Medical Care

Early diagnosis of cerebrotendinous xanthomatosis (CTX) is imperative because it is a treatable disease. This early diagnosis depends on recognition of early signs and symptoms, specifically the combination of diarrhea and cataracts along with personal or family history of infantile hepatitis, prolonged jaundice, or early infantile death.

Surgical Care

Cataract repair may be indicated. Surgical xanthoma removal is not recommended. Liver transplantation has been reported in patients with end-stage liver disease, although details are not available at the time of this writing.^[73]

Consultations

Consultation with the following may be indicated:

Gastroenterologist
Ophthalmologist
Metabolic and genetic disease specialist
Developmental specialist
Neurologist
Orthopedist
Cardiologist
Lipid disorder specialist

Diet

A diet low in cholestanol containing foods (eg, egg yolk, butter, cheddar cheese) can significantly reduce plasma cholestanol and cholesterol levels; however, true clinical benefit is not seen unless pharmacologic therapy is also started. Dietary restriction is probably not necessary if pharmacologic treatment is commenced (see below).

Prevention

Therapy with chenodeoxycholic acid (CDCA) can halt and reverse symptoms of the illness, including GI and neurologic complications.

Long-Term Monitoring

The annual examination in patients with cerebrotendinous xanthomatosis (CTX) should consist of the following:^[7]

Neurologic and neuropsychologic evaluation
Cholestanol plasma concentration assessment
Brain MRI in selected cases
Echocardiography when indicated
Bone mineral density assessment when indicated

