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Rotor Syndrome

Synonym: Rotor-Type Hyperbilirubinemia

, MD, PhD, , MD, , PhD, and , PhD.

Author Information and Affiliations

Initial Posting: ; Last Update: February 27, 2025.

Estimated reading time: 16 minutes

Summary

Clinical characteristics.

Rotor syndrome is characterized by mild conjugated and unconjugated hyperbilirubinemia that usually begins shortly after birth or in childhood. Jaundice may be intermittent. Conjunctival icterus may be the only clinical manifestation.

Diagnosis/testing.

The diagnosis of Rotor syndrome is established in a proband with isolated, predominantly conjugated hyperbilirubinemia without cholestatic liver injury and typical findings on cholescintigraphy. Identification of biallelic pathogenic variants in SLCO1B1 and SLCO1B3 on molecular genetic testing can confirm the diagnosis when cholescintigraphy is either not available or not recommended due to risks associated with the procedure.

Management.

Treatment of manifestations: No treatment required.

Agents/circumstances to avoid: Although no adverse drug effects have been documented in persons with Rotor syndrome, the absence of the hepatic proteins SLCO1B1 and SLCO1B3 may have serious consequences for liver uptake – and thus for the toxicity of numerous commonly used drugs and/or their metabolites.

Genetic counseling.

Rotor syndrome is inherited in an autosomal recessive digenic manner that clinically resembles monogenic autosomal recessive inheritance. (Although Rotor syndrome is a digenic disorder, pathogenic variants in SLCO1B1 and SLCO1B3 are unlikely to segregate independently.) If both parents are known to be heterozygous for SLCO1B1 and SLCO1B3 pathogenic variants in cis, each sib of an affected individual has at conception a 25% chance of inheriting biallelic pathogenic variants in both SLCO1B1 and SLCO1B3 and being affected; a 50% chance of being an asymptomatic carrier; and a 25% chance of being unaffected and not a carrier. Carriers (i.e., individuals with one, two, or three pathogenic variants) are asymptomatic and are not at risk of developing Rotor syndrome. Once the Rotor syndrome-causing pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.

Diagnosis

Suggestive Findings

Rotor syndrome should be suspected in individuals with the following clinical, laboratory, and cholescintigraphy findings and family history.

Clinical findings

  • Mild jaundice (may be intermittent)
  • Conjunctival icterus (in some affected individuals)
  • Otherwise normal physical examination

Laboratory findings (See Table 1.)

  • Conjugated hyperbilirubinemia with serum total bilirubin concentration usually between 2 and 5 mg/dL but possibly higher. Conjugated bilirubin usually exceeds 50% of total bilirubin.
  • Presence of bilirubin in the urine
  • Absence of hemolysis*
  • Normal serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) activity*
  • Total urinary porphyrins: elevated coproporphyrin

* Tests for hemolysis and measurements of ALT, AST, ALP, and GGT activity are needed to evaluate for hemolytic anemia and hepatobiliary diseases that are considered in the differential diagnosis of Rotor syndrome.

Cholescintigraphy findings. Radiotracers (99mTc-HIDA/99mTc-N [2,6-dimethylphenyl-carbamoylmethyl] iminodiacetic acid, 99mTc-DISIDA/disofenin, 99mTc-BrIDA/mebrofenin) are taken up slowly by the liver and the liver is scarcely visualized; however, the cardiac blood pool is persistently visualized, with prominent excretion by the kidneys.

Family history is consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis.

Table 1.

Laboratory Findings in Rotor Syndrome

Laboratory FindingRotor SyndromeNormal
Blood Total bilirubin 2-5 mg/dL 10.3-1.0 mg/dL 2
Conjugated:total bilirubin ratio >50%<20%
Liver enzymes NormalNormal
Hemolysis NoneNone
Urine Bilirubin PresentNot detected
Coproporphyrins ↑ 2.5-5x normal 3
1.

Rarely, levels exceeding 20 mg/dL are possible [Strassburg 2010].

