Introduction:Gallbladder agenesis (GA) is often misdiagnosed as a gallbladder pathology. This systematic review aimed to summarize the current evidence on epidemiology, clinical presentation, diagnostic approaches, and management strategies.Methods:PubMed/MEDLINE, Scopus, and Embase databases were comprehensively searched in English, French, and Spanish for GA cases published before November 2022. Two reviewers screened articles using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were analyzed to identify the clinical features, diagnostic approaches, management strategies, and associated factors.Results:A total of 9186 unique articles were screened, 125 of which met the inclusion criteria (151 cases in total). Most patients were female (66%), with a median age of 45 years. Most patients (73%) were diagnosed intraoperatively, and the most common presenting symptoms were right upper quadrant pain (66%), nausea (32%), or emesis (30%). Less than 15% of patients had elevated liver enzyme levels or leukocytosis. Ultrasonography was the primary imaging modality (81%). Most patients (79%) underwent operative management, with laparoscopy in 49.6% and exploratory laparotomy in 50.4%. Diagnosis by hepatobiliary iminodiacetic acid scan was associated with higher complications (odds ratio 8.53, 95% confidence interval 1.21–59.1, P = 0.026). There were more complications in the US cohort than in the non-US cohort (20% vs. 4.5%, P = 0.006).Conclusions:This systematic review showed that many patients with GA underwent unnecessary operative interventions with an associated increase in complications. Surgeons should be familiar with this diagnosis to minimize unnecessary interventions and reduce healthcare costs.

Intraoperative diagnosis of gallbladder agenesis

Gallbladder agenesia is a rare congenital anomaly that is frequently overlooked in clinical practice, often misdiagnosed as chronic sclero-fibrous cholecystitis or cholelithiasis. Failure to recognize it intraoperatively can prompt unnecessary and hazardous exploration of the biliary tree and liver, increasing the risk of iatrogenic injuries.

Patient: Male, 38-year-oldFinal Diagnosis: Gallbladder agenesisSymptoms: Hematemesis • lightheaded • right upper quadrant pain • syncopeClinical Procedure: —Specialty: Anatomy • Gastroenterology and HepatologyObjective: Rare diseaseBackgroundGallbladder agenesis is a rare congenital anomaly resulting from failed cystic bud development or canalization during early embryogenesis. While frequently asymptomatic, up to half of patients develop postprandial right upper-quadrant pain resembling biliary colic. This report describes an unusual case of gallbladder agenesis in a 38-year-old man with Klinefelter syndrome who presented with hematemesis and right upper-quadrant pain.Case ReportA 38-year-old man with known Klinefelter syndrome (47, XXY) and no prior abdominal surgery presented with hematemesis, lightheadedness, syncope, and right upper-quadrant pain. Laboratory testing revealed mild transaminitis, elevated ferritin, and normal bilirubin. Computed tomography angiography initially revealed hepatic steatosis and splenomegaly, and no gallbladder was visualized on hepatobiliary iminodiacetic acid scan and ultrasound. Esophagogastroduodenoscopy showed mild antral gastritis and a small hiatal hernia without active bleeding. Gallbladder agenesis was confirmed by magnetic resonance cholangiopancreatography. The patient’s hematemesis resolved spontaneously, and he was discharged in stable condition with hepatology follow-up.ConclusionsThis case highlights the diagnostic value of MRCP in confirming gallbladder agenesis and avoiding unnecessary surgical exploration. Hematemesis as the initial presentation is highly atypical, suggesting a potential but unproven link between gallbladder agenesis and upper-gastrointestinal bleeding. Additionally, this report presents the first known coexistence of GA and Klinefelter syndrome, raising the possibility of a subtle developmental correlation between chromosomal nondisjunction and endodermal organogenesis. Recognition of such rare presentations expands the phenotypic spectrum of Klinefelter-associated hepatobiliary abnormalities and underscores the need for awareness of gallbladder agenesis in patients with biliary-type pain but no visible gallbladder on imaging.

Living Liver Donor with Gallbladder Agenesis

Gallbladder Agenesis: A Case Report and Review of the Literature

Gallbladder agenesis (GA) is a very rare biliary tract anomaly. Between 50% and 70% of patients are asymptomatic. It is usually diagnosed during the radiological examination of patients with dyspeptic complaints or during the operation. In this study, a 55-year-old female patient presented at our clinic for dyspepsia and was diagnosed with gallbladder agenesis. The patient was admitted to the clinic with complaints of epigastric pain, which did not correspond with times of fasting or fullness. There was no disease or complaint in the patient's history. Cholestasis enzymes, bilirubin and other laboratory values were normal. Abdominal ultrasonography (US) performed with the preliminary diagnosis of cholelithiasis revealed that there was no gallbladder. Gallbladder agenesis was detected in the magnetic resonance cholangiopancreatography (MRCP) examination. The patient was followed up and no surgical intervention was performed. The possibility of other bile duct anomalies, such as choledochal cysts and stones is high in patients with GA. These anomalies can be confused with the gallbladder in abdominal US. The risk of injury to the biliary tract, small intestine, hepatic artery, and portal vein is higher as a result of additional dissections to find the gallbladder in surgical interventions performed in patients with GA. It may be important to keep in mind the rarity of gallbladder agenesis in order to avoid unnecessary surgical interventions, such as laparoscopy and laparotomy, for patients presenting with signs of acute cholecystitis.

