Sodium taurocholate cotransporting polypeptide (NTCP) deficiency: Identification of a novel <i>SLC10A1</i> mutation in two unrelated infants presenting with neonatal indirect hyperbilirubinemia and remarkable hypercholanemia

Qiu, Jian-Wu; Deng, Mei; Cheng, Ying; Atif, Raza-Muhammad; Lin, Wei‐Xia; Guo, Li; Li, Hua; Song, Yuan‐Zong

doi:10.18632/oncotarget.22503

Cited by 26 publications

(34 citation statements)

References 38 publications

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“…The bile salt cycle is called enterohepatic circulation [17]. Due to the impaired function of sodium-dependent bile acid in hepatocytes of patients with NTCPD; thus, these patients could have plasma bile acid is increased and jaundice [10,14]. In this case, the patient appeared jaundiced after birth.…”

Section: Discussionmentioning

confidence: 99%

“…We provide information about NTCPD to alleviate their anxiety. The primary manifestations of NTCPD are persistently high TBA [10], neonatal jaundice [12], and fat-soluble vitamin deficiency [4]. In addition, some female patients will have increased TBA during pregnancy [7].…”

Section: Psychological Carementioning

confidence: 99%

“…In 2015, Vaz [4] et al reported the first NTCP deficiency (NTCPD) in a patient who presented extremely elevated total bile acids (TBA) in plasma, mild hypotonia, growth retardation, and delayed motor milestones. Subsequently, several patients with NTCPD have been reported, with the primary manifestation of persistently elevated TBA [3,[5][6][7][8][9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

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Nursing Care of an Extremely Preterm Infant with Sodium Taurocholate Cotransporting Polypeptide Deficiency: A Case Report

Ni¹,

Song²,

Chen³

et al. 2020

AJNS

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Sodium taurocholate cotransporting polypeptide (NTCP) is a protein encoded by the solute carrier family 10 member 1 gene and expressed in the basolateral membrane of the hepatocyte to uptake conjugated bile acids from the plasma. This study reported an extremely premature infant (EPI) with NTCP deficiency (NTCPD). The patient presented with jaundice, persistently elevated total bile acids, 25-(OH)-VitD deficiency, and cleft palate. Nursing care mainly focused on disease surveillance, jaundice care, nutrition, kangaroo mother care, and psychological care. In response to 5 months of the nursing care, the infant's weight reached 3.324 kg, the jaundice was alleviated, and the infant gained the ability to suck milk. However, his TBA levels were abnormally elevated, and 25-(OH)-VitD was still deficient when the patient was discharged from hospital. The nurses taught the patient's parents the importance of monitoring liver function and trace elements during a routine outpatient visit. Telephone follow-up 1 year later showed that the patient was in good health with no obvious clinical manifestations. This article reports our experiences in caring for an EPI with NTCPD. To the best of our knowledge, this is the first case report worldwide in NTCPD nursing care.

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Section: Discussionmentioning

confidence: 99%

Section: Psychological Carementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nursing Care of an Extremely Preterm Infant with Sodium Taurocholate Cotransporting Polypeptide Deficiency: A Case Report

Ni¹,

Song²,

Chen³

et al. 2020

AJNS

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“…Therefore, we decided to select two carriers from the SLC10 carrier family, which are more unique in the sense of substrate specificity and tissue expression and which both show sodium-dependent transport of sulfated steroids (15,26). In both carriers, genetic variants or mutations were described before with significantly reduced transport activity, associated with increased plasma levels of their substrates (27)(28)(29)(30). However, as the determination of DHEAS serum levels is not included in standard diagnostics, elevated DHEAS levels may have been overseen in patients with such carrier defects.…”

Section: Case Presentationmentioning

confidence: 99%

Very High Dehydroepiandrosterone Sulfate (DHEAS) in Serum of an Overweight Female Adolescent Without a Tumor

