Diabetic Ketoacidosis in a Young Girl with Dorsal Pancreatic Agenesis and Negative Maturity-Onset Diabetes of the Young (MODY) Gene Panel: Expanding the Spectrum of Non-Autoimmune Diabetes: A Case Report

Seba Miriam David¹, Athulya G Asokan^2*, Akshay Raju³

¹Senior Resident, Department of General Medicine, Government Medical College, Thiruvanathapuram, Kerala, India
²Assistant Professor, Department of General Medicine, Government Medical College, Kottayam, Kerala, India
³Senior Resident, Department of Rheumatology, Christian Medical College, Vellore, Tamil Nadu, India

*Correspondence author: Athulya G Asokan, MD (General Medicine), Assistant Professor, Department of General Medicine, Government Medical College, Kottayam – 686008, Kerala, India; Email: [email protected]  

Citation: David SM, et al. Diabetic Ketoacidosis in a Young Girl with Dorsal Pancreatic Agenesis and Negative Maturity-Onset Diabetes of the Young (MODY) Gene Panel: Expanding the Spectrum of Non-Autoimmune Diabetes: A Case Report. Arch Endocrinol Disord. 2025;1(2):1-6.

Copyright^© 2025 by David SM, et al. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Table 1: Summary of investigations.

Figure 1: Chest X-ray Showing Multilobar consolidation.

Figure 2: Contrast CT image of abdomen showing dorsal pancreatic agenesis, head and uncinate process seen.

Figure 3: MRCP image showing dorsal pancreatic agenesis.

Hospital Course

The patient was admitted to the intensive care unit and managed per standard DKA protocol with intravenous fluids, regular insulin infusion and empirical antibiotics (ceftriaxone and azithromycin). Her acidosis resolved within 48 hours (repeat ABG pH 7.46, HCO₃⁻ 26.7 mmol/L). She was transitioned to basal-bolus insulin therapy and started on pancreatic enzyme replacement. At three-month follow-up, she had gained 3 kg, maintained good glycemic control and remained asymptomatic.

Discussion

Dorsal Pancreatic Agenesis (DPA) is an exceptionally rare congenital anomaly characterized by the absence of the pancreatic body and tail due to failed development of the dorsal pancreatic bud, with fewer than 100 cases reported globally [6,7,11]. Because the dorsal pancreas contains a substantial proportion of islet cell mass, its agenesis predisposes individuals to both endocrine and exocrine dysfunction. In our patient, cross-sectional imaging Contrast-Enhanced Computed Tomography (CECT) and Magnetic Resonance Cholangiopancreatography (MRCP) confirmed complete agenesis of the dorsal pancreas and the markedly reduced stool pancreatic elastase (64.2μg/g) indicated severe exocrine insufficiency, consistent with previous reports [1,8,12]. At presentation, the patient fulfilled diagnostic criteria for DKA with severe hyperglycemia (634 mg/dL), elevated HbA1c (12.5%), high-anion gap metabolic acidosis and ketonuria. Although DKA is classically associated with autoimmune type 1 diabetes, it is distinctly uncommon in structural pancreatic anomalies or monogenic diabetes because residual β-cell reserve generally suppresses ketogenesis [3,5]. In this case, multilobar pneumonia, evidenced by chest radiograph, elevated CRP and neutrophilic leukocytosis, acted as a potent physiologic stressor precipitating metabolic decompensation. Infection-related DKA has similarly been documented in other cases of DPA and in non-type 1 diabetes phenotypes [3,4,13,14].

The absence of pancreatic autoantibodies effectively excluded autoimmune T1DM, prompting evaluation for alternative etiologies. The negative MODY gene panel, which included PDX1, HNF1A, HNF4A and other β-cell transcription factor genes, ruled out known monogenic diabetes forms. Although PDX1 (IPF1) mutations are well recognized in MODY 4 and pancreatic hypoplasia or agenesis multiple studies have reported DPA in patients without identifiable genetic variants [9,10,15]. Increasing evidence implicates additional developmental genes such as PTF1A, RFX6, GATA6 and NEUROD1 in pancreatic organogenesis and agenesis phenotypes [16-18]. Our findings therefore highlight the limitations of currently available genetic panels and underscore the need for expanded genomic approaches, including whole-exome and whole-genome sequencing.

