Gilbert's Syndrome Research Articles

S2157 Vibrio Species Infection Followed by New Onset Lymphocytic Colitis: Cause or Coincidence?

Introduction: The pathophysiology and epidemiology of lymphocytic colitis (LC), a form of microscopic colitis, is not well understood. The incidence of this disorder in some populations has increased over time, nearing that of inflammatory bowel disease (IBD). Medications, autoimmune conditions, infectious etiologies, and genetics have been proposed as predisposing to or triggering LC. Of the reported bacterial pathogens, Vibrio species has not yet been linked to LC. We report a case of LC diagnosed post-infection with Vibrio spp. Case Description/Methods: A 68-year-old male with a past medical history of Gilbert syndrome, remote tobacco use, GERD, anxiety and hyperlipidemia presented with 8-12 episodes daily of watery diarrhea for 16 days. The diarrhea, associated with fecal incontinence and abdominal cramping, began after consumption of raw clams and oysters. The patient’s abdominal exam was without tenderness to palpation, masses, or organomegaly. Initial labs showed no leukocytosis and electrolytes were normal. Stool studies demonstrated a positive fecal leukocyte stain. A stool PCR was positive for Vibrio cholerae/parahaemolyticus. He was treated with tetracycline, though his symptoms did not completely relent. Repeat stool cultures were negative despite residual loose stools. Further workup included a negative stool C. Diff toxin and excluded celiac disease. Postinfectious IBD was suspected, and he was started on a FODMAP diet and dicyclomine. Despite reported compliance, his symptoms did not improve. Subsequent colonoscopy revealed a grossly normal ileum and colon. Colonic biopsies depicted colonic mucosa with mildly increased intraepithelial lymphocytes, consistent with LC. Treatment was initiated with oral budesonide and tapered. Diarrhea resolved after 2 weeks of treatment. Discussion: The temporal nature of Vibrio spp. infection raises the question of causality of LC. H. Pylori, Yersinia, and C. Diff have been linked to collagenous colitis. Thus far, LC has only been linked to Campylobacter jejuni. Statins, PPIs, and SSRIs have also been associated with LC. PPI use may predispose to Vibrio infection due to hypochlorhydria. Consideration of post-infectious IBD and new onset LC raises an interesting point, as the conditions are clinically similar. While the exact mechanism of post-infectious LC is unknown, upregulation of nitric oxide synthase is seen in both infection with Vibrio and LC. Further metabolic clarification and investigation are yet required to define the pathogenesis of this disorder.

Complex Sources of Hyperbilirubinemia

The authors present a case of a patient with severe hyperbilirubinemia due to acute hepatitis B infection which resolved without intervention with subsequent normalization of synthetic and excretory liver function. Despite this, the patient remained jaundiced due to unconjugated hyperbilirubinemia in the context of a recent diagnosis and flare of hereditary spherocytosis. Due to the complex clinical presentation, the patient underwent a liver biopsy with the additional genetic diagnosis of Gilbert’s Syndrome being established. This illustrates an unusual case of both Hepatitis B and hereditary spherocytosis being a potential cause for a flare of Gilbert Syndrome.

Slow increase of bilirubin concentration during administration of lenalidomide, bortezomib and dexamethasone for multiple myeloma (unmasking previously undiagnosed Gilbert syndrome) and disappearance of necrobio­tic xanthogranuloma after complete remission of multiple myeloma

Lenalidomid ranks among immunomodulatory drugs. There are a few of the more common side effects, like a higher risk of venous trombembolism or diarrhea. Other side effects are rare. The hyperbilirubinemia described in this article can be assigned to them. In our case, the increase of bilirubin was associated with unrecognized Gilbert syndrome. We report a patient with multiple myeloma and necrobio-tic xanthogranuloma (NXG) of the skin and liver. After the treatment with bortezomib, lenalidomid and dexamethasone, complete remission was attained after 4 cycles with decrease of monoclonal immunoglobulin to an unmeasurable concentration. At the same time, the dis-appearance of cutaneous and hepatic lesions of NXG on FDG-PET/CT was evident. The administration of bortezomib was stopped after 8 cycles and only continued with lenalidomide as a maintenance therapy. However, after four cycles of this therapy, bilirubin increased above the upper limit and the increase continued till the 11th month of lenadomide administration, when bilirubin reached the highest concentration of 75 μmol/l (more than the three-fold of the upper limit, grade III toxicity). The patient had asymptomatic hyperbilirubinemia with no underlying liver disease or renal impairment while being on lenalidomide therapy. Genetic studies proved mutation; insertion in the promotor gene UGT1A1 typical for Gilbert syndrome. Hyperbilirubinemia may be attributed to the unmasking of previously undia-gnosed Gilbert syndrome. Therefore, the therapy with lenalidomide was interrupted after 11 months. The bilirubin level decreased after the discontinuation of the drug. NXG disappeared after fulfilling complete remission of multiple myeloma with disappearance of monoclonal immunoglobulin. This observation supports the hypothesis that monoclonal immunoglobulin has a crucial role in the ethiopathogenesis of NXG and suggests the treatment of monoclonal gammopathy if present in a patient with NXG, hoping that this will result in xantogranuloma disappearance.