et al. 2020

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Introduction: An increase of serum dehydroepiandrosterone (DHEA) sulfate (DHEAS) is observed in premature adrenarche and congenital adrenal hyperplasia. Very high DHEAS levels are typical for adrenal tumors. Approximately 74% of DHEAS is hydrolyzed to DHEA by the steroid sulfatase (STS). The reverse reaction is DHEA sulfation. Besides these two enzyme reactions, the DHEAS transported through the cell membrane is important for its distribution and excretion. Case Presentation: We present a female adolescent with overweight and a very high DHEAS. The presence of a DHEAS-producing tumor was rejected using ultrasonography, Magnetic Resonance Tomography (MRT), and dexamethasone suppression. STS deficiency was suspected. Sequence analysis revealed a heterozygous nonsense mutation which predicts a truncation of the carboxyl region of the STS that is implicated in substrate binding. No partial gene deletion outside exon 5 was detected by multiplex ligation-dependent probe amplification. The bioassay revealed normal enzyme activity in the patient's leukocytes. A defect of transporter proteins was suggested. Both efflux [multidrug-resistance protein (MRP)2 and breast cancer-resistance protein (BCRP)] and uptake [organic anion-transporting polypeptide (OATP) and organic anion transporter (OAT) carriers] transporters were studied. Sequence analysis of exons revealed a heterozygous Q141K variant for BCRP. Conclusions: A novel heterozygous nonsense mutation in the STS gene and a known heterozygous missense variant in the BCRP gene were found. The heterozygous nonsense mutation in the STS gene is not supposed to be responsible for STS deficiency. The BCRP variant is associated with reduced efflux transport activity only in its homozygous state. The combination of the two heterozygous mutations could possibly explain the observed high levels of DHEAS and other sulfated steroids.

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“…Although the gene SLC10A1 was cloned as early as in 1994 (Hagenbuch and Meier 1994) while NTCP function has been studied extensively (Ho et al 2004;Yan et al 2012Yan et al , 2014, the first patient with NTCP deficiency was just reported in 2015 as a homozygote of the SLC10A1 variant c.755G>A(p.Arg252His) (Vaz et al 2015). Thereafter, only a limited number of such patients harboring biallelic pathogenic SLC10A1 variants including c.800C>T(p.Ser267Phe), c.263T>C(p.Ile88Thr) and c.615_618del (p.Ser206Profs*12) have been reported (Deng et al 2016;Liu et al 2017;Qiu et al 2017;Song and Deng 2017;Van Herpe et al 2017;Tan et al 2018), while the clinical features of NTCP deficiency remained far from being well understood. In this paper, five patients with NTCP deficiency were diagnosed via SLC10A1 analysis in two unrelated families.…”

Section: Introductionmentioning

confidence: 99%

Intrahepatic Cholestasis of Pregnancy as a Clinical Manifestation of Sodium-Taurocholate Cotransporting Polypeptide Deficiency

Chen

Deng

Rauf

et al. 2019

Tohoku J. Exp. Med.

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Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-related liver disorder. Although the etiology of ICP is not fully understood thus far, some genetic factors might contribute to the development of this condition. Sodium-taurocholate cotransporting polypeptide (NTCP), the protein encoded by the gene Solute Carrier Family 10, Member 1 (SLC10A1), is the primary transporter expressed in the basolateral membrane of the hepatocyte to uptake conjugated bile salts from the plasma. NTCP deficiency arises from biallelic SLC10A1 mutations which impair the NTCP function and cause intractably elevated levels of total bile acids (TBA) in the plasma (hypercholanemia). In this study, all the SLC10A1 exons and their flanking sequences were analyzed by Sanger sequencing to investigate the etiology for hypercholanemia in two male infants aged 2 and 20 months, respectively, from two unrelated families. As a result, both patients are homozygous for the reported pathogenic variant c.800C>T (p.Ser267Phe) that could impair the NTCP function to uptake bile acids, and the diagnosis of NTCP deficiency was thus made. Their mothers are also homozygotes of the same variant and both had been diagnosed to have ICP in the third trimester, with one of them undergoing cesarean section. The father of the first patient in this paper has the same SLC10A1 genotype c.800C>T/c.800C>T, also exhibiting slight hypercholanemia with a plasma TBA level of 21.5 μmol/L. In conclusion, we suggest that with hypercholanemia being a common laboratory change, NTCP deficiency may be a genetic factor leading to ICP and even cesarean section in clinical practice.

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Sodium taurocholate cotransporting polypeptide (NTCP) deficiency: Identification of a novel SLC10A1 mutation in two unrelated infants presenting with neonatal indirect hyperbilirubinemia and remarkable hypercholanemia

Cited by 26 publications

References 38 publications

Nursing Care of an Extremely Preterm Infant with Sodium Taurocholate Cotransporting Polypeptide Deficiency: A Case Report

Nursing Care of an Extremely Preterm Infant with Sodium Taurocholate Cotransporting Polypeptide Deficiency: A Case Report

Very High Dehydroepiandrosterone Sulfate (DHEAS) in Serum of an Overweight Female Adolescent Without a Tumor

Intrahepatic Cholestasis of Pregnancy as a Clinical Manifestation of Sodium-Taurocholate Cotransporting Polypeptide Deficiency

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