The patient’s hospital course reinforces the functional consequences of the structural defect identified. Early DKA management led to resolution of acidosis within 48 hours and initiation of pancreatic enzyme replacement addressed exocrine insufficiency. At three months, the patient exhibited weight gain, improved glycemic control and absence of recurrent symptoms, demonstrating the importance of timely recognition and targeted management of DPA-related metabolic derangements.

Overall, this case expands the phenotypic spectrum of non-autoimmune diabetes in adolescents and emphasizes that DPA should be considered in young, non-obese, antibody-negative individuals presenting with DKA, especially when accompanied by exocrine insufficiency or atypical features. Comprehensive structural imaging and functional pancreatic assessment are critical components of evaluation. Even when MODY gene testing is negative, congenital anomalies such as DPA remain important etiologies and ongoing genomic research is likely to reveal additional developmental pathways implicated in these rare presentations (Table 2).

Table 2: A flow chart showing evaluation of an young patient with diabetes.

Conclusion

Dorsal pancreatic agenesis is an uncommon but clinically important structural cause of non-autoimmune diabetes in adolescents. This case demonstrates that diabetic ketoacidosis, although rarely described in congenital pancreatic anomalies, can occur when limited β-cell reserve is compromised by acute metabolic stress such as infection. The strength of this report lies in its comprehensive evaluation combining autoantibody testing, exocrine function assessment, advanced imaging and extensive MODY gene analysis which allowed precise etiological classification and avoided misdiagnosis as type 1 diabetes. This integrated approach reinforces the need to consider anatomical abnormalities in young patients presenting with atypical, antibody-negative hyperglycemia. However, as a single-patient observation, broader generalizability is limited and the absence of extended genomic studies (such as whole-exome or whole-genome sequencing) limits exploration of the underlying developmental genetics. Likewise, the relatively short follow-up period restricts long-term insights into metabolic and exocrine outcomes. Despite these limitations, this case expands the phenotypic spectrum of MODY-negative, non-autoimmune diabetes and underscores the need for heightened clinical vigilance. Early recognition of dorsal pancreatic agenesis can guide targeted therapy, inform genetic counseling and improve long-term management in similar atypical presentations.

Learning Points

• Dorsal Pancreatic Agenesis (DPA) is a rare but important structural cause of non-autoimmune diabetes and should be considered in adolescents presenting with antibody-negative hyperglycemia
• Diabetic ketoacidosis can occur in DPA, especially when limited β-cell reserve is stressed by intercurrent illness such as infection
• Comprehensive evaluation including pancreatic imaging and stool elastase is essential to differentiate structural pancreatic defects from type 1 diabetes, type 2 diabetes and monogenic diabetes
• A negative MODY gene panel does not exclude congenital pancreatic anomalies, as several developmental genes remain under-recognized or not covered in standard sequencing platforms
• Management must address both endocrine and exocrine insufficiency, with insulin therapy and pancreatic enzyme replacement improving clinical outcomes
• Early diagnosis enables accurate counseling, long-term monitoring and appropriate family screening, particularly in atypical presentations with preserved C-peptide and absent autoimmunity

Conflict of Interest

The authors declare that they have no conflict of interest.

Financial Disclosure

This research did not receive any grant from funding agencies in the public, commercial or not-for-profit sectors.

Authors Contributors

All the authors have made contributions in their own way.

Acknowledgment

The authors would like to thank the Department of Radiology for helping with advanced imaging interpretation and the Clinical Laboratory Services for making timely genetic and biochemical evaluations possible. Additionally, we are grateful to the patient and her family for their cooperation and permission, which enabled the publication of this report. The authors acknowledge the support of their institution in enabling multidisciplinary care and academic documentation of this rare clinical presentation. The authors acknowledge the use of ChatGPT (OpenAI) to assist in language refinement and editing. The authors reviewed and approved all generated content and took full responsibility for the final manuscript.

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