Bilirubin metabolism and UDP-glucuronosyltransferase 1A1 variants in Asians: Pathogenic implications and therapeutic response.

In the Asian general population, at least six single-nucleotide variants (SNVs) in the UDP-glucuronosyltransferase (UGT) 1A1 gene have been identified: -3279T>G, -53A(TA)6 TAA>A(TA)7 TAA, 211G>A, 686C>A, 1091C>T, and 1456T>G. Each of these six SNVs was observed in at least four ethnic groups of the 12 Asian populations studied. In East Asian populations, the descending frequency of these six SNVs was as follows: -3279G>[-53A(TA)7 TAA, 211A]>(686A, 1091T)>1456G. Because of the presence of linkage disequilibrium and the expulsion phenomenon, when the SNVs -3279G, -53A(TA)7 TAA, 211A, and 686A were simultaneously involved, 15 instead of the estimated 81 genotypes were observed. Those carrying 686AA or 1456GG developed Gilbert's syndrome or Crigler-Najjar syndrome type 2. Both -53A(TA)7 TAA/A(TA)7 TAA and 211AA are the main causes of Gilbert's syndrome in East Asian populations. In East Asian populations, the 211AA genotype is the main cause of neonatal hyperbilirubinemia, whereas -53A(TA)7 TAA/A(TA)7 TAA exerts a protective effect on hyperbilirubinemia development in neonates fed with breast milk. Both 211A and -53A(TA)7 TAA are significantly associated with adverse drug reactions induced by irinotecan (one of the most widely used anticancer agents) in Asians. However, at least three common SNVs (-3279G, -53A(TA)7 TAA, and 211A) should be comprehensively analyzed. This study investigated the clinical significance of these six SNVs and demonstrated that examining UGT1A1 variants in Asian populations is considerably challenging.

Serum Bilirubin Concentrations and the Prevalence of Gilbert Syndrome in Elite Athletes

ObjectivesBilirubin is a potent endogenous antioxidant and immunomodulating substance, which is also implicated in both cell signalling and various metabolic pathways. Mild elevation of systemic bilirubin concentrations provides substantial protection against many diseases of civilization. Rare published reports have suggested that serum bilirubin might also be relevant to sports performance. The purpose of the current study was to evaluate serum bilirubin concentrations and the prevalence of Gilbert syndrome (GS) in elite athletes.MethodsThe study was carried out in 536 consecutive healthy elite athletes and in 2594 individuals of the Czech post-MONICA study representing the general Czech population. Serum bilirubin concentrations, the prevalence of benign hyperbilirubinemia > 17 µmol/L (1 mg/dL, a phenotypic sign of GS), and a variant of the UGT1A1 gene promoter responsible for GS manifestation in Caucasians (rs81753472) were evaluated in study subjects.ResultsCompared to the general Czech population, significantly higher serum bilirubin concentrations were found in elite athletes (9.6 vs. 11.6 µmol/L, p < 0.001), both in men (11.3 vs. 12.6 µmol/L, p < 0.001) and women (8.3 vs. 10.5 µmol/L, p < 0.001). Furthermore, the prevalence of GS was also significantly higher in elite athletes (9.6 vs. 22%, p < 0.001) together with the tendency to higher frequencies of the genotypes (TA)7/7 and (TA)6/7UGT1A1.ConclusionElite athletes have significantly higher concentrations of serum bilirubin, the most potent endogenous antioxidant substance known. Simultaneously, the prevalence of GS syndrome is also much higher in elite athletes, suggesting that a mild elevation of serum bilirubin might predispose to better sports performance.