2.

For total and direct bilirubin in persons older than age one year. Note: Although normal levels of total and direct bilirubin may be higher in the neonatal period and infancy, Rotor syndrome is not usually diagnosed in this age group.

3.

Coproporphyrinuria is frequently observed in those with parenchymal liver diseases. It is not specific to Rotor syndrome.

Establishing the Diagnosis

Clinical Diagnosis

The clinical diagnosis of Rotor syndrome can be established in a proband with isolated, predominantly conjugated hyperbilirubinemia without cholestasis or liver injury and typical findings on cholescintigraphy.

Molecular Diagnosis

Identification of biallelic pathogenic (or likely pathogenic) variants in SLCO1B1 and SLCO1B3 on molecular genetic testing can confirm the diagnosis when cholescintigraphy is either not available or not recommended due to risks associated with the procedure (see Table 2).

Note: (1) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [Richards et al 2015]. Reference to "pathogenic variants" in this GeneReview is understood to include likely pathogenic variants. (2) Identification of biallelic variants of uncertain significance (or of one known pathogenic variant and one variant of uncertain significance) does not establish or rule out the diagnosis.

Molecular genetic testing approaches can include a combination of concurrent gene testing and multigene panel testing.

  • Concurrent gene testing. Sequence analysis of SLCO1B1 and SLCO1B3 detects missense, nonsense, and splice site variants and small intragenic deletions/insertions. Note: Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If only one or no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications.
  • A multigene panel that includes SLCO1B1, SLCO1B3, and other genes of interest (see Differential Diagnosis) may be considered to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
    For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.

Table 2.

Molecular Genetic Testing Used in Rotor Syndrome

Gene 1, 2Proportion of Rotor Syndrome Attributed to Pathogenic Variants in GeneProportion of Pathogenic Variants 3 Identified by Method
Sequence analysis 4Gene-targeted deletion/duplication analysis 5
SLCO1B1 100% 680% 7, 820% 7
SLCO1B3 60% 7, 840% 7
1.

Genes are listed in alphabetic order.

2.
3.

See Molecular Genetics for information on variants detected in these genes.

4.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; exon or whole-gene deletions/duplications are frequent. For issues to consider in interpretation of sequence analysis results, click here.

5.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, and a gene-targeted microarray designed to detect single-exon deletions or duplications. Exome and genome sequencing may be able to detect deletions/duplications using breakpoint detection or read depth; however, sensitivity can be lower than gene-targeted deletion/duplication analysis.

6.

The Rotor syndrome locus comprises both SLCO1B1 and SLCO1B3, which lie very close together on the same chromosome. All individuals with Rotor syndrome who have undergone molecular testing have had biallelic inactivating pathogenic variants in both SLCO1B1 and SLCO1B3.

7.

A splice site variant, a 7.2-kb deletion removing exon 13, a 6.1-kb LINE-1 (L1) insertion in intron 5, and a complex rearrangement in which insertion of L1 in intron 3 is directly followed by a 1185-bp inversion encompassing exon 4, were found in SLCO1B3. A 405-kb deletion including exons 4-16 of SLCO1B3 and the entire deletion of SLCO1B1 has also been reported. Data are derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020].

8.

Of the seven individuals reported by Kagawa et al [2015] with biallelic SLC01B1 and SLC01B3 pathogenic variants, six individuals of Japanese ancestry were homozygous for an insertion of a ~6.1-kb L1 retrotransposon in intron 5 of SLCO1B3 resulting in aberrant splicing. One individual with a homozygous null variant in SLCO1B1 and a complex rearrangement in SLCO1B3 in which insertion of L1 in intron 3 is directly followed by a 1185-bp inversion encompassing exon 4 was reported by Zhou et al [2020].

