Diagnosis Of GS Research Articles

NCMP-16. A CASE OF WIDESPREAD EXTRACRANIAL METASTASES FROM A GLIOSARCOMA

Abstract BACKGROUND: Glioblastoma (GBM) with sarcomatous features (gliosarcoma) accounts for 2-8% of all glioblastomas1,2, characterized by a biphasic histopathology pattern consisting of glial and sarcomatous components. While GBMs generally do not metastasize outside the central nervous system (CNS), GS has been associated with extracranial metastases in up to 11% of cases3. Case presentation: A 58-year-old right-handed woman with a GBM presented to our institution for a second opinion. She was initially diagnosed 18 months prior and had received radiotherapy with concurrent temozolomide. Her adjuvant temozolomide was discontinued due to rash, and she started on bevacizumab. Her tumor progressed and she sought additional treatment options. On her initial presentation, she was tachycardic with leukocytosis, prompting admission. A chest CT showed thoracic adenopathy, multiple bilateral pulmonary nodules, and a large left malignant pleural effusion. Bronchoscopy revealed spindle cell sarcomatoid neoplasm raising the possibility of metastasis from a CNS primary tumor. Additionally, the patient endorsed development of subacute radicular pain in her bilateral lower extremities as well as weakness. MRI of total spine revealed multilevel osseous and epidural lesions, infiltrating the paraspinal muscles and thickening of cauda roots with concern for leptomeningeal disease. A subsequent PET-CT showed increased FDG avidity in these lesions. Reevaluation of the initial CNS pathology confirmed the presence of mesenchymal/sarcomatous differentiation, consistent with a diagnosis of GS. As confirmed by autopsy, the patient eventually passed away due to widespread and metastatic disease. Discussion: While GBM rarely metastasizes outside the CNS, GBM with sarcomatous features are more likely to exhibit extracranial metastasis. Our patient had widespread involvement, including the lungs, heart, liver, omentum, and bone. Metastasis was thought most likely once EBUS of the lung returned with sarcomatous features. Clinicians should therefore maintain a high suspicion for metastases when dealing with patients diagnosed with GS.

Clinical and survival characteristics of primary and secondary gliosarcoma patients

PurposeGliosarcoma (GS) is classified by the World Health Organization as a subtype of glioblastoma with sarcomatous features. GS have a propensity to metastasize, as opposed to other gliomas, with lower 5-year survival rates than GBM patients. In this study, we identified differences in survival between patients with primary and secondary GS. MethodsWe retrospectively identified patients who presented at the MD Anderson Cancer Center with a pathology-confirmed diagnosis of GS. We defined overall survival (OS) from the date of pathological diagnosis of primary GS (from sarcomatous change for secondary GS). We defined progression-free survival (PFS) from the date of GS chemoradiation completion to radiographic disease progression. We used Kaplan-Meier survival estimates and the log-rank test to compare OS and PFS between primary and secondary GS. We used univariable Cox proportional hazard regression to assess differences in OS & PFS by various characteristics. ResultsWe identified 94 GS patients; 70 had primary disease and 24 secondary. Molecular analysis of GS tumor samples revealed that 47.1% were GFAP positive, 38.5% S-100 positive, and 83.7% reticulin-positive. Among the tested samples, 3.8% had IDH and 73.1% had TP53 mutations. The median OS for all patients was 16.8 months. Median OS from the pathological diagnosis of GS was 17.3 months for primary and 10.2 months for secondary GS. Median OS for secondary GS was 28.9 months from initial diagnosis of the primary neoplasm. ConclusionsOur study is the largest single institution evaluation of GS and provides insight into patterns of survival for GS.