Gilbert Syndrome and Genetic Findings in Children: A Tertiary-Center Experience from Turkey.

ObjectiveGilbert syndrome (GS) is a disease characterized by mildly elevated indirect serum bilirubin levels due to mutation in the promoter of the UGT1A1 gene, which causes a decrease in uridine diphosphate glucuronyltransferase enzyme activity. Gilbert syndrome should be considered based on clinical and laboratory findings in differential diagnosis, which can be supported by genetic analysis. This study aimed to evaluate the clinical findings and UGT1A1 mutations of children with Gilbert syndrome.Materials and MethodsPatients who were admitted to the pediatric gastroenterology clinic and who were considered to have Gilbert syndrome based on clinical and laboratory findings were included in the study. The UGT1A1 analysis was performed by Sanger sequence analysis.ResultsA total of 56 children were included in the study. A(TA)7TAA, A(TA)6TAA, and (TA)6/7 allele promoter polymorphism was detected in 75.5%, 22.5%, and 2% of the patients, respectively. Other than these, in 3 patients, 3 different sequence variants associated with GS [c.880_893delinsA (p.Tyr294MetfsTer69) and c.1091C>T(p.Pro365Leu)] were detected.ConclusionWe detected 7 TA repeats in the majority of our patients. A mild bilirubin elevation was determined in cases with 6 repetitions that were not considered risky for Gilbert syndrome. We concluded that the c.880_893delinsA (p.Tyr294MetfsTer69) variant, previously shown to be associated with Crigler–Najjar syndrome type I, may also be associated with partial enzyme deficiency leading to the Gilbert syndrome phenotype.

Aortic Valve Replacement in a Juvenil Patient with Gilbert Syndrome and Hyperlipidemia

Gilbert Sendromu, bilirubinin kandan hepatositlere anormal şekilde up-take edilişi nedenli indirekt bilirubin düzeyinde ondülan yükselme görülmesidir. Aort darlığı, hiperlipidemi ve Gilbert Sendromu tanılı 16 yaşındaki erkek hastada kardiyopulmoner bypass eşliğinde yapılan mekanik aort kapak replasmanı, erken ve orta dönem postoperatif bulguları sunmaktayız.

Gilbert or Crigler\u2013Najjar syndrome? Neonatal severe unconjugated hyperbilirubinemia with P364L UGT1A1 homozygosity

BackgroundSeveral mutations of bilirubin uridine diphosphate-glucuronosyltransferase gene (UGT1A1) have been reported in patients with unconjugated hyperbilirubinemia. Few reports are available about the p.Pro364Leu mutation (P364L, c.1091C > T) in homozygous newborns. We describe the clinical, laboratory and therapeutic approach in two Chinese neonates with severe jaundice, homozygous for the P364L mutation.Case presentationTwo Chinese breastfed female infants presented prolonged unconjugated hyperbilirubinemia at the age of 1 month. Total bilirubin was higher than 15 mg/dl (D < 1). An exhaustive etiological work-up to detect possible causes of hyperbilirubinemia (notably hemolytic ones) was negative.The promoter and coding regions of UGT1A1 were amplified by polymerase chain reaction (PCR) from genomic DNA isolated from leukocytes. Both patients resulted homozygous for a variant site within the coding region of the gene in the 4 exon, c.1091C > T, p.Pro364Leu.In front of the persistently high level of unconjugated bilirubin, phototherapy was performed without persistent results. A treatment with phenobarbital was then begun and bilirubin level progressively decreased, with a complete and persistent normalization. The therapy was stopped.ConclusionUGT1A1 enzyme activity associated with the P364L mutation has been described as 35.6% of the wild-type enzyme activity. Photo-therapy and phenobarbital can be useful in front of persistently high level of unconjugated bilirubin.Our cases presented high bilirubin values, overlapping between Gilbert syndrome (GS) and Crigler-Najjar syndrome type II (CNS), but the complete normalization of bilirubin makes GS more likely. Homozygous P364L variant can be associated with severe neonatal unconjugated hyperbilirubinemia in Chinese infants, but jaundice can completely resolve in a few months, contrary to what happens in Crigler-Najjar syndrome type II.