Other Testing

Liver biopsy. Liver histology is normal in persons with Rotor syndrome; therefore, suspicion of hereditary jaundice is not an indication for liver biopsy. Immunohistologic staining does not detect hepatic proteins SLCO1B1 and SLCO1B3 at the sinusoidal membrane of hepatocytes. Note: Expression of MRP2, frequently absent in Dubin-Johnson syndrome, is normal [Hrebícek et al 2007], and dark melanin-like pigment in hepatocytes typical of Dubin-Johnson syndrome is not present (see Differential Diagnosis).

Clinical Characteristics

Clinical Description

The only clinical feature of Rotor syndrome is mild jaundice due to conjugated and unconjugated hyperbilirubinemia that usually begins shortly after birth or in childhood.

Jaundice may be intermittent. Conjunctival icterus may be the only clinical manifestation.

Genotype-Phenotype Correlations

Hyperbilirubinemia develops only in persons with biallelic inactivating pathogenic variants in both SLCO1B1 and SLCO1B3 [van de Steeg et al 2012]. Presence of at least one wild type (functional) allele of either SLCO1B1 or SLCO1B3 prevents Rotor-type hyperbilirubinemia.

A combination of a variant that results in reduced activity in one allele of either SLCO1B1 or SLCO1B3 with deleterious variants affecting the remaining three alleles has not been documented.

Prevalence

The prevalence of Rotor syndrome is unknown but is very low (<1:1,000,000).

A high carrier frequency of an insertion of a ~6.1-kb L1 retrotransposon in intron 5 of SLCO1B3 resulting in aberrant splicing was discovered in East Asian populations (10.1%), especially in Southern Han Chinese (18.5%) [Kagawa et al 2015, Kim et al 2022], but this pathogenic variant was almost absent in other studied populations.

Differential Diagnosis

Inherited disorders of bilirubin clearance can present with either conjugated or unconjugated hyperbilirubinemia. Dubin-Johnson syndrome, a benign conjugated hyperbilirubinemia similar to Rotor syndrome, is caused by decreased secretion of conjugated bilirubin into bile. Defects in bilirubin conjugation resulting in increased levels of unconjugated bilirubin are represented by Gilbert syndrome, Crigler-Najjar syndrome type II, and Crigler-Najjar syndrome type I (a rare, severe, life-threatening disease associated with kernicterus typically manifesting within the first days after birth). Since Rotor syndrome is usually diagnosed after the neonatal period, only benign forms of genetic jaundice are included in the differential diagnosis (see Table 3).

Table 3.

Benign Forms of Genetic Jaundice in the Differential Diagnosis of Rotor Syndrome

Gene(s)DisorderClinical & Laboratory FindingsComment
UGT1A1 Gilbert syndrome 1 (OMIM 143500)
  • Benign
  • Hyperbilirubinemia (<6 mg/dL) is predominantly unconjugated, w/conjugated bilirubin <20% of total serum bilirubin.
  • Most frequently occurring form of hereditary jaundice, affecting ~5%-10% of all Europeans
Gilbert syndrome & Crigler-Najjar syndrome type II have quantitatively different consequences on UGT1A1 enzyme activity. Since plasma bilirubin level is not stable, the phenotypes may overlap in the same person. However, unconjugated hyperbilirubinemia assoc w/homozygous A(TA)7TAA genotype and no pathogenic variants in the UGT1A1 coding region should always be diagnosed as Gilbert syndrome.
Crigler-Najjar syndrome, type II 2 (Arias syndrome) (OMIM 606785)
  • Benign
  • Hyperbilirubinemia is predominantly unconjugated (range: 6-20 mg/dL).
ABCC2 Dubin-Johnson syndrome 3 (DJS) (OMIM 237500)
  • More common than Rotor syndrome
  • In addition to jaundice, abdominal pain & hepatomegaly may be present in some persons w/DJS, although DJS is typically benign.
See Table 4 for comparison of laboratory findings in DJS & Rotor syndrome.
1.

