Early-onset glycogenic hepatopathy in a child amidst the era of newer insulin analogs

Glycogenic hepatopathy or Mauriac syndrome (MS), first described in 1930 by Pierre Mauriac in a 10-year-old girl with elevated liver enzymes due to reversible accumulation of excess glycogen in the hepatocytes, represents a triad of growth failure, delayed puberty, and hepatomegaly in children with uncontrolled type 1 diabetes mellitus (T1DM) and occasionally type 2 diabetes mellitus.^[1] Less than150 cases have been reported in the literature.^[2]

A 7-year-old boy, known case of T1DM with four episodes of diabetic ketoacidosis (DKA) in the past 3 years, presented with poor insulin compliance, failure to thrive (height −3.3z), and a recent episode of moderate DKA (pH 7.20 [7.35–7.45], HCO₃ 9.3 mmol/L [22–28]) requiring mechanical ventilation. His glycated hemoglobin was 11.9% (<5.7%). Clinical examination demonstrated massive hepatomegaly (liver span 18 cm, 10 cm below the costal margin) [Figure 1]. Liver function tests showed aspartate aminotransferase and alanine aminotransferase of 139 U/L and 136 U/L (<40), respectively, with normal synthetic function. Ultrasound abdomen revealed a hyperechoic liver parenchyma. Liver biopsy showed enlarged hepatocytes having rarefied cytoplasm filled with periodic acid-Schiff-positive [Figure 2a] and diastase-sensitive [Figure 2b] glycogen, along with moderate macrovesicular steatosis [Figure 3], and absence of any marked periportal fibrosis – consistent with hepatic glycogenosis of MS. Daily insulin dose was subsequently titrated to achieve adequate glycemic control with complete resolution of hepatomegaly and transaminitis over a follow-up of 2.5 months.

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Figure 1:

Massive hepatomegaly in the index case (depicted by black outline).

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Figure 2:

(a) Liver biopsy showing normal hepatic architecture with mildly enlarged, pale pink hepatocytes having increased cytoplasmic volume and glycogenated nuclei [black arrow, Hematoxylin and eosin (H&E), ×20] (b) Liver biopsy after periodic acid-Schiff-D stain showing clearing of glycogen with “ghost cells” (blue arrow, H&E, ×20).

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Figure 3:

Liver biopsy showing macrovesicular steatosis, (Hematoxylin and eosin, ×20).

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MS has become exceedingly rare with modern long-acting insulin analogs and structured diabetic education, with our case being the second one to be reported in the first decade of life.^[3] Pathogenesis involves alternating hyperglycemia and over-insulinization with short-acting analogs, leading to insulin-independent hepatic glucose uptake by GLUT2 and subsequent polymerization of glucose 6-phosphate into glycogen by glycogen synthase.^[4,5] Cases with MS are more predisposed to develop recurrent DKA, as in our case.^[1] With improved glycemic control and structured insulin therapy, hepatomegaly and transaminase elevation are reversible, emphasizing early recognition.