A Case of Gilbert Syndrome and Uncontrolled Diabetes Mellitus with Elevated HbA1C Improved with Individualized Homeopathic Medicine

Diabetes mellitus is one of the most common metabolic disorders in the present era from altered lifestyle. Glycosylated hemoglobin (HbA1C) is the most reliable blood parameter for diagnosis and prognosis of diabetes mellitus. Gilbert syndrome in diabetic patients lowers the prevalence of microvascular complications of diabetes mellitus. Even though Gilbert syndrome is a fortunate factor in this patient, progressive weight loss is the raising concern. From proteolysis and diuresis, kidneys can get damaged in course of time. Uncontrolled HbA1C again can increase the risk of complications of diabetes mellitus. In this case, HbA1C and weight loss with diabetes mellitus improved with an individualized homeopathic approach. Natrum Muriaticum was selected on a constitutional basis, and it was administered on an LM scale which helped the patient in bringing down blood parameters and managing weight loss of Diabetes.

Difficulties in diagnosing paroxysmal nocturnal hemoglobinuria in a municipal internal disease hospital

Background: The purpose of this work is to present a case of paroxysmal nocturnal hemoglobinuria in the clinical practice of an internist for the purpose of differential diagnosis with other diseases with the jaundice syndrome in a city hospital.&#x0D; Clinical case description: Patient H., 51-year-old, was seen at the emergency department of the city hospital due to the periodic appearance of jaundice with dark-colored urine and fever. The physical and laboratory examination methods revealed an enlargement of the spleen, signs of mild hemolytic anemia, severe thrombocytopenia, a significant increase in the markers of cytolysis and cholestasis. Proteinuria and cylindruria were noted in the urine analysis. In terms of a differential diagnosis, Gilberts syndrome, viral hepatitis, hemorrhagic fever were considered.&#x0D; Conclusion: Based on the data obtained, hemolytic and uremic syndromes were suspected. A therapy with iron preparations, vitamin B12, infusions of glucose and saline was applied with the positive clinical and laboratory dynamics. GPI-linked glycoproteins were determined on the surface of red blood cells (CD59), neutrophils (CD 24/FLAER), and monocytes by FLAER-/CD14 flow cytometry, which confirmed the diagnosis of paroxysmal nocturnal hemoglobinuria.

Clinical image report of acute Cholangitis in Beta-thalassemia major.

Beta‐thalassemia is congenital red blood cell disorder. Gallstones is a recognized complication due to recurrent hemolysis. Acute cholangitis is a rare complication might occur in patient with beta‐thalassemia. We report a case of acute cholangitis in patient with beta‐thalassemia with Gilbert syndrome. We present a case of a young female of Arabic descent with acute abdomen. Workup revealed acute cholangitis with gallstones in the common bile duct. The ERCP was used to extract the stones than cholecystectomy.

Доброкачественная гипербилирубинемия типа Жильбера

INTRODUCTION: Benign hyperbilirubinemia of Gilbert type affects 10% of population, most commonly men of 20–30 years of age. In the article, description of a classic clinical case illustrating the course of Gilbert syndrome, is given. After an intercurrent infection, a 32-year old man presented with jaundice with elevation of the level of unconjugated bilirubin against the normal background level of enzymes. Bearing in mind a probability of being excluded from the flight crew, the patient agreed to the puncture biopsy of the liver, and the morphological examination of the hepatic tissue confirmed the diagnosis of benign hyperbilirubinemia of Gilbert type. A molecular genetic examination also showed the existence of tyrosine-arginine repeats in the promotor region of uridine diphosphate–glucuronosyltransferase gene. Adequately selected treatment with phenobarbital stimulating the activity of the enzyme, led to normalization of bilirubin level and to improvement of the patient’s well-being. CONCLUSION: Chronic familial non-hemolytic hyperbilirubinemias are often given insufficient attention not only due to the fact that their outcomes do not pose a serious threat to the patient’s health, and, according to the erroneous opinion, are rare, but to a larger extent due to the fact that the diagnosis presents certain difficulties for a therapist or a general practitioner.

