Atypical presentation and delayed diagnosis in a case of primary bile acid synthesis disorder

Garfia Castillo, Cristina; Manzanares López-Manzanares, Javier; García Silva, M. Teresa

doi:10.1016/j.medcle.2016.04.031

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Teresa García Silva" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Cristina" "apellidos" => "Garfia Castillo" "email" => array:1 [ 0 => "cgarfia@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Javier" "apellidos" => "Manzanares López-Manzanares" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "M. Teresa" "apellidos" => "García Silva" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Medicina de Aparato Digestivo, Hospital Universitario 12 de Octubre, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Pediatría, Hospital Universitario 12 de Octubre, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Presentación atípica y diagnóstico tardío en un caso de déficit primario de ácidos biliares" ] ] "textoCompleto" => "Inborn errors of bile acid metabolism are rare genetic diseases. The most common error is the 3beta-hydroxy-delta-5-C27 steroid dehydrogenase (3beta-HSDH) deficiency. It usually occurs in childhood as a progressive cholestasis with severe chronic liver disease, steatorrhea and fat-soluble vitamin deficiency. We report the case of a patient without liver disease but with intense steatorrhea and severe malabsorption of fat-soluble vitamins difficult to control until he was diagnosed with 3beta-HSDH deficiency at the age of 20 and he initiated treatment with bile acids.This is a male monitored for diarrhea since the age of 2 months old. At the age of 3 years, he required hospitalization from severe coagulopathy due to vitamin K deficiency, very pathological steatorrhea (135g fat/day) and fat-soluble vitamin deficiency (A, D, E). Clinicians were unable to establish its etiology. Blood test: GPT 61, total bilirubin 1.8, (BD 1.2), cholesterol 94; the remaining parameters were normal. The antibodies of celiac disease, apolipoproteins A and B, bile acids, d-xylose, fecal chymotrypsin, sweat test, intestinal biopsy and colonoscopy with biopsies were normal. Liver biopsy showed small areas of fibrosis, with no other findings. He received empirical treatment with pancreatic enzymes, ursodeoxycholic acid and vitamins A, D, E and K, with partial improvement of steatorrhea (50g/day), but failing to correct vitamin deficiencies despite replacement with high doses. At the age of 10 he presented xerophthalmia due to vitamin A deficiency, and since the age of 9, walking difficulty, being diagnosed with symptomatology similar to Friedreich's ataxia due to involvement of the spinal posterior roots caused by deficiency of vitamin E. During adolescence, intestinal biopsy, liver biopsy, elastase and fecal chymotrypsin, were repeated, being normal. At the age of 20, the patient underwent bile acid blood test performed by HPLC/Q-TRAP® blood method, detecting highly increased excretion of di and trihydroxy cholanoic acid and glycoconjugates; in urine it allowed to see the presence of abnormal bile acid metabolites (di and trihydroxy cholanoic acids with glycine and sulfate conjugates) in large quantity and very low excretion of primary bile acids. The determination of 7-dehydrocholesterol by quantification with GC/SIM/MS showed highly increased levels (6.98μmol/l; vn 0.74–1.30). This allowed to diagnose the patient with 3beta-HSDH deficiency. The study of HSD3B7 gene mutations showed the patient was homozygous for the switch from glutamic acid to lysine at position 167 in exon 4 (E167K). Treatment was initiated with bile acids, initially with chenodeoxycholic acid, and when available, with cholic acid, normalizing steatorrhea and controlling plasma levels of fat-soluble vitamins.3beta-HSDH deficiency is a rare disease.<a class="elsevierStyleCrossRef" href="#bib0055">1</a> In 1987, Clayton et al.<a class="elsevierStyleCrossRef" href="#bib0060">2</a> reported the first case of 3beta-HSDH deficiency. Although a wide phenotypic variability in 3beta-HSDH deficiency has been observed,<a class="elsevierStyleCrossRefs" href="#bib0055">1,3</a> most often it occurs as a severe neonatal cholestasis very similar to progressive familial intrahepatic cholestasis symptoms but without pruritus and with fat-soluble vitamin deficiencies. Akobeng et al.<a class="elsevierStyleCrossRef" href="#bib0070">4</a> reported 2 cases in which steatorrhea and fat-soluble vitamin deficiency were the initial presentation of the disease. One of them subsequently developed jaundice. Isolated cases with signs of chronic hepatitis have also been reported in the second decade of life.<a class="elsevierStyleCrossRefs" href="#bib0075">5,6</a> However, our patient did not show hepatic involvement.This entity is inherited in an autosomal recessive inheritance pattern.<a class="elsevierStyleCrossRef" href="#bib0070">4</a> It is caused by mutations in the HSD3B7 gene, located on chromosome 16 (16p 11.2).<a class="elsevierStyleCrossRef" href="#bib0085">7</a> In this patient the E167K mutation was detected in homozygosis in exon 4, not reported in other individuals with 3beta-HSDH deficiency.The definitive diagnosis is usually provided after demonstrating abnormal bile acids in urine and plasma through mass spectrometry,<a class="elsevierStyleCrossRef" href="#bib0090">8</a> being a key factor for diagnosis, as in this case. Most patients with 3beta-HSDH deficiency have abnormal urine bile acids, preferably consisting of 3beta-hydroxy group sulfate and glycine conjugates and absence of primary bile acids.<a class="elsevierStyleCrossRef" href="#bib0095">9</a>It is essential to provide a diagnosis because it is a treatable disease. It responds extremely well to bile acid replacement treatment, normalizing liver function and correcting malabsorption of fat-soluble vitamins. This has been achieved with chenodeoxycholic acid alone, with chenodeoxycholic acid and cholic acid, with chenodeoxycholic acid and ursodeoxycholic and with cholic acid alone. The drug of choice is cholic acid because it is not hepatotoxic, and it has been proven safe and effective.