Medication

Salen G, Steiner RD. Epidemiology, diagnosis, and treatment of cerebrotendinous xanthomatosis (CTX). J Inherit Metab Dis. 2017 Nov. 40 (6):771-781. [Medline].
Van Bogaert L, Scherer HJ, Epstein E. Une forme cerebrale de la cholesterinose generalisee [dissertation/master's thesis]. Paris: Masson et Cie. 1937.
Van Bogaert L. [The framework of the xanthomatoses and their different types. 2. Secondary xanthomatoses.]. Rev Med Liege. 1962. 17:433-43.
Menkes JH, Schimschock JR, Swanson PD. Cerebrotendinous xanthomatosis. The storage of cholestanol within the nervous system. Arch Neurol. 1968 Jul. 19(1):47-53. [Medline].
Salen G. Cholestanol deposition in cerebrotendinous xanthomatosis. A possible mechanism. Ann Intern Med. 1971 Dec. 75(6):843-51. [Medline].
Salen G, Meriwether TW, Nicolau G. Chenodeoxycholic acid inhibits increased cholesterol and cholestanol synthesis in patients with cerebrotendinous xanthomatosis. Biochem Med. 1975 Sep. 14(1):57-74. [Medline].
Berginer VM, Salen G, Shefer S. Long-term treatment of cerebrotendinous xanthomatosis with chenodeoxycholic acid. N Engl J Med. 1984 Dec 27. 311(26):1649-52. [Medline].
Oftebro H, Björkhem I, Skrede S, Schreiner A, Pederson JI. Cerebrotendinous xanthomatosis: a defect in mitochondrial 26-hydroxylation required for normal biosynthesis of cholic acid. J Clin Invest. 1980 Jun. 65(6):1418-30. [Medline]. [Full Text].
Clayton PT, Verrips A, Sistermans E, Mann A, Mieli-Vergani G, Wevers R. Mutations in the sterol 27-hydroxylase gene (CYP27A) cause hepatitis of infancy as well as cerebrotendinous xanthomatosis. J Inherit Metab Dis. 2002 Oct. 25(6):501-13. [Medline].
Gallus GN, Dotti MT, Federico A. Clinical and molecular diagnosis of cerebrotendinous xanthomatosis with a review of the mutations in the CYP27A1 gene. Neurol Sci. 2006 Jun. 27(2):143-9. [Medline].
Sugama S, Kimura A, Chen W, et al. Frontal lobe dementia with abnormal cholesterol metabolism and heterozygous mutation in sterol 27-hydroxylase gene (CYP27). J Inherit Metab Dis. 2001 Jun. 24(3):379-92. [Medline].
Skrede S, Björkhem I, Buchmann MS, Hopen G, Fausa O. A novel pathway for biosynthesis of cholestanol with 7 alpha-hydroxylated C27-steroids as intermediates, and its importance for the accumulation of cholestanol in cerebrotendinous xanthomatosis. J Clin Invest. 1985 Feb. 75(2):448-55. [Medline].
Panzenboeck U, Andersson U, Hansson M, et al. On the mechanism of cerebral accumulation of cholestanol in patients with cerebrotendinous xanthomatosis. J Lipid Res. 2007 May. 48(5):1167-74. [Medline].
Bhattacharyya AK, Lin DS, Connor WE. Cholestanol metabolism in patients with cerebrotendinous xanthomatosis: absorption, turnover, and tissue deposition. J Lipid Res. 2007 Jan. 48(1):185-92. [Medline].
Guerrera S, Stromillo ML, Mignarri A, Battaglini M, Marino S, Di Perri C. Clinical relevance of brain volume changes in patients with cerebrotendinous xanthomatosis. J Neurol Neurosurg Psychiatry. 2010 Nov. 81(11):1189-93. [Medline].
Lorincz MT, Rainier S, Thomas D, Fink JK. Cerebrotendinous xanthomatosis: possible higher prevalence than previously recognized. Arch Neurol. 2005 Sep. 62(9):1459-63. [Medline].
Falik-Zaccai TC, Kfir N, Frenkel P, et al. Population screening in a Druze community: the challenge and the reward. Genet Med. 2008 Dec. 10(12):903-9. [Medline].
Pilo-de-la-Fuente B, Jimenez-Escrig A, Lorenzo JR, Pardo J, Arias M, Ares-Luque A. Cerebrotendinous xanthomatosis in Spain: clinical, prognostic, and genetic survey. Eur J Neurol. 2011 Oct. 18(10):1203-11. [Medline].
Sekijima Y, Koyama S, Yoshinaga T, Koinuma M, Inaba Y. Nationwide survey on cerebrotendinous xanthomatosis in Japan. J Hum Genet. 2018 Mar. 63 (3):271-280. [Medline].
Zlotogora J. The molecular basis of autosomal recessive diseases among the Arabs and Druze in Israel. Hum Genet. 2010 Nov. 128(5):473-9. [Medline].
Appadurai V, DeBarber A, Chiang PW, Patel SB, Steiner RD, Tyler C, et al. Apparent underdiagnosis of Cerebrotendinous Xanthomatosis revealed by analysis of ~60,000 human exomes. Mol Genet Metab. 2015 Dec. 116 (4):298-304. [Medline].
Leitersdorf E, Safadi R, Meiner V, et al. Cerebrotendinous xanthomatosis in the Israeli Druze: molecular genetics and phenotypic characteristics. Am J Hum Genet. 1994 Nov. 55(5):907-15. [Medline].
Mignarri A, Gallus GN, Dotti MT, Federico A. A suspicion index for early diagnosis and treatment of cerebrotendinous xanthomatosis. J Inherit Metab Dis. 2014. Epub ahead of print. [Full Text].