Levitt’s CO breath test in the differential diagnosis of chronic isolated hyperbilirubinemia

A key component of the differential diagnosis of isolated hyperbilirubinemia (HB) is distinguishing between hemolytic and non-hemolytic types. Routine hemolysis screening markers have unsatisfactory sensitivity and specificity. Erythrocyte (RBC) lifespan shortening, the gold standard marker of hemolysis, is seldomly measured due to the cumbersome and protracted nature of standard methods. A new Levitt’s CO breath test method may enable simple, rapid RBC lifespan measurement. In this pilot prospective diagnostic study, Levitt’s CO breath test was evaluated to discriminate hemolytic from non-hemolytic HB in adults. One hundred and thirty eligible non-smoking adult patients who were aged 18 or older, referred for chronic (>6 months) isolated HB or had a known diagnosis of isolated HB of a rare cause, were recruited, including 77 with non-hemolytic HB and 53 with hemolytic HB. ROC curve analysis was applied to determine the optimal cutoff for discriminating between hemolytic and non-hemolytic HB, and the performance was calculated. Results showed that the mean RBC lifespan in non-hemolytic HB (93 ± 26 d) was reduced (p = 0.001 vs. normal reference value of 126 d), but longer than that in hemolytic HB (36 ± 17 d; p = 0.001). RBC lifespans did not differ significantly between 26 patients with simple hemolytic HB (32 ± 14 d) and 27 patients with a Gilbert syndrome comorbidity (40 ± 18 d). ROC curve analysis revealed an optimal lifespan cutoff for discriminating between hemolytic and non-hemolytic HB of 60 d (AUC = 0.982), with a diagnostic accuracy of 95.4%, 94.3% sensitivity and 96.1% specificity respectively. These results indicate that Levitt’s CO breath test seems to be very sensitive and specific for detecting hemolysis in adult patients with chronic isolated HB, and could enable simple, rapid, and reliable differential diagnosis of isolated HB. A large-scale validation study of the method is warranted.

Sexual dimorphism: increased sterol excretion leads to hypocholesterolaemia in female hyperbilirubinaemic Gunn rats.

Circulating bilirubin is associated with reduced serum cholesterol concentrations in humans and in hyperbilirubinaemic Gunn rats. However, mechanisms contributing to hypocholesterolaemia remain unknown. Therefore, this study aimed to investigate cholesterol synthesis, transport and excretion in mutant Gunn rats. Adult Gunn and control rats were assessed for daily faecal sterol excretion using metabolic cages, and water was supplemented with [1‐13C]‐acetate to determine cholesterol synthesis. Bile was collected to measure biliary lipid secretion. Serum and liver were collected for biochemical analysis and for gene/protein expression using RT‐qPCR and western blot, respectively. Additionally, serum was collected and analysed from juvenile rats. A significant interaction of sex, age and phenotype on circulating lipids was found with adult female Gunn rats reporting significantly lower cholesterol and phospholipids. Female Gunn rats also demonstrated elevated cholesterol synthesis, greater biliary lipid secretion and increased total faecal cholesterol and bile acid excretion. Furthermore, they possessed increased hepatic low‐density lipoprotein (LDL) receptor and SREBP2 expression. In contrast, there were no changes to sterol metabolism in adult male Gunn rats. This is the first study to demonstrate elevated faecal sterol excretion in female hyperbilirubinaemic Gunn rats. Increased sterol excretion creates a negative intestinal sterol balance that is compensated for by increased cholesterol synthesis and LDL receptor expression. Therefore, reduced circulating cholesterol is potentially caused by increased hepatic uptake via the LDL receptor. Future studies are required to further evaluate the sexual dimorphism of this response and whether similar findings occur in females with benign unconjugated hyperbilirubinaemia (Gilbert's syndrome).Key points Female adult hyperbilirubinaemic (Gunn) rats demonstrated lower circulating cholesterol, corroborating human studies that report a negative association between bilirubin and cholesterol concentrations.Furthermore, female Gunn rats had elevated sterol excretion creating a negative intestinal sterol balance that was compensated for by elevated cholesterol synthesis and increased hepatic low‐density lipoprotein (LDL) receptor expression.Therefore, elevated LDL receptor expression potentially leads to reduced circulating cholesterol levels in female Gunn rats providing an explanation for the hypocholesterolaemia observed in humans with elevated bilirubin levels.This study also reports a novel interaction of sex with the hyperbilirubinaemic phenotype on sterol metabolism because changes were only reported in females and not in male Gunn rats.Future studies are required to further evaluate the sexual dimorphism of this response and whether similar findings occur in females with benign unconjugated hyperbilirubinaemia (Gilbert's syndrome).