Inflammatory arthritis complicating galactosialidosis: a case report

BackgroundGalactosialidosis (GS) is a rare inherited lysosomal storage disorder (LSD) which is characterized by a defect in the lysosomal glycoprotein catabolism. We report, for the first time, the case of a child affected by GS presenting with recurrent episodes of extensive joint inflammation in both knee joints. The aim of this case-report is to describe the clinical presentation as well as the laboratory, radiologic and microscopic features of this unique presentation of GS. Furthermore, we explore inflammatory mechanisms potentially responsible for the origination of the arthritic joint pathology observed in our patient.Case presentationWe describe the rare case of a 12-year-old boy diagnosed with GS (late infantile form) who presented with multiple episodes of inflammatory arthritis involving both knees; no other joints were suspected for joint inflammation. Laboratory results did not indicate an autoimmune disorder. Synovial fluid tested negative for any bacterial infection and ruled out a malignancy and crystal-induced arthritis. Microscopic examination of the synovial tissue revealed numerous foamy macrophages with extensive vacuolization, consistent with the previous diagnosis of GS. Treatment consisted of aspiration of excessive joint fluid and subsequent intra-articular injection of triamcinolonhexacetonide with excellent but transient result. Given the evidence of storage products within macrophages of the inflamed synovial tissue and the absence of other etiological clues, GS itself was considered as the primary cause for the relapsing inflammatory joint pathology. According to the restricted data on articular manifestations in GS, to date, GS cannot be linked directly to joint inflammation. Nevertheless, in several other LSDs, the accumulation of storage material has been associated with numerous osteoimmunological changes that might play a role in the pathophysiology of arthritic processes.ConclusionsWe hypothesize that the articular build-up of GS storage products triggered systemic as well as local inflammatory processes, resulting in the extensive inflammatory joint pathology as observed in our patient. Future identification of other patients with GS is required to corroborate the existence of an arthritic clinical phenotype of GS and to assess the underlying pathophysiology.

Variable clinical characteristics and laboratory results in five patients with Chinese Good's syndrome (thymoma and hypogammaglobulinemia): an 8-year retrospective analysis in a university hospital in China

BackgroundGood's syndrome (GS) is a rare secondary immunodeficiency disease presenting as thymoma and hypogammaglobulinemia. Due to its rarity, the diagnosis of GS is often missed.MethodsWe used the hospital information system to retrospectively screen thymoma and hypogammaglobulinemia patients at the First Affiliated Hospital of Wenzhou Medical University from Apr 2012 to Apr 2020. The clinical, laboratory, treatment, and outcome data for these patients were collected and analyzed.ResultsAmong the 181 screened thymoma patients, 5 thymoma patients with hypogammaglobulinemia were identified; 3 patients had confirmed diagnoses of GS, and the other 2 did not have a diagnosis of GS recorded in the hospital information system. A retrospective review of the clinical characteristics, laboratory results, and follow-up data for these 2 undiagnosed patients confirmed the diagnosis of GS. All 5 GS patients presented with pneumonia, 2 patients presented with recurrent skin abscesses, 2 patients presented with recurrent cough and expectoration, 1 patient presented with recurrent oral lichen planus and diarrhea, and 1 patient presented with tuberculosis and granulomatous epididymitis. In the years after the diagnosis of hypogammaglobulinemia with mild symptoms, all 5 patients had received irregular intravenous immunoglobulin (IVIG) treatment. As the course of the disease progressed, the clinical symptoms of all patients worsened, but the symptoms were partly resolved with IVIG in these patients. However, 4 patients died due to comorbidities.ConclusionGS should be investigated as a possible diagnosis in thymoma patients who present with hypogammaglobulinemia, especially those with recurrent opportunistic infections, recurrent skin abscesses, chronic diarrhea, or recurrent lichen planus.

Clinical and Genetic Features in 31 Serial Chinese Children With Gitelman Syndrome.