von Bahr S, Bjorkhem I, Van't Hooft F, et al. Mutation in the sterol 27-hydroxylase gene associated with fatal cholestasis in infancy. J Pediatr Gastroenterol Nutr. 2005 Apr. 40(4):481-6. [Medline].
Moghadasian MH, Salen G, Frohlich JJ, Scudamore CH. Cerebrotendinous xanthomatosis: a rare disease with diverse manifestations. Arch Neurol. 2002 Apr. 59(4):527-9. [Medline].
Cruysberg JR, Wevers RA, Tolboom JJ. Juvenile cataract associated with chronic diarrhea in pediatric cerebrotendinous xanthomatosis. Am J Ophthalmol. 1991 Nov 15. 112(5):606-7. [Medline].
Cruysberg JR, Wevers RA, van Engelen BG, Pinckers A, van Spreeken A, Tolboom JJ. Ocular and systemic manifestations of cerebrotendinous xanthomatosis. Am J Ophthalmol. 1995 Nov. 120(5):597-604. [Medline].
Dotti MT, Rufa A, Federico A. Cerebrotendinous xanthomatosis: heterogeneity of clinical phenotype with evidence of previously undescribed ophthalmological findings. J Inherit Metab Dis. 2001 Dec. 24(7):696-706. [Medline].
Monson DM, DeBarber AE, Bock CJ, Anadiotis G, Merkens LS, Steiner RD, et al. Cerebrotendinous xanthomatosis: a treatable disease with juvenile cataracts as a presenting sign. Arch Ophthalmol. 2011 Aug. 129(8):1087-8. [Medline].
Guyant-Marechal L, Verrips A, Girard C, et al. Unusual cerebrotendinous xanthomatosis with fronto-temporal dementia phenotype. Am J Med Genet A. 2005 Dec 1. 139A(2):114-7. [Medline].
Khan AO, Aldahmesh MA, Mohamed JY, Alkuraya FS. Juvenile cataract morphology in 3 siblings not yet diagnosed with cerebrotendinous xanthomatosis. Ophthalmology. 2013 May. 120(5):956-60. [Medline].
Huijgen R, Stork AD, Defesche JC, Peter J, Alonso R, Cuevas A, et al. Extreme xanthomatosis in patients with both familial hypercholesterolemia and cerebrotendinous xanthomatosis. Clin Genet. 2012 Jan. 81(1):24-8. [Medline].
Koyama S, Kawanami T, Tanji H, Arawaka S, Wada M, Saito N, et al. A case of cerebrotendinous xanthomatosis presenting with epilepsy as an initial symptom with a novel V413D mutation in the CYP27A1 gene. Clin Neurol Neurosurg. 2012 Feb 13. [Medline].
Okuma H, Kitagawa Y, Tokuoka K, Takagi S. Cerebrotendinous xanthomatosis with cerebellar ataxia as the chief symptom. Intern Med. 2007. 46(15):1259-61. [Medline].
Bordia S, Saifee AA. Cerebrotendinous xanthomatosis with oromandibular dyskinesia. Neurol India. 2003 Dec. 51(4):556-8. [Medline].
Dotti MT, Federico A, Garuti R, Calandra S. Cerebrotendinous xanthomatosis with predominant parkinsonian syndrome: further confirmation of the clinical heterogeneity. Mov Disord. 2000 Sep. 15(5):1017-9. [Medline].
Dotti MT, Manneschi L, Federico A. Mitochondrial enzyme deficiency in cerebrotendinous xanthomatosis. J Neurol Sci. 1995 Apr. 129(2):106-8. [Medline].
Gong JY, Setchell KDR, Zhao J, Zhang W, Wolfe B, Lu Y, et al. Severe Neonatal Cholestasis in Cerebrotendinous Xanthomatosis: Genetics, Immunostaining, Mass Spectrometry. J Pediatr Gastroenterol Nutr. 2017 Nov. 65 (5):561-568. [Medline].
Fujiyama J, Kuriyama M, Arima S, et al. Atherogenic risk factors in cerebrotendinous xanthomatosis. Clin Chim Acta. 1991 Aug 15. 200(1):1-11. [Medline].
Frih-Ayed M, Boughammoura-Bouatay A, Ben Hamda K, Chebel S, Ben Farhat M. [Hypertrophy of the atrial septum in the cerebrotendinous xanthomatosis]. Rev Med Interne. 2005 Dec. 26(12):992-3. [Medline].
Dotti MT, Mondillo S, Plewnia K, Agricola E, Federico A. Cerebrotendinous xanthomatosis: evidence of lipomatous hypertrophy of the atrial septum. J Neurol. 1998 Nov. 245(11):723-6. [Medline].
Berginer VM, Shany S, Alkalay D, et al. Osteoporosis and increased bone fractures in cerebrotendinous xanthomatosis. Metabolism. 1993 Jan. 42(1):69-74. [Medline].
Kawabata M, Kuriyama M, Mori S, Sakashita I, Osame M. Pulmonary manifestations in cerebrotendinous xanthomatosis. Intern Med. 1998 Nov. 37(11):922-6. [Medline].
Idouji K, Kuriyama M, Fujiyama J, Osame M, Hoshita T. [Hypothyroidism with increased serum levels of cholestanol and bile alcohol--analogous symptoms to cerebrotendinous xanthomatosis]. Rinsho Shinkeigaku. 1991 Apr. 31(4):402-6. [Medline].
Matsumoto M, Kabashima N, Serino R, et al. [Cerebrotendinous xanthomatosis with minimal change nephrotic syndrome]. Nippon Naika Gakkai Zasshi. 2007 Jan 10. 96(1):150-2. [Medline].
Dotti MT, Salen G, Federico A. Cerebrotendinous xanthomatosis as a multisystem disease mimicking premature ageing. Dev Neurosci. 1991. 13(4-5):371-6. [Medline].