Abstract An asymptomatic male Jack Russell terrier diagnosed at the age of 18 weeks with congenital gall bladder agenesis, confirmed by computed tomography scan, after finding abnormally high values for liver enzymes in a routine blood count. Treatment with liver‐protective agents S‐adenosylmethionine and ursodeoxycholic acid was initiated. At 6 months of age, the dog was referred for nutritional consultation, with a diet based on a commercial dry puppy food containing approximately 22% fat in dry matter. We formulated a mixed diet based on a commercial liver diet, whey protein and low‐fat quark. Achieving a lower fat content (13%–13.4% dry matter) to support the nutritional requirements of a growing dog with potentially impaired fat absorption due to the lack of a gall bladder. To our knowledge, this is the first case report focusing on dietetics in canine congenital gall bladder agenesis, highlighting the need for a hepatic diet.

Congenital gallbladder agenesis in a dog: An invisible driver of hepatic and pancreatic pathology

Gallbladder agenesis (GBA) is an extremely rare disease that mimics biliary pathology. More frequent in women, it can occur alone or associated with other malformations. We present the case of a 53-year-old female patient with clinical symptoms compatible with cholelithiasis, with ultrasound reports of scleroatrophic gallbladder. Elective laparoscopic cholecystectomy was performed, with no gallbladder found, and intraoperative cholangiography was performed with the same results. Postoperative magnetic resonance cholangiography confirmed gallbladder agenesis. Finally, the postoperative course was adequate, without complications. GBA commonly presents with typical symptoms of biliary colic and ultrasound diagnosis of cholelithiasis or scleroatrophic gallbladder. Preoperative diagnosis is unlikely. If surgery is performed, laparoscopic examination is preferable. Subsequently, the evolution is generally asymptomatic.

Pathogenic variants in GATA6, GATA4, and PDX1 cause pancreatic hypoplasia or agenesis and early onset diabetes mellitus. There is a lack of information about long-term outcomes and clinical management of these complicated patients, including how best to approach their exocrine pancreatic insufficiency (EPI), weight gain, and glycemic management. We investigated clinical features and treatment of patients with variants in GATA6, GATA4, and PDX1 identified through the US Monogenic Diabetes Registry. Data were self-reported or extracted from medical records. Eleven children were studied. Pancreatic hypoplasia/agenesis, EPI, gallbladder agenesis, and congenital heart defects were common in this cohort. Novel features were present, such as recurrent infections and epilepsy. All participants were born small for gestational age and many had difficulties with weight gain. Insulin treatment was discontinued and later reinstated for 3 infants. Glycemic control in nearly all patients was suboptimal with the mean hemoglobin A1c being 8.7, but only 1 episode of diabetic ketoacidosis was reported. Fasting and postprandial hypoglycemia were common. Eight of 11 children required pancreatic enzymes. Two children required enteral feedings to maintain nutritional balance. Children with GATA6, GATA4, and PDX1-related neonatal diabetes have labile, insulin-dependent diabetes mellitus and varying degrees of EPI caused by pancreatic hypoplasia/agenesis. Intrauterine growth restriction and postnatal difficulties with weight gain are common but rates of diabetic ketoacidosis are low, which may in part be due to a lack of glucagon, an important driver of ketosis.

ObjectiveTo evaluate the postnatal outcomes of referred cases with abnormal findings in the fetal gallbladder (GB) or cysts in the fetal liver.MethodsThis retrospective study included pregnant women referred to a tertiary referral unit, the fetal therapy center at Ulsan Asan Medical Center in Korea, between June 2005 and October 2022. Persistent non-visualization of the fetal gallbladder (NVFGB) was defined as non-visualization at least twice using an ultrasound scan. Antenatal ultrasound findings were obtained from the medical records, and the clinical, radiological, and surgical findings of the babies were reviewed.ResultsA total of 113 referred patients were evaluated. Most enlarged and small GBs were identified as normal or GB stones, sludge, septate GB, or choledochal cysts (CDC). NVFGB was identified postnatally in 77.5% of cases. Persistent NVFGB was identified postnatally as biliary atresia (3/14; 21.4%), hepatic parenchymal disease with cholestasis (2/14; 14.2%), or isolated GB agenesis (6/14; 42.8%). The majority of cysts in the fetal liver cases with visualization of the fetal GB were identified as CDC. Half of the patients (2/4) with CDC who underwent NVFGB were confirmed to have biliary atresia.ConclusionExcept for persistent NVFGB, most abnormal ultrasound findings in fetal GB were associated with good postnatal outcomes. Cysts in the fetal liver with visualization of the fetal GB did not result in serious adverse outcomes. NVFGB, especially persistent NVFGB with or without cysts in the fetal liver, should be followed up closely prenatally and postnatally.