Gitelman syndrome (GS, OMIM 263800) is a genetic congenital tubulopathy associated with salt loss, which is characterized by hypokalemic metabolic toxicity, hypocalciuria, and hypomagnesemia. GS, which is typically detected in adolescence or adulthood, has long been considered a benign tubular lesion; however, the disease is associated with a significant decrease in the quality of life. In this study, we assessed the genotype–phenotype correlations based on the medical histories, clinical symptoms, laboratory test results, and whole-exome sequencing profiles from pediatric patients with GS. Between January 2014 and December 2020, all 31 consecutively enrolled patients complained of fatigue, salt craving, and muscle weakness. Sixteen patients demonstrated growth retardation, and five patients presented with nocturia and constipation. All patients presented with hypokalemic metabolic alkalosis, normal blood pressure, hyperaldosteronism, and a preserved glomerular filtration rate, and 24 of the 31 (77.4%) patients had hypomagnesemia. Homozygous, compound heterozygous, and heterozygous mutations in SLC12A3 were detected in 4, 24, and 3 patients, respectively. GS patients often present with muscle weakness and fatigue caused by hypokalemia and hypomagnesemia. Therefore, early diagnosis of GS is important in young children to reduce the possibility of growth retardation, tetany, and seizures. Next-generation sequencing such as whole-exome or whole-genome sequencing provides a practical tool for the early diagnosis and improvement of GS prognosis. Further whole-genome sequencing is expected to reveal more variants in SLC123A among GS patients with single heterozygous mutations.

Recurrence of Goodpasture syndrome without circulating anti-glomerular basement membrane antibodies after kidney transplant, a case report

BackgroundGoodpasture Syndrome (GS) is an autoimmune disease caused by the development of auto-antibodies against the Glomerular Basement Membrane (GBM). Linear deposit of immunoglobulins G on the GBM detected by immunofluorescence analysis of renal biopsies is a GS pathognomonic finding. GS is commonly monophasic and its incidence is 1.6 case per million per year.Case presentationThis report describes and discusses the case of a 40-year-old woman who one year after allograft kidney transplant, presented with acute pulmonary and renal symptoms of GS, leading to acute graft dysfunction, without circulating anti-GBM antibody detection in laboratory assays. She received a living donor kidney transplant 4 years after the first diagnosis of GS without circulating anti-GBM antibodies, when considered in remission.ConclusionsIn both episodes, the diagnosis of GS was based exclusively on the kidney biopsy that showed rapidly progressing glomerulonephritis with deposition of immunoglobulins G on the GBM. Although rare, the management of patients with GS without circulating anti-GBM antibodies is difficult due to the lack of standardized follow-up guidelines to reduce the risk of GS recurrence after kidney transplantation.

Spectral Computed Tomography Imaging of Gastric Schwannoma and Gastric Stromal Tumor.

Patients diagnosed with GS or GST at Lanzhou University Second Hospital, China, between May 2013 and June 2015 were included retrospectively. The subjects underwent spectral CT examination before surgery and had histologically confirmed diagnosis of GS or GST. Twelve patients with GS (3 men; 9 women; mean [SD] age, 47.0 [11.5] years) and 20 with GST (7 men; 13 women; mean [SD] age, 54.7 [9.9]) showed significant differences in terms of arterial phase (AP) at 70 keV (P < 0.001), portal phase (PP) at 70 keV (P = 0.002), AP iodine concentration, PP iodine concentration, AP water concentration, AP slope of spectral curve, and PP slope of spectral curve (all P < 0.001). Spectral CT may be useful for noninvasive diagnosis of submucosal tumors.

Gitelman syndrome in a South African family presenting with hypokalaemia and unusual food cravings

