Introduction
Maturity-onset diabetes of the young (MODY) is a group of monogenic diabetes (MD) characterized by an autosomal dominant inheritance. MD is a specific type of diabetes resulting from single-gene mutations that play a key role in the development, function, and insulin signalling pathway of pancreatic β-cells. It accounts for approximately 1 to 5% of all types of diabetes [1,2] and mainly includes MODY, neonatal diabetes, mitochondrial gene mutation diabetes, adipose atrophic diabetes and others. Besides, insulin resistance syndrome caused by a single-gene mutation presenting with diabetes as one of the main clinical manifestations also belongs to the category of monogenic diabetes. Among them, MODY accounts for approximately 1% of the total population with diabetes, and about 1 to 2% of diabetes in the Chinese population [3]. The population characteristics of MODY mainly include an early onset before the age of 25, confirmed family history of multiple generations with diabetes together with an autosomal dominant inheritance pattern. Recent data show that MODY1 is the first-named MODY subtype, and its pathogenic gene is the hepatocellular nuclear factor (HNF), namely, 4α. It was first named in 1996 by the Japanese scholar Yamagouta et al. [4]. With the continuous progress of research, 14 MODY pathogenic genes have been found so far, and correspondingly 14 subtypes have been classified. They are hepatocyte nuclear factor 4α, HNF-4α, MODY1, glucokinase, GCK, MODY2, hepatocyte nuclear factor 1α HNF-1α, MODY3, insulin promoter factor 1,I PF-1, MODY4, hepatocyte nuclear factor 1β, HNF1-β, MODY5, neurogenic differentiation factor, NEUROD-1, MODY6, kruppel-like factor 11, KLF-11, MODY7, carboxyl-ester lipase, CEL, MODY8, paired-homeodomain transcription factor, PAX-4, MODY 9, insulin gene, INS, MODY10, B-lymphocyte kinase, BLK, MODY11, ATP-binding cassette, sub-family C member 8, ABCC8, MODY12, potassium inwardly-rectifying channel, subfamily J member 11, KCAJ-11, MODY13 and adaptor protein, phosphotyrosine-interacting PH domain and leucine zipper 1, APPL1, and MODY14. Among them, the most common types in the Chinese population are MODY1, MODY2, and MODY3, respectively [5]. Relevant research data show that about 16 to 45% of MODY gene loci have not been recognized so far and are currently temporarily called candidate genes of MODY-X. Possible candidate genes include paired box gene 6, PAX6, hepatocyte nuclear factor-3β, HNF-3β, Kappa2.2, NKX 2.2, Neurogenin3, Ngn3, and Nuclear transcription factor, NFX6.1 [6-8].
Due to the atypical clinical manifestations of MODY, pediatricians face serious difficulties in the clinical understanding of the disease. In clinical practice, MODY is often misdiagnosed as type 1 or type 2 diabetes, and therefore receive inappropriate overtreatment. Typical MODY cases are characterized by an early onset before the age of 25, pancreatic β-cell functional disorder and other features [9]. Recent data show that patients with MODY account for about 1 to 2% of all children diagnosed with diabetes. Interestingly, in these patients, the pancreatic autoantibodies are negative while the serum levels of C-peptide usually are in the normal range or slightly lower, which allows the distinction of MODY from type 1 diabetes. Normally, MODY patients are not obese and are therefore distinguished from type 2 diabetes patients. Research in this field has discovered 14 kinds of MODY subtypes so far. Therefore, for accurate treatment, prognostic evaluation and prenatal consultation, it is of great significance to precisely distinguish MODY patients from those with type 1 and 2 diabetes.
MODY9, first reported in 2007 [10], is caused by a mutation in the Paired box gene 4 (PAX4) and is a rare type of MODY. PAX4, a member of the PAX transcription factor family, is an important regulator of early pancreatic development in the embryonic stage and plays an important role in the differentiation and development of islet β -cells [11]. Research data show that the incidence of MODY9 in populations with MODY is low. So far, only a few families have been reported with no confirmed case of MODY9 in China.
Here, we report on a case of a Chinese MODY9 patient diagnosed and treated at the Department of Endocrinology at Beijing Children hospital. We further discuss the relevant literature to improve clinicians’ understanding of this disease and to propose modern approaches for precise and on time MODY9 diagnosis.