Caused by pathogenic variants in UGT1A1 that decrease the rate of bilirubin conjugation catalyzed by UDP-glucuronosyltransferase 1A1 (UGT1A1). Associated pathogenic variants include the promoter TATA repeat variation A(TA)7TAA (normal: A(TA)6TAA), which is often combined with the promoter SNP c.[-3279T>G], or missense variants in the coding region of UGT1A1, which are frequent in the Japanese population but rare in Europeans.

2.

Caused by pathogenic variants in the coding region of UGT1A1.

3.

Disorder of secretion of conjugated bilirubin into bile.

Table 4.

Comparison of Findings in Dubin-Johnson Syndrome and Rotor Syndrome

FindingRotor SyndromeDubin-Johnson SyndromeNormal
Blood Total bilirubin 2-5 mg/dL 12-5 mg/dL 10.3-1.0 mg/dL 2
Conjugated:total bilirubin ratio >50%>50%<20%
Liver enzymes 3 NormalNormalNormal
Hemolysis 4 NoneNoneNone
Urine Bilirubin Present; urine may be dark.Present; urine may be dark.Not detected
Porphyrins Total porphyrin output ↑; coproporphyrin ↑ 2.5-5x normalTotal porphyrin output normal 5<200 μg in 24 hrs 6
Disappearance of plasma anionic compounds 7 Severely delayedDelayedRapid
Cholescintigraphy Scarcely visualized on cholescintigraphy, w/slow liver uptake, persistent visualization of cardiac blood pool, & prominent kidney excretionVisualization of liver is normal or somewhat delayed but filling of gallbladder is absent or delayed.Normal
1.

Rarely, levels exceeding 20 mg/dL are possible [Strassburg 2010].

2.

For total and direct bilirubin in persons older than age one year. Note: Although normal levels of total and direct bilirubin may be higher in the neonatal period and infancy, Rotor syndrome is not usually diagnosed in this age group.

3.

Serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) activity

4.

Red blood count and reticulocyte count

5.

Total urinary porphyrin output is normal; however, predominance of coproporphyrin isomer I among urinary porphyrin species is observed on chromatography.

6.

Total urinary porphyrin output

7.

Includes bromosulfophthalein (BSP), indocyanine green, and cholescintigraphy radiotracers (99mTc-HIDA/99mTc-N [2,6-dimethylphenyl-carbamoylmethyl] iminodiacetic acid, 99mTc-DISIDA/disofenin, 99mTc-BrIDA/mebrofenin). Note: In Dubin-Johnson syndrome, BSP conjugates reappear in the blood after administration of unconjugated BSP; this is not the case in Rotor syndrome.

Cholestatic liver diseases and/or bile duct obstruction should be suspected whenever hyperbilirubinemia is accompanied by clinical signs other than jaundice and by elevation of serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT) activity. The same holds true for any abnormal findings in the gallbladder and the biliary tree obtained by imaging and/or endoscopy techniques. (See also Pediatric Genetic Cholestatic Liver Disease Overview.)

Hemolytic jaundice is characterized by predominantly unconjugated hyperbilirubinemia and signs of increased hemolysis.

Management

No clinical practice guidelines for Rotor syndrome have been published as no treatment or surveillance is recommended.

Evaluations Following Initial Diagnosis

In most instances an individual diagnosed with Rotor syndrome is the child of a consanguineous couple. In some centers, identification of consanguinity may be an indication for consultation with a clinical geneticist, certified genetic counselor, certified genetic nurse, or genetics advanced practice provider (nurse practitioner or physician assistant).

Treatment of Manifestations

No treatment is required.

Agents/Circumstances to Avoid

No adverse drug effects have been documented in Rotor syndrome; however, the absence of the hepatic proteins SLCO1B1 and SLCO1B3 may have serious consequences for liver uptake and toxicity of numerous commonly used drugs and/or their metabolites, which enter the liver via either of the two OATP1B transporters.