BackgroundGitelman syndrome (GS) is an autosomal recessive renal tubular disorder characterised by renal salt wasting with hypokalaemia, metabolic alkalosis, hypomagnesaemia and hypocalciuria. It is caused by mutations in SLC12A3 encoding the sodium-chloride cotransporter on the apical membrane of the distal convoluted tubule. We report a South African family with five affected individuals presenting with hypokalaemia and unusual food cravings.MethodsThe affected individuals and two unaffected first degree relatives were enrolled into the study. Phenotypes were evaluated through history, physical examination and biochemical analysis of blood and urine. Mutation screening was performed by sequencing of SLC12A3, and determining the allele frequencies of the sequence variants found in this family in 117 ethnically matched controls.ResultsThe index patient, her sister, father and two aunts had a history of severe salt cravings, fatigue and tetanic episodes, leading to consumption of large quantities of salt and vinegar. All affected individuals demonstrated hypokalaemia with renal potassium wasting. Genetic analysis revealed that the pseudo-dominant pattern of inheritance was due to compound heterozygosity with two novel mutations: a S546G substitution in exon 13, and insertion of AGCCCC at c.1930 in exon 16. These variants were present in the five affected individuals, but only one variant each in the unaffected family members. Neither variant was found in any of the controls.ConclusionsThe diagnosis of GS was established in five members of a South African family through clinical assessment, biochemical analysis and mutation screening of the SLC12A3 gene, which identified two novel putative pathogenic mutations.

Granulocytic Sarcoma, A Single-Institution Survey of Clinical Presentation and Trajectory

AbstractAbstract 1041▪▪This icon denotes a clinically relevant abstract IntroductionGranulocytic Sarcoma (GS), also known as chloroma or myeloblastoma, is a rare neoplasm composed of immature myeloid cells occurring in any extramedullary organ, most commonly in the lymph node and soft tissue. It can occur as an isolated lesion, or in conjunction with a diagnosis of acute myeloid leukemia (AML), myeloproliferative disorder (MPD) or myelodysplastic syndrome (MDS). GS has been generally associated with more aggressive disease and a poor prognosis. Although it has been described in the literature in small case series, the clinical characteristics and prognosis of patients with GS associated with AML, MDS, MPD or as an isolated lesion have not been thoroughly described. We therefore studied our institutional experience of granulocytic sarcoma to gain further insight into the clinical features and associations of this disease. MethodsWe conducted a retrospective medical record review of patients who presented with GS to Massachusetts General Hospital from 1994 through 2011. In total, 35 patients with GS were identified. Kaplan Meier method was used to estimate overall survival (OS). OS was defined as the duration from the time of diagnosis of GS to date of death; patients still alive at the time of analysis were censored. Patients were categorized into three groups for analysis depending on the presence of bone marrow disease: primary (isolated) GS, GS associated with AML, and GS associated with MDS or MPD. ResultOf 35 patients with GS, 20 (57%) were associated with a diagnosis of AML, 10 (29%) presented with either MDS or MPD, and 5 (14%) presented with primary GS. Of the AML-associated GS, 13 occurred concurrently with AML at diagnosis and 7 presented as AML relapse. Of the 10 cases of GS with either MDS or MPD, one patient presented with MDS and 9 with MPD. The median age of all patients was 57 years old; 19 of 35 patients were female. Median white blood count (WBC) was 4.6 (th/cmm) (IQR 3.5–8.8) for patients with AML-associated GS and 20.2 (th/cmm) (IQR 9.7–61) for those with MDS/MPD-associated GS. One year survival was 10% (95% CI 0.5 – 35.8%) in MDS/MPD associated GS, 49.5% (95% CI 26.5 – 68.9%) in AML associated GS, and 60% (95% CI 12.6 to 88.2%) in primary GS. The most common area of involvement in patients with AML-associated GS was the nervous system (22%). In contrast, among patients with MPD/MDS-associated GS, the most commonly involved site was bone (45%) (Table 1). 63% of all patients had one site of involvement with GS at presentation. The most common presenting symptom was pain either caused by a mass or lymphadenopathy. Cytogenetics were normal for the majority of patients. Interestingly, however, one AML patient and one patient with primary GS presented with a 9;22 translocation, two AML presented with other cytogenetic abnormalities involving chromosome 9 (t(9;11)(p22;q23) & add(9)(q34)), and three others, including one with primary GS, displayed abnormalities at chromosome 11, specifically 11q23 (Table 2). ConclusionsWith this study, we provide a single institution experience of granulocytic sarcoma, a rare manifestation of myeloid neoplasms. Interestingly, we found variable presentation with different patterns of site involvement and white blood counts in patients with GS associated with AML and in those with GS associated with MPD/MDS. Additionally, certain karyotypic abnormalities were over-represented in patients with GS, including t(9;22) and translocations involving chromosome 11q23. Finally, in our small series, patients with a diagnosis of GS associated with MPD/MDS had worsened outcomes compared to those with AML-associated GS or primary GS. Larger, prospective studies are needed to better and more fully assess outcomes in these patients.Table 1:Sites of GSSites of GSPrimary GSGS associated with AMLGS associated with MDS/MPDNervous system (not CNS leukemia)154Lymph node41Soft tissue/skin232Orbit3Testes2Abdominal viscera121Bone25Submandibular gland1Oral cavity1Table 2:Cytogenetic abnormalities in patients with GSChromosomal abnormalitiesPrimary GSGS with AMLMDS/MPDNormal171t(3;22)(p25;q13)1t(9;22)(q34;q11)114t(9;11)(p22;q23)1add(9)(q34)111q231del(16)1t(8;21)(q22;q22)2Complex21t(11;17)(q23;q21)15q deletion1t(15,17)1Not available125 Disclosures:No relevant conflicts of interest to declare.

