Mauriac syndrome: A failure of parent or physician

Introduction

Mauriac syndrome (MaS) is a rare complication of poorly controlled type 1 diabetes (T1DM) characterised by short stature, cushingoid facies, abdominal protuberance, delayed puberty and deranged liver function (with raised transaminase levels) and glycogen accumulation in the liver on histology.

The glycogen hepatopathy may be a part of MaS or independent of it. ¹ Hyperglycaemia and varying insulin levels lead to trapping of glucose inside the hepatocyte, where it is stored as glycogen. The pathogenesis of this entity is poorly understood, and some genetic predisposition is suggested leading to altered activity of the glycogen phosphorylase enzyme complex. The disease responds well to adequate control of glycaemia, dietary management and adherence to therapy.^2,3 We describe our experience of this entity at our centre over the last 15 years.

Material and methods

Our study was a retrospective analysis of case records at our tertiary care health facility in northern India. Nine patients fitting the clinical definition of MaS were identified. MaS was defined by clinical criteria of type T1DM, hepatomegaly, growth failure and elevated liver enzymes twice the upper limit of normal. Other common causes, such as viral hepatitis, autoimmune hepatitis, coeliac disease and thyroid dysfunction, were excluded in all cases with relevant investigations.

The records were reviewed for the age of presentation, duration of T1DM, episodes of past diabetic ketoacidosis, levels of hepatic enzymes, lipid profile, insulin dosages and growth parameters such as weight, height and body mass index Z scores. The data for microvascular complications, specifically retinopathy and nephropathy, macrovascular complications and neuropathies, were also collected.

Descriptive data are described as frequency and percentages; quantitative data are expressed as mean and standard deviation for normally distributed data and median with interquartile range for skewed distributions.

Results

The median age of presentation was 7.6 years (range: 2.8–13), and five out of nine patients were male. The median duration of T1DM was 36 months (range: 18–50), and the majority (6 out of 9) of the patients were on isophane, regular or mixtard (biphasic short- and long-acting) insulin.

Poor glycaemic control (mean HbA1c 13 ± 2.08%, normal range 4.4–5.6%), diabetic ketoacidosis in two and systemic infection in another two were the presenting features in the cohort. All children were undernourished (median weight for age Z score −2.2 (IQR −3.95 to −1.69)) and stunted (median height for age Z score −3.04 (IQR −4.39 to −2.42)).

All patients had poor compliance to diabetes management, and the median duration of loss of follow-up period was 30 months (range: 11–66) (Table 1). There was hepatomegaly in all patients, the median liver span being 14 cm, demonstrating a normal echotexture on ultrasonography in six, heterogeneous in two, and grade 1 fatty liver in one patient.

OPEN IN VIEWER

Table 1.

Clinical and lab characteristics of children with Mauriac syndrome.

Patient no.	Age (years) and sex	Duration of disease (months)	Presenting complaints	Lost to follow-up (months)	Insulin regimen	Wt Z score	Ht Z score	AST/ ALT	ALP (40–150 U/L)	Liver size cm (USG)	Liver echotexture	HbA1C	Chol (mmol/L)	TG (mmol/L)	LDL (mmol/L)	HDL (mmol/L)
1	3, M	36	Poor glycaemic control	30	Basal Bolus	−3.95	−5.64	49/42	188	12	Normal	12	4.92	3.65		0.88
2	9, F	36	Poor glycaemic control	72	Basal Bolus	−1.7	−2.52	157/104	256	15.1	Normal	9	5.39	3.20		0.98
3	5, M	36	DKA	60	Basal Bolus	−3.96	−3.15	237/154	176	16.4	Normal	15.1
4	7, M	12	Poor glycaemic control	48	Pre-mixed	−1.57	−2.33	17/17	171	12.4	Normal	15.6	8.21	2.10	6.29	1.92
5	13, F	9	Poor glycaemic control	108	Mixed split	−5.95	−6.18	45/25	192	15	Normal	13	5.15	1.39		1.81
6	2.8, M	24	DKA	12	Mixed split	−1.4	−1.97	102/69	281	13	Grade 1 fatty	13.1	6.97	5.15		0.85
7	10, M	48	Subcutaneous infection  (pyoderma of arm)	9	Pre-mixed	−3.21	−2.55	168/102	315	16	Heterogenous	11.3
8	11, M	114	Abdominal distention	12	Pre-mixed	−1.95	−3.1	105/78	255	14	Normal	10.9	5.52	1.37	3.86	1.53
9	8, M	52	Poor glycaemic control	10	Mixed split	−2.2	−3.04	118/96	236	17	Heterogenous	13.7	4.53	1.38	3.13	1.64

All patients had raised transaminase levels with median AST 105 (range: 47–162; normal values 2–41) U/L and ALT 78 (range: 34–103; normal range 2–41) U/L, but synthetic function was normal in all. One child had microalbuminuria, and one had posterior subcapsular cataract at presentation. Dyslipidaemia was present in all with mean values of cholesterol, triglyceride, LDL and HDL being 5.8 ± 1.3 (range: 3.9–4.4) mmol/L, 2.6 ± 1.4 (range: 0.6–1.0) mmol/L, 4.4 ± 1.6 (range: 1.8–2.9) mmol/L and 1.4 ± 0.4 (range: 0.9–1.4) mmol/L, respectively (Table 1). Unfortunately, the majority of patients were lost to follow-up even after multiple diabetic education and counselling sessions.

Discussion

Mauriac syndrome is a disease of adolescents; there are few case reports in pre-school children. However, the age of disease presentation is much lower in our study. The lack of clinical care facilities and finances probably alter the timeline of complications for a chronic disease.^4–6

Poor growth in diabetes may occur due to comorbidity with coeliac disease or hypothyroidism as seen in our cohort; and growth hormone-Insulin like growth factor (GH-IGF) axis abnormalities due to low portal vein insulin and poor glycaemic control. While children with MaS in rich countries reach their target height or just slightly below, their Indian counterparts report 18% children falling below 2SDs at their final height. Long-term data in MaS are sparse due to the rarity of the condition and poor follow-up.^7,8

Glycogen hepatopathy is an underrecognised entity which may be present without the other manifestations of Mauriac syndrome and improves with intensive insulin therapy and good metabolic control.^9,10

Diabetes care among children requires continuous commitment, financial support and education; lapses in any of these result in poor compliance and complications related to the disease. In the modern era of abundant insulin supply, better technology for glucose monitoring, MaS is rare outside low-resource settings.

Failure to deliver adequate quality diabetes care remains an enigma, the stubbornness of certain patients to access care or a genetic predisposition responsible for MaS require more detailed research and action.