A list of drugs that enter the liver mainly via SLCO1B1 and whose pharmacokinetics are known to be influenced by genetic variability in SLCO1B1 or inhibition of SLCO1B1/3 has been published [Niemi et al 2011, Garrison et al 2020, Anabtawi et al 2022]. Some of these drugs are also taken up by SLCO1B3 [Shitara 2011].

  • Statins – simvastatin, atorvastatin, pravastatin, pitavastatin, rosuvastatin
  • Ezetimibe
  • Anticancer drugs – methotrexate and irinotecan, cabazitaxel, some tyrosine kinase inhibitors (e.g., sunitinib)
  • Sartans – olmesartan and valsartan
  • Rifampicin
  • Mycophenolic acid
  • Torsemide
  • Thiazolidine diones – pioglitazone and rosiglitazone
  • Glinides – nateglinide and repaglinide
  • Lopinavir
  • Fexofenadine
  • Cyclosporin A

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

No special pregnancy management issues from the perspective of either an affected mother or an affected fetus are known.

Of note, during pregnancy the hyperbilirubinemia of Rotor syndrome may complicate the diagnosis and management of liver disease related to pregnancy (e.g., intrahepatic cholestasis of pregnancy) and liver disease not related to pregnancy.

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members; it is not meant to address all personal, cultural, or ethical issues that may arise or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Rotor syndrome is inherited in an autosomal recessive digenic manner. It is caused by biallelic pathogenic variants in both SLCO1B1 and SLCO1B3 that result in complete functional deficiencies of both protein products (SLCO1B1 and SLCO1B3, respectively) [van de Steeg et al 2012].

Note: Although Rotor syndrome is a digenic disorder, pathogenic variants in SLCO1B1 and SLCO1B3 are unlikely to segregate independently and, consequently, the pattern of inheritance of Rotor syndrome is similar to that of monogenic autosomal recessive disorders.

Risk to Family Members

Parents of a proband

  • The parents of an affected child are presumed to be heterozygous for pathogenic variants in both SLCO1B1 and SLCO1B3 (i.e., SLCO1B1 and SLCO1B3 pathogenic variants in cis).
  • If a molecular diagnosis has been established in the proband, molecular genetic testing of the parents of the proband can confirm their genetic status and allow reliable recurrence risk assessment.
  • Individuals with heterozygous SLCO1B1 and SLCO1B3 pathogenic variants in cis (carriers) are asymptomatic and are not at risk of developing Rotor syndrome. Hyperbilirubinemia develops only in persons with biallelic inactivating pathogenic variants in both SLCO1B1 and SLCO1B3 [van de Steeg et al 2012]; the presence of at least one wild type (functional) allele of either SLCO1B1 or SLCO1B3 prevents Rotor-type hyperbilirubinemia.

Sibs of a proband

  • If both parents are known to be heterozygous for SLCO1B1 and SLCO1B3 pathogenic variants in cis, each sib of an affected individual has at conception a 25% chance of inheriting biallelic pathogenic variants in both SLCO1B1 and SLCO1B3 and being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
  • Carriers (i.e., individuals with one, two, or three pathogenic variants) are asymptomatic and are not at risk of developing Rotor syndrome.

Offspring of a proband. Unless an affected individual's reproductive partner also has Rotor syndrome or is a carrier, offspring will be obligate heterozygotes (carriers) for pathogenic variants in SLCO1B1 and SLCO1B3.

Other family members. Each sib of the proband's parents is at 50% risk of being a carrier for SLCO1B1 and SLCO1B3 pathogenic variants.

Carrier Detection

Carrier testing for at-risk relatives requires prior identification of the SLCO1B1 and SLCO1B3 pathogenic variants in the family.

Related Genetic Counseling Issues

Because most individuals with Rotor syndrome are born to consanguineous couples, the diagnosis of Rotor syndrome may coincidentally identify such consanguinity. In some centers, this may be an indication for clinical genetics consultation and/or genetic counseling.

Family planning

  • The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.

Prenatal Testing and Preimplantation Genetic Testing

Once the Rotor syndrome-causing pathogenic variants have been identified in an affected family member, prenatal and preimplantation genetic testing are possible.