Granulocytic sarcoma of the pancreas: A case report and review of the literatures

BackgroundGranulocytic sarcoma (GS) is a form of acute myeloid leukemia (AML), also known as extramedullary myeloid tumor or chloroma. It forms a solid malignant tumor consisting of myelocytes or granulocytes and is typically located in bone while occurrence in other parts of the body is rare.Case presentationWe reported a 40-year-old male patient who had jaundice, highly elevated bilirubin, and a mass highly suspicious of pancreatic head carcinoma. We performed surgery and the pathology and immunohistochemistry suggested GS; however the blood test and the bone marrow infiltration showed no evidence of AML. In our review of the published reports of GS, we only found six reports of the GS in the pancreas, and we suggested that immunohistochemical staining should be used to accurately differentiate GS from other pancreatic cancer and other types of leukemia.ConclusionsThe accurate diagnosis of GS is necessary for determining prognosis and deciding appropriate therapy.

Phenobarbital for Long-Term Management of Marked Hyperbilirubinemia.

Abstract 5089 Gilbert's syndrome (GS) is associated with a mild chronic unconjugated hyperbilirubinemia, due to partial deficiency of bilirubin uridine diphosphate glucuronyl transferase (UDPGT). Phenobarbital is a known inducer of hepatic UDPGT and has been used in hyperbilirubinemia of newborns. It has also been used as a test for support of the diagnosis of GS. However, because hyperbilirubinemia of GS is mild and harmless, phenobarbital is not used for treatment of hyperbilirubinemia in adults. I report a case of a 46-year-old woman who, because of having chronic hereditary hemolytic anemia and GS, had marked hyperbilirubinemia with psychosocial problems, as the result of her hyperbilirubinemia and her skin color, which responded well to chronic phenobarbital treatment. Case report- CH was diagnosed to have hereditary high phosphatidylcholine hemolytic anemia (HHPCHA) at the age of 23. She was seen again at the age of 30 because of very high serum ferritin and iron saturation which seemed disproportionally high for the degree of her mild hemolytic anemia (51Cr RBC survival T½ of 16.5 days). Further investigation revealed that she had hereditary hemochromatosis due to homozygosity for H63D HFE gene. She was started on phlebotomies initially weekly and later on every 2-3 months to control her iron overload. During the follow-up it was noted that her serum unconjugated bilirubin (SUB) was persistently much higher than is expected from her mild hemolytic anemia (up to 288 μmol/L). Since she had no abnormality of liver function tests, I suspected that she also has Gilbert's syndrome. In September 2008 her blood was sent for genetic testing which showed that she has an additional TA repeat [(TA)7/(TA)7], confirming the diagnosis of GS. On January 21, 2009 when her SUB was 149 μmol/L, she expressed concern that her friends and coworkers keep making fun of her, because of the orange color of her face and sclera. She was started on phenobarbital 30 mg daily for a month and then 60 mg daily. This therapy rapidly brought her bilirubin down and changed the color of her face to normal, making her very happy. Her SUB on February 20, March 20 and June 30, 2009 were 103, 63 and 37 μmol/L, respectively. Conclusion Gilbert's syndrome is a common hereditary disorder that can aggravate hyperbilirubinemia of chronic hemolytic anemia. However, this association is often unrecognized, because many physicians attribute the hyperbilirubinemia to hemolysis and do not look for associated GS. In chronic hemolytic anemias, if hyperbilirubinemia is more than expected, the possibility of an associated GS should be considered. If such association exists, small daily doses of phenobarbital can markedly reduce this hyperbilirubinemia and improve the psychosocial effects of hyperbilirubinemia. Furthermore, marked reduction of bilirubin, following the therapeutic trial of Phenobarbital, will confirm the association of GS with hemolytic anemia. Disclosures No relevant conflicts of interest to declare.