Hansson M, Olin M, Floren CH, et al. Unique patient with cerebrotendinous xanthomatosis. Evidence for presence of a defect in a gene that is not identical to sterol 27-hydroxylase. J Intern Med. 2007 May. 261(5):504-10. [Medline].
Diekstra FP, Saris CG, van Rheenen W, Franke L, Jansen RC, van Es MA. Mapping of gene expression reveals CYP27A1 as a susceptibility gene for sporadic ALS. PLoS One. 2012. 7(4):e35333. [Medline].
Verrips A, van Engelen BG, Wevers RA, et al. Presence of diarrhea and absence of tendon xanthomas in patients with cerebrotendinous xanthomatosis. Arch Neurol. 2000 Apr. 57(4):520-4. [Medline].
de Sain-van der Velden MG, Verrips A, Prinsen BH, de Barse M, Berger R, Visser G. Elevated cholesterol precursors other than cholestanol can also be a hallmark for CTX. J Inherit Metab Dis. 2008 Dec. 31 Suppl 2:S387-93. [Medline].
DeBarber AE, Connor WE, Pappu AS, Merkens LS, Steiner RD. ESI-MS/MS quantification of 7alpha-hydroxy-4-cholesten-3-one facilitates rapid, convenient diagnostic testing for cerebrotendinous xanthomatosis. Clin Chim Acta. 2010 Jan. 411(1-2):43-8. [Medline].
Matysik S, Orsó E, Black A, Ahrens N, Schmitz G. Monitoring of 7a-hydroxy-4-cholesten-3-one during therapy of cerebrotendinous xanthomatosis: a case report. Chem Phys Lipids. 2011 Sep. 164(6):530-4. [Medline].
DeBarber AE, Luo J, Star-Weinstock M, Purkayastha S, Geraghty MT, Chiang JP. A blood test for cerebrotendinous xanthomatosis with potential for disease detection in newborns. J Lipid Res. 2014 Jan. 55(1):146-54. [Medline].
Tada H, Inaba S, Pozharitckaia D, Kawashiri MA. Prominent Tendon Xanthomas and Abdominal Aortic Aneurysm Associated with Cerebrotendinous Xanthomatosis Identified Using Whole Exome Sequencing. Intern Med. 2018 Apr 15. 57 (8):1119-1122. [Medline].
Egestad B, Pettersson P, Skrede S, Sjövall J. Fast atom bombardment mass spectrometry in the diagnosis of cerebrotendinous xanthomatosis. Scand J Clin Lab Invest. 1985 Sep. 45(5):443-6. [Medline].
Haas D, Gan-Schreier H, Langhans CD, Rohrer T, Engelmann G, Heverin M. Differential diagnosis in patients with suspected bile acid synthesis defects. World J Gastroenterol. 2012 Mar 14. 18(10):1067-76. [Medline].
Vaz FM, Bootsma AH, Kulik W, Verrips A, Wevers RA, Schielen PC, et al. A newborn screening method for cerebrotendinous xanthomatosis using bile alcohol glucuronides and metabolite ratios. J Lipid Res. 2017 May. 58 (5):1002-1007. [Medline].
Beppu T, Seyama Y, Kasama T, Serizawa S, Yamakawa T. Serum bile acid profiles in cerebrotendinous xanthomatosis. Clin Chim Acta. 1982 Feb 5. 118(2-3):167-75. [Medline].
Salen G, Batta AK, Tint GS, Shefer S. Comparative effects of lovastatin and chenodeoxycholic acid on plasma cholestanol levels and abnormal bile acid metabolism in cerebrotendinous xanthomatosis. Metabolism. 1994 Aug. 43(8):1018-22. [Medline].
Salen G, Zaki FG, Sabesin S, Boehme D, Shefer S, Mosbach EH. Intrahepatic pigment and crystal forms in patients with cerebrotendinous xanthomatosis (CTX). Gastroenterology. 1978 Jan. 74(1):82-9. [Medline].
Mondelli M, Sicurelli F, Scarpini C, Dotti MT, Federico A. Cerebrotendinous xanthomatosis: 11-year treatment with chenodeoxycholic acid in five patients. An electrophysiological study. J Neurol Sci. 2001 Sep 15. 190(1-2):29-33. [Medline].
Barkhof F, Verrips A, Wesseling P, et al. Cerebrotendinous xanthomatosis: the spectrum of imaging findings and the correlation with neuropathologic findings. Radiology. 2000 Dec. 217(3):869-76. [Medline].
De Stefano N, Dotti MT, Mortilla M, Federico A. Magnetic resonance imaging and spectroscopic changes in brains of patients with cerebrotendinous xanthomatosis. Brain. 2001 Jan. 124:121-31. [Medline].
Mignarri A, Dotti MT, Federico A, De Stefano N, Battaglini M, Grazzini I, et al. The spectrum of magnetic resonance findings in cerebrotendinous xanthomatosis: redefinition and evidence of new markers of disease progression. J Neurol. 2017 May. 264 (5):862-874. [Medline].
Androdias G, Vukusic S, Gignoux L, Boespflug-Tanguy O, Acquaviva C, Zabot MT, et al. Leukodystrophy with a cerebellar cystic aspect and intracranial atherosclerosis: an atypical presentation of cerebrotendinous xanthomatosis. J Neurol. 2012 Feb. 259(2):364-6. [Medline].
Catarino CB, Vollmar C, Küpper C, Seelos K, Gallenmüller C, Bartkiewicz J, et al. Brain diffusion tensor imaging changes in cerebrotendinous xanthomatosis reversed with treatment. J Neurol. 2018 Feb. 265 (2):388-393. [Medline].