To explore the predictive potential of prenatal ultrasound features and their capacity to differentiate biliary atresia (BA) in fetuses exhibiting biliary abnormalities. Data of pregnant women who underwent routine fetal ultrasound screening during the second trimester (18-27+6weeks) were retrospectively analyzed in the 2018-2022 period. Fetuses with suspected biliary abnormalities in the second trimester were identified, and the cases were categorized into 5 groups: enlarged fetal gallbladder, small fetal gallbladder, non-visualized fetal gallbladder, hepatic hilar cyst, and fetal duplicated gallbladder. Follow-up assessments were conducted in the third trimester and postnatally. Among the 339 cases with suspected fetal biliary abnormalities, 10 cases were postnatally diagnosed with BA. Among them, 2 cases (2.04%, 2/98) were in the small fetal gallbladder group, 3 cases (3.95%, 3/76) were in the non-visualized fetal gallbladder group, and 5 cases (20.83%, 5/24) were in the hepatic hilar cyst group. In the small fetal gallbladder, non-visualized fetal gallbladder, and total suspected fetal biliary abnormalities groups, the incidence of BA increased when accompanied by additional structural abnormalities compared with isolated cases (all p<0.05). Within the small fetal gallbladder and non-visualized fetal gallbladder groups, a consistent feature associated with BA and gallbladder agenesis was the persistence of abnormal gallbladder size despite increasing gestational age. In the group with hepatic hilar cysts, significant prenatal differences between cystic BA and biliary dilatation were observed in cyst morphology, maximum diameter, changes in cyst size with gestational age, and fetal gallbladder size (p<0.05). Cyst morphology, maximum diameter, and gallbladder size demonstrated potential in differentiating cystic BA from biliary dilatation. The combination of these three features achieved a sensitivity of 100% and a specificity of 94.7%. Persistent small or non-visualized fetal gallbladder, along with specific hepatic hilar cyst and other structural abnormalities, are crucial prenatal ultrasound findings for early diagnosis of BA. Early and repeated assessments, incorporating multi-feature observations, are essential for improving differential diagnosis and enhancing optimal outcomes.

Abstract Gall bladder agenesis and ductal plate malformation (DPM) are rarely diagnosed hepatobiliary anomalies in dogs. This case report documents the clinical findings, diagnostic test results and outcome in a 3.5‐year‐old female Rottweiler with gall bladder agenesis associated with DPM. The dog was presented with a 2‐week history of diarrhoea and vomiting. Biochemical test results were consistent with hepatopathy. Abdominal ultrasound revealed absence of a gall bladder, ascites and asymmetrically small liver lobes with irregular contours and a heterogeneous but overall increased echogenicity. Explorative laparotomy confirmed the absence of a gall bladder and small‐sized liver lobes with a very irregular surface and firm consistency. Histological examination of liver biopsies showed severe portal‐to‐portal bridging fibrosis, tortuous and multifocally ectatic bile duct profiles, multifocal absence of portal veins, increased arteriolar profiles, direct intersection of bile ducts with hepatocytes and lymphangiectasia with minimal periportal inflammation, consistent with DPM. The dog developed hepatic encephalopathy and was euthanased.

Two Rare Conditions in One: A Case of Gallbladder Agenesis in a Patient With Type I Choledochal Cyst.

Background: Gallbladder agenesis (GA) is an uncommon congenital condition defined by the absence of the gallbladder and cystic duct resulting from an anomaly in embryonic development. It is often linked with other congenital anomalies, but an isolated variant is very infrequent. Basic procedures/main findings:The clinical presentation is diverse. In fact, GA is often diagnosed incidentally. Magnetic resonance cholangiopancreatography (MRCP) is regarded as the preferred diagnostic approach, since it circumvents needless and risky surgical procedures in symptomatic patients. This report presents a case of gallbladder agenesis incidentally identified during surgery in a 29-year-old patient. Conclusions: Although GA is uncommon, clinical awareness of the disorder facilitates accurate preoperative diagnosis and thereby reduces morbidities associated with unnecessary surgical exploration.

