Heterotaxy syndrome with agenesis of dorsal pancreas and diabetes mellitus: case report and review of the literature

Abstract

Heterotaxy syndrome (HS) is a rare congenital condition with multifactorial heritance, characterized by an abnormal arrangement of thoraco-abdominal organs and vessels. Patients present with multiple cardiac, gastrointestinal, hepatosplenic, pancreatic, renal, neurological and skeletal disorders without any pathognomonic alteration. Despite the described increased risk of diabetes mellitus (DM) in patients with altered pancreatic anatomy, just one case was reported in Korea regarding the association of HS and DM in a 13-year-old girl. Our report refers to a 40-year-old female Brazilian patient with a history of DM and HS with polysplenia and agenesis of dorsal pancreas without cardiac abnormalities. She presented a worsening glycemic control associated with weight gain and signs of insulin resistance. After a proper clinical management of insulin and oral medications, our patient developed an improvement in glycemic control. Although it is a rare disease, HS with polysplenia and pancreatic disorders can be associated with an increased risk of DM. This case highlights the importance of investigating DM in patients with HS, especially those with pancreatic anatomical disorders, for proper clinical management of this rare condition.

Use of hyperglycemic clamp to assess pancreatectomy and islet cell autotransplant in patient with heterotaxy syndrome and dorsal pancreas agenesis leading to chronic pancreatitis

“…At diagnosis, she presented with a clamp‐determined FBM that was 50% higher than the average in normoglycemic controls. This finding is at variance with previous cases of HS and DPA that were associated with diabetes 13,14 . Also, in isolated DPA, more than half of patients have diabetes at the time of diagnosis 5,6 .…”

“…This finding is at variance with previous cases of HS and DPA that were associated with diabetes. 13,14 Also, in isolated DPA, more than half of patients have diabetes at the time of diagnosis. 5,6 For these reasons, deceased donors with DPA are in general not considered suitable for whole organ pancreas transplantation and are also discouraged from islet isolation; one report, however, did mention a successful islet cell allotransplantation following isolation from a deceased donor with partial DPA.…”

“…15 At present, it is unclear whether the reported association with diabetes is due to the initial developmental defect and DPA itself or to the subsequent pancreatitis. 5,6,13,14 It is conceivable that the reduced pancreas mass in DPA does not obstruct the development of a normal FBM, 16 but that this FBM becomes threatened by recurrent bouts of pancreatitis with which DPA is associated, 5,6 and which can impair both pancreatic endocrine and exocrine functions. 17 In this case, the retrieved organ yielded an islet cell isolate that The method for reconstructing gastrointestinal continuity may also have influenced the outcome of the implant.…”

“…For these reasons, deceased donors with DPA are in general not considered suitable for whole organ pancreas transplantation and are also discouraged from islet isolation; one report, however, did mention a successful islet cell allotransplantation following isolation from a deceased donor with partial DPA 15 . At present, it is unclear whether the reported association with diabetes is due to the initial developmental defect and DPA itself or to the subsequent pancreatitis 5,6,13,14 . It is conceivable that the reduced pancreas mass in DPA does not obstruct the development of a normal FBM, 16 but that this FBM becomes threatened by recurrent bouts of pancreatitis with which DPA is associated, 5,6 and which can impair both pancreatic endocrine and exocrine functions 17 …”

The diagnostic potential of targeted imaging of the fetal pancreas

“…For example, parental counselling would include the likelihood of congenital diabetes mellitus and malabsorption in a case involving pancreatic agenesis, or the likelihood of recurrent pancreatitis and increased risk for neoplasia of the residual pancreas in a case involving dorsal agenesis of the pancreas. [17][18][19][20] Several studies have reported the association between the TCF2 (HNF1B) gene and fetal renal malformations and agenesis or hypoplasia of the pancreas. [21][22][23] In these cases, however, the pancreatic malformation was not diagnosed prenatally but following postmortem examinations of the abortus.…”