<a class="elsevierStyleCrossRef" href="#bib0100">10</a> After initiation of therapy, steatorrhea and fat-soluble vitamin deficiency disappeared in this patient.In cases of steatorrhea of unknown etiology, inborn errors of bile acid metabolism should be considered for providing a diagnosis and early initiation of therapy, preventing from irreparable damage." "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Garfia Castillo C, Manzanares López-Manzanares J, García Silva MT. Presentación atípica y diagnóstico tardío en un caso de déficit primario de ácidos biliares. Med Clin (Barc). 2015;145:e39–e40." ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular genetic and bile acid profiles in two Japanese patients with 3β-hidroxy-▵5-C27-steroid dehydrogenase isomerase deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Mizuochi" 1 => "A. Kimura" 2 => "I. Ueki" 3 => "T. Takahashi" 4 => "T. Hashimoto" 5 => "A. Takao" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1203/PDR.0b013e3181eb0188" "Revista" => array:6 [ "tituloSerie" => "Pediatr Res" "fecha" => "2010" "volumen" => "68" "paginaInicial" => "258" "paginaFinal" => "263" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20531254" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0060" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Familial giant cell hepatitis associated with synthesis of 3 beta, 7 alpha-dihydroxy- and 3 beta, 7 alpha, 12 alpha-trihydroxy-5-cholenoic acids" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.T. Clayton" 1 => "J.V. Leonard" 2 => "A.M. Lawson" 3 => "K.D. Setchell" 4 => "S. Andersson" 5 => "B. Egastad" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI112915" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "1987" "volumen" => "79" "paginaInicial" => "1031" "paginaFinal" => "1038" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3470305" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0065" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Homozygosity mapping identifies a bile acid biosynthetic defect in an adult with cirrhosis of unknown etiology" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "V. Molho-Pessach" 1 => "J.J. Rios" 2 => "C. Xing" 3 => "K.D. Setchell" 4 => "J. Cohen" 5 => "H.H. Hobbs" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.24781" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2012" "volumen" => "55" "paginaInicial" => "1139" "paginaFinal" => "1145" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22095780" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0070" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An inborn error of bile acid synthesis (3β-hydroxy-Δ5-C27-steroid dehydrogenase deficiency) presenting as malabsorption leading to rickets" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A.K. Akobeng" 1 => "P.T. Clayton" 2 => "V. Miller" 3 => "M. Super" 4 => "A.G. Thomas" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Dis Child" "fecha" => "1999" "volumen" => "80" "paginaInicial" => "463" "paginaFinal" => "465" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10208955" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0075" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inborn errors of bile acid metabolism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.E. Heubi" 1 => "K.D. Setchell" 2 => "K.E. Bove" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1055/s-2007-985073" "Revista" => array:6 [ "tituloSerie" => "Semin Liver Dis" "fecha" => "2007" "volumen" => "27" "paginaInicial" => "282" "paginaFinal" => "294" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17682975" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0080" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cholestatic liver disease in adults may be due to an inherited defect in bile acid biosynthesis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Fisher" 1 => "K. Bodin" 2 => "H. Stjernman" 3 => "M. Olin" 4 => "M. Hansson" 5 => "J. Sjövall" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2796.2007.01814.x" "Revista" => array:6 [ "tituloSerie" => "J Intern Med" "fecha" => "2007" "volumen" => "262" "paginaInicial" => "254" "paginaFinal" => "262" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17645593" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0085" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Variable clinical spectrum of the most common inborn error of bile acid metabolism – 3beta-hydroxy-Delta 5-C27-steroid dehydrogenase deficiency" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "P. Subramaniam" 1 => "P.T. Clayton" 2 => "B.C. Portmann" 3 => "G. Mieli-Vergani" 4 => "N. Hadzić" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MPG.0b013e3181b47b34" "Revista" => array:6 [ "tituloSerie" => "J Pediatr Gastroenterol Nutr" "fecha" => "2010" "volumen" => "50" "paginaInicial" => "61" "paginaFinal" => "66" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19915491" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0090" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Defects in bile acid biosynthesis – diagnosis and treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K.D. Setchell" 1 => "J.E. Heubi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.mpg.0000226386.79483.7b" "Revista" => array:7 [ "tituloSerie" => "J Pediatr Gastroenterol Nutr" "fecha" => "2006" "volumen" => "43" "numero" => "Suppl. 1" "paginaInicial" => "S17" "paginaFinal" => "S22" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16819396" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0095" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Disorders of bile acid synthesis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P.T. Clayton" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10545-010-9259-3" "Revista" => array:6 [ "tituloSerie" => "J Inherit Metab Dis" "fecha" => "2011" "volumen" => "34" "paginaInicial" => "593" "paginaFinal" => "604" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21229319" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0100" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Oral cholic acid for hereditary defects of primary bile acid synthesis: a safe and effective long-term therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Gonzales" 1 => "M.F. Gerhardt" 2 => "M. Fabre" 3 => "K.D. Setchell" 4 => "A. Davit-Spraul" 5 => "I. 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ISSN: 2387-0206