Verrips A, Nijeholt GJ, Barkhof F, et al. Spinal xanthomatosis: a variant of cerebrotendinous xanthomatosis. Brain. 1999 Aug. 122 (Pt 8):1589-95. [Medline].
Inglese M, DeStefano N, Pagani E, et al. Quantification of brain damage in cerebrotendinous xanthomatosis with magnetization transfer MR imaging. AJNR Am J Neuroradiol. 2003 Mar. 24(3):495-500. [Medline].
Vaz FM, Bootsma AH, Kulik W, Verrips A, Wevers RA, Schielen PC, et al. A newborn screening method for cerebrotendinous xanthomatosis using bile alcohol glucuronides and metabolite ratios. J Lipid Res. 2017 May. 58 (5):1002-1007. [Medline].
Bleyle L, Huidekoper HH, Vaz FM, Singh R, Steiner RD, DeBarber AE. Update on newborn dried bloodspot testing for cerebrotendinous xanthomatosis: An available high-throughput liquid-chromatography tandem mass spectrometry method. Mol Genet Metab Rep. 2016 Jun. 7:11-5. [Medline].
Pilo B, de Blas G, Sobrido MJ, Navarro C, Grandas F, Barrero FJ. Neurophysiological study in cerebrotendinous xanthomatosis. Muscle Nerve. 2011 Apr. 43(4):531-6. [Medline].
Pierre G, Setchell K, Blyth J, Preece MA, Chakrapani A, McKiernan P. Prospective treatment of cerebrotendinous xanthomatosis with cholic acid therapy. J Inherit Metab Dis. 2008 Dec. 31 Suppl 2:S241-5. [Medline].
Shen CH, Wang ZX. Liver transplantation due to cerebrotendinous xanthomatosis end-stage liver disease. World J Pediatr. 2018 Aug. 14 (4):414-415. [Medline].
Dotti MT, Lütjohann D, von Bergmann K, Federico A. Normalisation of serum cholestanol concentration in a patient with cerebrotendinous xanthomatosis by combined treatment with chenodeoxycholic acid, simvastatin and LDL apheresis. Neurol Sci. 2004 Oct. 25(4):185-91. [Medline].
Batta AK, Salen G, Tint GS. Hydrophilic 7 beta-hydroxy bile acids, lovastatin, and cholestyramine are ineffective in the treatment of cerebrotendinous xanthomatosis. Metabolism. 2004 May. 53(5):556-62. [Medline].
Leitersdorf E, Bjorkhem I, Muri Boberg K. Inborn errors in bile acid biosynthesis and storage of sterols other than cholesterol. Scriver. Metabolic and Molecular Bases of Inherited Diseases. McGraw Hill; 2006. [Full Text].
Szlago M, Gallus GN, Schenone A, Patiño ME, Sfaelo Z, Rufa A, et al. The first cerebrotendinous xanthomatosis family from Argentina: a new mutation in CYP27A1 gene. Neurology. 2008 Jan 29. 70(5):402-4. [Medline].
Yahalom G, Tsabari R, Molshatzki N, Ephraty L, Cohen H, Hassin-Baer S. Neurological outcome in cerebrotendinous xanthomatosis treated with chenodeoxycholic acid: early versus late diagnosis. Clin Neuropharmacol. 2013 May-Jun. 36(3):78-83. [Medline].
Alhariri A, Hamilton K, Oza V, Cordoro K, Sobreira NL, Malloy M, et al. Clinical report: A patient with a late diagnosis of cerebrotendinous xanthomatosis and a response to treatment. Am J Med Genet A. 2017 Aug. 173 (8):2275-2279. [Medline].
Tibrewal S, Duell PB, DeBarber AE, Loh AR. Cerebrotendinous xanthomatosis: early diagnosis on the basis of juvenile cataracts. J AAPOS. 2017 Dec. 21 (6):505-507. [Medline].
Huidekoper HH, Vaz FM, Verrips A, Bosch AM. Hepatotoxicity due to chenodeoxycholic acid supplementation in an infant with cerebrotendinous xanthomatosis: implications for treatment. Eur J Pediatr. 2016 Jan. 175 (1):143-6. [Medline].
Bartholdi D, Zumsteg D, Verrips A, et al. Spinal phenotype of cerebrotendinous xanthomatosis--a pitfall in the diagnosis of multiple sclerosis. J Neurol. 2004 Jan. 251(1):105-7. [Medline].
Cholbam (cholic acid) [package insert]. Baltimore, MD: Asklepion Pharmaceuticals LLC. 2015 Mar. Available at [Full Text].
Federico A, Dotti MT, Volpi N. Muscle mitochondrial changes in cerebrotendinous xanthomatosis. Ann Neurol. 1991 Nov. 30(5):734-5. [Medline].
Mehta BP, Shmerling RH. Teaching neuroimage: cerebrotendinous xanthomatosis. Neurology. 2008 Jul 8. 71(2):e4. [Medline].
Mondelli M, Rossi A, Scarpini C, Dotti MT, Federico A. Evoked potentials in cerebrotendinous xanthomatosis and effect induced by chenodeoxycholic acid. Arch Neurol. 1992 May. 49(5):469-75. [Medline].
U.S. Food and Drug Administration (press release). FDA approves Cholbam to treat rare bile acid synthesis disorders. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm438572.htm. Accessed: 2015 Mar 17.
DeBarber AE, Luo J, Giugliani R, Souza CF, Chiang JP, Merkens LS, et al. A useful multi-analyte blood test for cerebrotendinous xanthomatosis. Clin Biochem. 2014 Jun. 47 (9):860-3. [Medline].