Study single nucleotide polymorphism in Promoter region of UGT1A1 Gene in Iraqi Patients with Gilbert's syndrome

This study aimed to detect genetic variants of the UGT1A1 gene in patients with Gilbert's syndrome. To detect this, primers were designed; PCR and direct sequencing were done for the promoter area of the gene as a diagnostic tool for the detection of any polymorphism. Variation and polymorphism were detected within the promoter mutants of the UDP glycosyltransferase _UGT1A1 gene that causes hyperbilirubinemia in a group of Iraqi patients compared with a group of the normal healthy individual as controls. The patients with hyperbilirubinemia in this study were 30 in which the total bilirubin level was more than 12 mg/dl serum; they included 25 males and 5 females, while the control group consisted of 20 healthy individuals. This study was carried out from September 2019 till April 2021. The result displayed high occurrence of Gilbert syndrome within male patients than in females, and regarding the analyses of mutation of bilirubin UDP glycosyltransferase _UGT1A1 gene, it is clear that the genotypic distribution of variation among the hyperbilirubinemia patients included all 30 patients, while SNP was detected in 18 patients out of 30 which indicate that the UGT1A1 gene mutation was a likely risk factor for the development of hyperbilirubinemia related Gilbert syndrome in Iraq. The homozygous and heterozygous polymorphisms A/G inside the promoter region of the UGT1A1 gene were effectively identified by sequencing. Our finding suggests that TA repeats and allele of UGT1A1 polymorphism A/G are associated with Gilbert's syndrome and act as genetic markers of this disease in Iraqi patients. To analyze data and sequence variation in gene, generous software was used after amplifying the gene. All processes include DNA extraction, PCR amplification, sequencing, and assembly.

UGT1A1 gene polymorphisms in patients with Gilbert syndrome and Crigler-Najjar syndrome type Ⅱ

UGT1A1 gene polymorphisms in patients with Gilbert syndrome and Crigler-Najjar syndrome type Ⅱ

Food Faddism Complicating Jaundice in Gilbert’s Syndrome PatientsA Prospective Cohort Study

Introduction: Food faddism is a term that refers to a particular food or food group that is overemphasised in the regular diet or omitted to cure a specific condition. It affects an individual's health by complicating the health status of already infected individuals, which harms their nutritional status in particular, causing macro and micronutrient deficiencies. In the present study, authors have analysed the effect of food faddism in Gilbert’s syndrome patients. The state of vitamin B12 deficiency (Megaloblastic anaemia) is observed because of dietary restrictions due to food myths causing ineffective erythropoiesis prolonging hyperbilirubinemia in Gilbert's syndrome patients. Aim: To study the effect of food faddism on haematological parameters in recently diagnosed Gilbert’s syndrome patients. Materials and Methods: A prospective cohort study was conducted in a tertiary care centre of north coastal Andhra Pradesh, India, from June 2019 to June 2021. A total of 125 consecutive patients, who are newly-diagnosed with Gilbert’s syndrome, were enrolled. A constant rise in the indirect bilirubin levels between 2-5 mg/dL with normal serum liver transaminases was considered for diagnosing Gilbert’s syndrome. On monthly follow-up for six months, 21 patients presented with extreme fatigue and limb paresthesia. Every month during the follow-up, thorough history about any recent changes in food habits was noted. Blood investigations like complete blood pictures and Vitamin B12 levels were done at the time of diagnosis, after six-month follow-up, and after treatment with co-methyl (Cyanocobalamin) B12 injections. Comparison of study variables at the time of diagnosis of Gilbert's syndrome, before and after the treatment with co-methyl (Cyanocobalamin) B12 injections was done using paired t-test based on nature of distribution, and p-value was calculated. Results: Out of 125 Gilbert’s syndrome patients with a mean age distribution of 36.15±11.82 in (109) males and 36.06±11.93 in (16) females, 21 patients presented with symptoms after six months of follow-up, a habit of practicing a fad diet was noted, along with depression of cell lines showing pancytopenia. There was a significant decrease in the mean values of Haemoglobin (Hb) % (12.68 to 7.95), Total Count (TC) (8219.05 to 3819 cells/ cu.mm), Mean Corpuscular Haemoglobin Concentration (MCHC) (33.30 to 32.17) and Vitamin B12 (391.63 to 125.68) and increase in mean value of Mean Corpuscular Volume (MCV) (91.33 to 101.18), at the time of diagnosis and after six months of follow-up. On treatment of the patients with co-methyl (Cyanocobalamin) B12 injections a significant improvement in the mean values of Hb % (7.95 to 13.28), TC (3819 to 8652 cells/cu.mm), MCHC (32.17 to 33.43) and Vitamin B 12 (125.68 to 311.81) along with decrease in the mean value of MCV (101.18 to 90.0) was noted. Conclusion: The most common fad diet followed by Gilbert’s syndrome patients is the restriction of high protein diet (mainly non vegetarian) and bland diet consumption leading to Vitamin B12 deficiency and worsening jaundice. By taking thorough dietary history, considering cultural practices, one can tailor the therapy accordingly. A simple measure like dietary education and busting the myths can improve quality of life by accelerating recovery