Delayed diagnosis of Gorlin's syndrome in a renal transplant recipient

A 35-year-old woman was referred to the dedicated dermatology clinic for RTR. She underwent her first renal transplant at 18 years of age due to chronic renal failure following reflux nephropathy of the single right kidney (left kidney agenesis). She has since then had two further transplants. During clinical examination she was noted to have at least 16 basal cell carcinomas (BCC) and there are records in the case notes of 10 BCC having being excised and confirmed histologically in the past. By contrast, she had only had two squamous cell carcinomas (SCC) excised. She was also noted to have distinctive facial features, a kyphoscoliosis and palmar pits, and a diagnosis of Gorlin's (naevoid BCC) syndrome (GS) was made. Although immunosuppression may have contributed to the multiplicity of her BCC, the contrasting very small number of SCC is unusual in an organ transplant recipient and this alerted the authors to the diagnosis of GS.

The Value of CD34, Myeloperoxidase and Chloracetate Esterase (Leder) Stain in the Diagnosis of Granulocytic Sarcoma

The differentiation of extramedullary myelogenous leukemia/granulocytic sarcoma (GS) from malignant lymphoma can sometimes be difficult. In the current study, we explored the value of CD34, myeloperoxidase and nonspecific esterase (Leder) stains in differentiating GS from lymphomas. Fifteen cases of phenotypically confirmed GS were stained for CD34, myeloperoxidase and Leder stains. The same stains were performed in 16 malignant lymphomas as controls. The GS cases were also immunostained for CD3 and CD20 to detect the incidence of aberrant T and B lymphocyte expression. CD34 was expressed in 7 of the 15 cases of GS (46%). Myeloperoxidase was expressed in 10 of the 15 cases (66%), and Leder stain was positive in 9 cases (60%). All 15 cases had expression of at least one marker; 8 cases had expression of two markers and one case had expression of all 3 markers. None of the lymphomas showed expression of any of the three markers. Five cases (35%) of GS showed T cell antigen expression and 2 (14%) showed B cell antigen expression. Our findings suggest that in cases of GS, the use of the combination of CD34, myeloperoxidase and Leder stains can help reach a definitive diagnosis, especially if lymphoma is difficult to exclude. Expression of B and T cell antigens in such lesions should not rule out the diagnosis of GS.

