Renata Peixoto‑Barbosa1,2, André F. Reis1 and Fernando M. A. Giuffrida1,2
1 Disciplina de Endocrinologia, Centro de Diabetes, Universidade Federal de
São Paulo (UNIFESP), Rua Estado de Israel, 639–Vila Clementino, São Paulo,
SP CEP: 04022‑001, Brazil. 2 Departamento de Ciências da Vida, Universidade
do Estado da Bahia (UNEB), Salvador, Brazil.
Abstract
Background: Maturity-onset diabetes of the young (MODY) is the most common type of monogenic diabetes,
being characterized by beta-cell disfunction, early onset, and autosomal dominant inheritance. Despite the rapid
evolution of molecular diagnosis methods, many MODY cases are misdiagnosed as type 1 or type 2 diabetes. High
costs of genetic testing and limited knowledge of MODY as a relevant clinical entity are some of the obstacles that
hinder correct MODY diagnosis and treatment. We present a broad review of clinical syndromes related to most common
MODY subtypes, emphasizing the role of biomarkers that can help improving the accuracy of clinical selection
of candidates for molecular diagnosis.
Main body: To date, MODY-related mutations have been reported in at least 14 different genes. Mutations in glucokinase
(GCK), hepatocyte nuclear factor-1 homeobox A (HNF1A), and hepatocyte nuclear factor-4 homeobox A (HNF4A)
are the most common causes of MODY. Accurate etiological diagnosis can be challenging. Many biomarkers such as
apolipoprotein-M (ApoM), aminoaciduria, complement components, and glycosuria have been tested, but have not
translated into helpful diagnostic tools. High-sensitivity C-reactive protein (hs-CRP) levels are lower in HNF1A-MODY
and have been tested in some studies to discriminate HNF1A-MODY from other types of diabetes, although more
data are needed. Overall, presence of pancreatic residual function and absence of islet autoimmunity seem the most
promising clinical instruments to select patients for further investigation.
Conclusions: The selection of diabetic patients for genetic testing is an ongoing challenge. Metabolic profiling,
diabetes onset age, pancreatic antibodies, and C-peptide seem to be useful tools to better select patients for genetic
testing. Further studies are needed to define cut-off values in different populations.
Keywords: Diabetes mellitus, Maturity-onset diabetes of the young, Biomarkers, Genetics, Monogenic diabetes
https://dmsjournal.biomedcentral.com/articles/10.1186/s13098-020-00557-9