Media Gallery

Sixteen-year-old male with cerebrotendinous xanthomatosis. Note the xanthomas on his knuckles.
Sixteen-year-old male with cerebrotendinous xanthomatosis.
Xanthomas of the Achilles tendon. Photo courtesy of William Connor, MD, Oregon Health and Science University.
Xanthomas on the knees in a patient with cerebrotendinous xanthomatosis. Photo courtesy of William Connor, MD, Oregon Health and Science University.

of 4

Author

Robert D Steiner, MD Clinical Professor, University of Wisconsin School of Medicine and Public Health; Editor-in-Chief, Genetics in Medicine; Chief Medical Officer, PreventionGenetics

Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics and Genomics, American Society of Human Genetics, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: PreventionGenetics, Wisconsin, American College of Medical Genetics, Acer Therapeutics; Raptor, Retrophin; Censa Pharma; Biomarin; PreventionGenetics, Best Doctors, Health Advances, Precision for Health, E-scape Bio, PTC Therapeutics, CTX Alliance, Aeglea Serve(d) as a speaker or a member of a speakers bureau for: France Foundation, Medscape Received research grant from: Alexion Received income in an amount equal to or greater than $250 from: PreventionGenetics, State of Wisconsin, MCHS, Acer Therapeutics; Retrophin; Raptor Pharma; Censa Pharma; Biomarin; Prevention Genetics, E-Scape Bio, Best Doctors, Health Advances, Precision for Value, France Foundation, Medscape, PTC Therapeutics, Aeglea Travel Support for: Pfizer.

Coauthor(s)

Peter R Baker, II, MD, FAAP, FACMG Assistant Professor, Department of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado School of Medicine

Peter R Baker, II, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, Society for Inherited Metabolic Disorders

Disclosure: Nothing to disclose.

Andrea E DeBarber, PhD Research Assistant Professor, Department of Physiology and Pharmacology, Associate Director, Bioanalytical Shared Resource Facility, Oregon Health and Science University; Director, Bioanalytical MS Facility, Portland State University

Andrea E DeBarber, PhD is a member of the following medical societies: American Chemical Society, American Society for Mass Spectrometry

Disclosure: Received research grant from: Retrophin, Inc, US distributor of Chenodal (chenodeoxycholic acid) Received income in an amount equal to or greater than $250 from: Retrophin, Inc, US distributor of Chenodal (chenodeoxycholic acid).

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Acknowledgements

The authors would like to thank Matthias C. Kurth, MD, PhD, for review of the manuscript.