The nonvisualization of the fetal gallbladder (NVFGB) is a rare finding, occurring in approximately 0.1% of pregnancies. The NVFGB may be classified as either isolated or nonisolated, depending on whether it occurs in conjunction with additional anomalies. A retrospective study, conducted from January 2016 to May 2022 was designed to evaluate the clinical features, management and prognosis of NVFGB. Thirteen cases were referred to the prenatal diagnostic center. The cases were classified as two that were isolated and 11 were nonisolated. In isolated cases, chromosomal analysis and genetic testing for common CFTR (cystic fibrosis transmembrane conductance regulator) mutations yielded normal results, and isolated gallbladder agenesis was confirmed postnatally. In the nonisolated group, two cases were diagnosed with cystic fibrosis (CF) and one with Williams syndrome. Of the 11 nonisolated cases, ten resulted in termination of pregnancy (TOP), while in one case, the gallbladder was observed at 24-week gestation. Prenatal management of NVFGB remains a significant challenge. Its prognosis is closely related to the presence of other abnormalities. CF plays a significant role when gastrointestinal anomalies are detected. When isolated, once CF and chromosomal abnormalities are excluded, NVFGB is generally considered a benign condition.

Heterozygotic GATA6 mutations are responsible for various congenital diseases in the heart, pancreas, liver, and other organs in humans. However, there is lack of an animal that can comprehensively model these diseases since GATA6 is essential for early embryogenesis. Here, we report the establishment of a gata6 knockout zebrafish which recapitulates most of the symptoms in patients with GATA6 mutations, including cardiac outflow tract defects, pancreatic hypoplasia/agenesis, gallbladder agenesis, and various liver diseases. Particularly in the liver, the zebrafish gata6 model exhibits the paucity of intrahepatic bile ducts, disrupted bile canaliculi, cholestasis, resembling the liver diseases associated with GATA6 mutations. Moreover, an unreported phenotype, hepatic cysts, has been also revealed in the model. Mechanistically, Gata6 interacts with Hhex and binds lrh-1 promoter to synergistically activate its expression, thereby enhancing the Lrh-1-mediated β-catenin signaling which is essential for liver development. This transcriptional activation of lrh-1 is tightly controlled by the negative feedback, in which Lrh1 interacts with Gata6 to weaken its transactivation ability. Moreover, Gata6 level is regulated by Hhex-mediated proteasomal degradation. The orchestration by these three transcription factors precisely modulates Gata6 activity, ensuring β-catenin signaling output and proper liver development in zebrafish. Importantly, the molecular mechanism identified in zebrafish is conserved in human cells. GATA6 mutant variants associated with hepatobiliary malformations in humans interact aberrantly with HHEX, resulting in subsequent impairments of LRH-1 activation. Conclusively, the disease model established here provides both phenotypic and mechanism insights into the human hepatic diseases associated with GATA6 mutations.

The objective of this study was to investigate the ultrasonographic characteristics and outcomes of fetuses with atypical and non-visualized fetal gallbladder in our tertiary care hospital. A retrospective analysis was conducted on cases in which the fetal gallbladder was not visualized or exhibited atypical characteristics at our institution over a four-year period. The patients were divided into two groups: absent gallbladder and atypical gallbladder. The groups with isolated and additional anomalies were analyzed according to their ante- and postnatal characteristics. The study comprised 78 patients (37 absent, 41 atypical gallbladder). In the isolated fetal absence of gallbladder group, the gallbladder was visualized in three of 13 patients during antenatal ultrasonographic follow-up and in half of the remaining 10 patients during postnatal follow-up. In the postnatal period, five newborns with absent isolated gallbladder are being followed up with suspicion of biliary atresia and isolated gallbladder agenesis. In the absence of a gallbladder with an additional anomaly group, 58% of fetuses died during the intrauterine and neonatal period. Fetuses in the isolated atypical gallbladder group are being followed as healthy after birth. Pregnancies with atypical gallbladder appearance and additional anomalies resulted in 33% neonatal death, 12% intrauterine demise, and 25% termination of pregnancy. In instances where the fetal gallbladder is not consistently discernible, it is imperative to exercise caution with regard to the possibility of biliary atresia. In the event that the fetal gallbladder exhibits unusual characteristics, a meticulous examination for the presence of additional anomalies is recommended.

Agenesis of the gallbladder is a rare congenital anomaly. The aim of this study is to explore, through the case we present, the epidemiological aspects of this anomaly as well as the specificities of diagnosis and therapeutic management. The patient is a 35-year-old individual with no significant medical history, who presented with hepatic colic and an ultrasound showing a sclerotic and atrophic gallbladder. A laparoscopic cholecystectomy was indicated. Intraoperatively, the gallbladder was not visualized, even after examining various ectopic sites for the gallbladder.