Endocrine Abstracts

Introduction: Ketosis-prone diabetes (KPD) is an emerging and uncommon form of diabetes characterized by patients who present with diabetic ketoacidosis without any immunological autoantibody to islet antigens of classic type 1 diabetes. KPD is mostly observed in African-American populations. Multiple, severe forms of β-cell dysfunction appear to underlie the pathophysiology of KPD. The PAX4 gene, causing Maturity-onset diabetes of the young (MODY) subtype 9, already has been associated with ketosis-prone diabetes.

Case report: A case report of a 38-year old male African patient with co-inheritance of PAX4 and BLK mutations (MODY 7 and 9) as a cause of ketosis prone diabetes is presented to illustrate the clinical manifestations and difficulties in management. The patient was hospitalized as an emergency with metabolic acidosis, partial respiratory compensation with hypocapnia and initial renal failure. Under intensive medical therapy the metabolic situation could be normalized. MODY genes type 1–11 were analyzed.

DNA-Sequencing revealed two mutations: PAX4 gene, exon 1, PAX4,c.109C>T,p.(Arg37Trp); reference sequence NM_006193.2) and BLK gene exon 5, BLK,c.335T>C, p.(Phe112Ser); reference sequence NM_001715.2). The amino acid position 37 in the PAX4 gene is located in an evolutionarily highly conserved sequence motif across many species boundaries and the amino acid position 112 in the BLK gene is located in the functional SH3-domain of the BLK protein. We describe clinical, biochemical and genetic features of the patient.

Conclusions: Identification of the underlying genetic causes of KPD will give a better view of the mechanisms that contribute to the pathophysiology of the disease. Furthermore, proper identification may improve options to prevent KPD.

The results of the genetic analysis are discussed in the context of the clinical findings.