A systemic review of association between UDP glucuronosyltransferase family 1 member A1 (UGT1A1) polymorphisms in Gilbert's syndrome in Sickle Cell Disease

Gilbert's syndrome (GS) is a benign hereditary disorder of bilirubin metabolism due to a mutation in the UDP glucuronosyltransferase family 1 member A1 (UGT1A1) gene which results in hyperbilirubinaemia and related complications mainly cholelithiasis. It can be co-inherited along with sickle cell anaemia, thalassaemias and other haemoglobinopathies including glucose-6-phosphate dehydrogenase deficiency, hereditary spherocytosis and cystic fibrosis. More than 100 mutations have been reported in UGT1A1 gene and the most common as insertion of extra (TA) nucleotides in the promoter region of TATA box. The more the number of TA repeats, the higher is the bilirubin levels. These mutations result in a 10%–35% reduction in the UGT1A1 enzyme activity resulting in mild to moderate unconjugated hyperbilirubinaemia and related complications. For diagnosis the mode of inheritance is more important than testing in the patients. However; the inheritance pattern of GS differs in ethnicities. For early diagnosis to prevent worsening of the symptoms and for timely management one should be aware of the inheritance pattern in patient. In this systemic analysis we studied the association between complications in GS with the genotypes and complications. It was found that TA7/7 is more significant in GS with sickle cell disease (SCD) group when compared to healthy controls with 2.2% chances of having this genotype in GS with SCD than healthy controls. The significance of having TA7/7 genotype is similar in GS with SCD and α-thalasaemia group. However, there is a high recommendation to carry out multicentre studies and conduct meta-analyses for establishing universal recommendations.

Can Gilbert's syndrome mitigate chronic lymphocytic leukemia?

The study links two intriguing observations about chronic lymphocytic leukemia and Gilbert's syndrome – the oxidative stress affecting the former, and the anti-oxidative effects of the latter. Our pilot study showed that compared to the general CLL population, the GS/CLL cohort less commonly required therapy and demonstrated a reduced CLL-related mortality. Our findings prompt a speculation that elevated bilirubin in GS could hypothetically attenuate the oxidative stress thereby exerting a safeguarding effect on leukemia pathogenesis. We believe that this hypothesis-generating study could open new avenues for exploring oxidative stress as a potential pathogenetic and, hypothetically, therapeutic target for mitigating CLL

Ayurvedic management of herpes zoster in Rakta-pradoshajaroga (Gilbert's syndrome)

Herpes zoster is an acute viral infection of sensory ganglia and the corresponding cutaneous areas of innervations characterized by fever and localized pain with vesicular skin eruption over single dermatomes. The available conventional treatments such as the use of antiviral drugs, corticosteroids, and topical agents have certain limitations. The condition, if not treated in early stages, becomes a great challenge to the clinician due to a higher rate of complications such as the neurological sequel, palsy, stroke, and cardiovascular events. In Ayurveda, this condition closely resembles Pittajavisarpa. Gilbert's syndrome is an inherited condition in which the liver does not properly process bilirubin, which causes a slight increase in bilirubin level that can be correlated with Kamala (~jaundice) in Ayurveda. Visarpa and Kamala both diseases are Rakta-pradoshajaroga (~blood vitiated disorders). The principle of treatment is Raktapittanashak-kriya (~remedies which balance the Rakta and Pitta dosha). In this case report, a 20-year-old male patient, with Gilbert syndrome presented with herpes zoster was managed with Ayurvedic internal medications such as Sutashekhara rasa, Arogyavardhini vati, Kaishora guggulu, Avipattikara churna, Paripathadi kwatha, and local application of Shatadhouta ghrita. Improvement had been observed in symptoms and in skin lesions after 14 days, whereas hepatic biochemical parameters were restored to normal after 42 days of treatment. No adverse effect pertaining to the prescribed drug was reported during the study period, inferring that, Ayurvedic medicines offer a good approach to manage Rakta-pradoshajaroga.