RIFAMPICIN TEST IN THE DIAGNOSIS OF GILBERT'S SYNDROME

SUMMARYGilbert's syndrome (GS) is characterised by the existence of chronic mild unconjugated hyperbilirubinaemia. The value of rifampicin as a provocative test for the diagnosis of GS was evaluated and compared with a fasting test. Twenty‐two patients with GS, 15 patients with chronic liver disease and 20 healthy controls were included. Both rifampicin and fasting tests were applied to all subjects. In the fasting test, the subjects were given a 400 calorie/day diet for 24 hours; in the rifampicin test, unconjugated bilirubin levels was measured before and four hours after taking 600 mg of rifampicin. Both tests achieved a significant increase in mean unconjugated bilirubin levels in patients with GS but not in the controls. The sensitivity and specificity of a rifampicin test in the diagnosis of GS were comparable with the fasting test. However, both tests caused a significant increase in unconjugated bilirubin levels in nearly half the patients with chronic liver disease. A rifampicin test may be used in the diagnosis of suspected GS instead of a fasting test, as it is simpler and more practical. However, its specificity for GS is not sufficient, because it also causes an increase in unconjugated bilirubin levels in some patients with chronic liver disease.

Unusual early presentation of Gilbert syndrome in pediatric recipients of liver transplantation.

Gilbert syndrome as a rule becomes manifest in adolescence or in early adulthood; it may be transferred by the donor to orthotopic liver transplant (OLT) recipients. We examined the frequency of Gilbert syndrome in 46 OLT pediatric recipients who had a follow-up of 1 year or more. Diagnostic criteria included unexplained chronic or recurrent unconjugated hyperbilirubinemia; its increase after reduced caloric intake plus prolonged fasting, without changes of the proportion of conjugated bilirubin; and high relative amounts of serum unconjugated bilirubin IXa and prevalence of the monoglucuronide over the diglucuronide. Of the 46 patients, 42 had normal bilirubin values. Only four otherwise healthy OLT recipients showed hyperbilirubinemia and normal conjugated fractions. Liver donors had been four men. Hyperbilirubinemia persisted with a fluctuating pattern for the whole follow-up after OLT in all. Total bilirubin level in blood samples obtained after reduced caloric intake and prolonged fasting became notably higher than basal values, whereas the proportion of conjugated bilirubin remained stable. High relative amounts of unconjugated bilirubin IXa and prevalence of the monoglucuronide over the diglucuronide were found. Finally, DNA from liver donors' lymphocytes was available for one jaundiced and two nonjaundiced patients: tests for abnormalities in the promoter region of the gene for the enzyme bilirubin uridine diphospho-glucuronosyltransferase were in agreement with a diagnosis of GS in the former one, Gilbert syndrome may have an unusual early presentation in pediatric OLT recipients.

Unusual Early Presentation of Gilbert Syndrome in Pediatric Recipients of Liver Transplantation

ABSTRACTBackgroundGilbert syndrome as a rule becomes manifest in adolescence or in early adulthood; it may be transferred by the donor to orthotopic liver transplant (OLT) recipients.MethodsWe examined the frequency of Gilbert syndrome in 46 OLT pediatric recipients who had a follow‐up of 1 year or more. Diagnostic criteria included unexplained chronic or recurrent unconjugated hyperbilirubinemia; its increase after reduced caloric intake plus prolonged fasting, without changes of the proportion of conjugated bilirubin; and high relative amounts of serum unconjugated bilirubin IXa and prevalence of the monoglucuronide over the diglucuronide.ResultsOf the 46 patients, 42 had normal bilirubin values. Only four otherwise healthy OLT recipients showed hyperbilirubinemia and normal conjugated fractions. Liver donors had been four men. Hyperbilirubinemia persisted with a fluctuating pattern for the whole follow‐up after OLT in all. Total bilirubin level in blood samples obtained after reduced caloric intake and prolonged fasting became notably higher than basal values, whereas the proportion of conjugated bilirubin remained stable. High relative amounts of unconjugated bilirubin IXa and prevalence of the monoglucuronide over the diglucuronide were found. Finally, DNA from liver donors' lymphocytes was available for one jaundiced and two nonjaundiced patients: tests for abnormalities in the promoter region of the gene for the enzyme bilirubin uridine diphospho‐glucuronosyltransferase were in agreement with a diagnosis of GS in the former one.ConclusionsGilbert syndrome may have an unusual early presentation in pediatric OLT recipients.