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.