Launched in 1943, Medicina Clínica is a fortnightly journal aimed at the promotion of clinical research and practice among internal medicine and other specialists. The key characteristics of Medicina Clínica are the scientific and methodological rigor of its manuscripts, the topicality of its contents, and, especially, its practical focus with highly useful information for clinical practice. Medicina Clínica is predominantly interested in publishing original research manuscripts, which are rigorously selected according to their quality, originality, and interest, and also in continued medical education-oriented manuscripts, which are commissioned by the journal to relevant authors (Editorials, Reviews, and Diagnosis and Treatment). These manuscripts contain updated topics with a major clinical or conceptual relevance in modern medicine. The journal adheres to the standards of academic research publications in all aspects including peer-review and ethical principles. Medicina Clínica is included in the General and Internal Medicine category of Thomson Reuters.

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Current Contents/Clinical Medicine, Journal Citation Reports, SCI-Expanded, Index Medicus/Medline, Excerpta Medica/EMBASE, IBECS, IME, MEDES, PASCAL, SCOPUS, SciVerse ScienceDirect

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Impact factor

The Impact Factor measures the average number of citations received in a particular year by papers published in the journal during the two preceding years.

© Clarivate Analytics, Journal Citation Reports 2022

Impact factor 2023

2.6

Citescore

CiteScore measures average citations received per document published.

Citescore 2023

3.1

SJR

SRJ is a prestige metric based on the idea that not all citations are the same. SJR uses a similar algorithm as the Google page rank; it provides a quantitative and qualitative measure of the journal's impact.

SJR 2023

0.371

SNIP

SNIP measures contextual citation impact by wighting citations based on the total number of citations in a subject field.

SNIP 2023

0.511

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Journal Information

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Vol. 145. Issue 12.

Pages e39-e40 (December 2015)

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