Requests for prenatal testing for benign, clinically unimportant conditions such as Rotor syndrome are not expected to be common. Differences in perspective may exist among medical professionals and within families regarding the use of prenatal and preimplantation genetic testing. While most health care professionals would consider use of prenatal and preimplantation genetic testing to be a personal decision, discussion of these issues may be helpful.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

Rotor Syndrome: Genes and Databases

GeneChromosome LocusProteinHGMDClinVar
SLCO1B1 12p12​.1 Solute carrier organic anion transporter family member 1B1 SLCO1B1 SLCO1B1
SLCO1B3 12p12​.2 Solute carrier organic anion transporter family member 1B3 SLCO1B3 SLCO1B3

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for Rotor Syndrome (View All in OMIM)

237450HYPERBILIRUBINEMIA, ROTOR TYPE; HBLRR
604843SOLUTE CARRIER ORGANIC ANION TRANSPORTER FAMILY, MEMBER 1B1; SLCO1B1
605495SOLUTE CARRIER ORGANIC ANION TRANSPORTER FAMILY, MEMBER 1B3; SLCO1B3

Molecular Pathogenesis

In individuals with Rotor syndrome, liver histologic findings are normal; however, expression of SLCO1B1 (solute carrier organic anion transporter family member 1B1, encoded by SLCO1B1; also known as OATP1B1) and SLCO1B3 (solute carrier organic anion transporter family member 1B3, encoded by SLCO1B3; also known as OATP1B3) is completely absent. The functional consequence of this is that liver uptake of bilirubin mono- and diglucuronides is hampered, causing increased plasma bilirubin-glucuronide levels and jaundice.

Deficiency of SLCO1B1 and SLCO1B3 also explains the poor uptake by the liver of unconjugated bilirubin and anionic dyes such as bromosulfophthalein, indocyanine green, and cholescintigraphy radiotracers (99mTc-HIDA and related compounds). It also underlies earlier observations that in individuals with Rotor syndrome conjugated bromosulfophthalein does not appear in the blood after intravenous administration of its unconjugated precursor. Impaired uptake and biliary secretion of indocyanine green has been attributed to isolated SLCO1B3 deficiency [Kagawa et al 2017]. Whether simultaneous presence of SLCO1B1 and SLCO1B3 deficiency is essential for impaired uptake of bromosulfophthalein and cholephilic radiotracers remains to be established.

Reduced hepatic (re)uptake of coproporphyrin isomers probably underlies the increased urinary excretion of coproporphyrins.

Mechanism of disease causation. Loss of function

Table 5.

Gene-Specific Laboratory Considerations

GeneSpecial Consideration
SLCO1B3 Failure to amplify exon 5 may indicate the intronic L1 insertion reported by Kagawa et al [2015]. Neither the L1 insertion [Kagawa et al 2015] nor the complex rearrangement [Zhou et al 2020] is detectable by routine sequence analysis, but both can be detected by sequencing of fragments amplified by specifically designed PCR.

Chapter Notes

Author Notes

Milan Jirsa (zc.meki@ijim) is actively involved in clinical research regarding individuals with Rotor syndrome. Dr Jirsa would be happy to communicate with persons who have any questions regarding diagnosis of Rotor syndrome or other considerations.

Dr Jirsa is also interested in hearing from clinicians treating families affected by Rotor syndrome in whom no causative variant has been identified through molecular genetic testing of the genes known to be involved in this group of disorders.

Contact Dr Jirsa to inquire about review of SLCO1B1 or SCLO1B3 variants of uncertain significance.

Acknowledgments

Milan Jirsa has been supported by DRO IKEM IN 00023001.

Revision History

  • 27 February 2025 (sw) Comprehensive update posted live
  • 11 July 2019 (sw) Comprehensive update posted live
  • 13 December 2012 (bp) Review posted live
  • 6 September 2012 (mj) Original submission

References

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