual activity to assist in heme biosynthesis. The principal problem in these deficiencies is the accumulation of porphyrins, the heme precursors, which are toxic to tissue in high concentrations. The chemical properties of these intermediates determine the location of accumulation, whether they induce photosensitivity, and whether the intermediate is excreted (in the urine or feces).There are eight enzymes in the heme biosynthetic pathway, four of which—the first one and the last three—are in the mitochondria, while the other four are in the cytosol. Defects in any of these can lead to some form of porphyria. The hepatic porphyrias are characterized by acute neurological attacks (seizures, psychosis, extreme back and abdominal pain, and an acute polyneuropathy), while the erythropoietic forms present with skin problems, usually a light-sensitive blistering rash and increased hair growth.Variegate porphyria (also porphyria variegata or mixed porphyria), which results from a partial deficiency in PROTO oxidase, manifests itself with skin lesions similar to those of porphyria cutanea tarda combined with acute neurologic attacks.