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Teddy was diagnosed with Alagille syndrome

Teddy was diagnosed with Alagille syndrome

Teddy’s fur is scratched, scarred, and yellowing. He has deep-set eyes and a prominent chin. He has poor weight gain and growth. Teddy has Alagille syndrome (ALGS).

Like with every patient with chronic cholestatic liver disease, ALGS has impaired Teddy’s quality of life and robbed him of his childhood.1 Teddy shouldn’t have to bear it any longer.

That’s why Mirum is speaking up. We’re dedicated to raising awareness and addressing the impact cholestatic liver disease can have on patients like Teddy. In support of this commitment, we are doing our part to conduct research and help patients reclaim their childhoods.

What Is ALGS?

Alagille syndrome (ALGS) is a rare, life-threatening multisystem disease that often presents in childhood.2 With ALGS, bile ducts are abnormally narrow, malformed, and reduced in number, which leads to toxic accumulation of bile acids in the liver and, ultimately, progressive liver disease.1,3

For more information about cholestatic liver disease, visit these Resources.

ALGS is an autosomal dominant disorder caused by mutations/deletions in the1,2,4,5:

Disruptions in these genes cause defective bile duct morphogenesis and impaired angiogenesis, and abnormalities in skeletal, ocular, cardiovascular, and kidney development.6 Although 30% to 50% of individuals have an inherited pathogenic variant, the mutation occurs de novo in 50% to 70% of cases.7

ALGS affects males and
females equally
8

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The estimated incidence of ALGS is 1 in every 30,000 to 45,000 individuals8

There are currently an estimated 2500 children living with ALGS in the United States.
There are currently
an estimated
2500 children
living with ALGS in
the United States9

In patients with ALGS, multiple organs/areas may be affected, including8:

In patients with ALGS, multiple organs/areas may be affected, including In patients with ALGS, multiple organs/areas may be affected, including

Importantly, the bile duct paucity associated with ALGS leads to impaired bile flow, accumulation of bile acids in the liver and bloodstream, and cholestatic liver injury.1,10 Increased serum bile acids (sBA) lead to debilitating pruritus. This, in turn, can cause severe sleep deprivation, resulting in fatigue, a failure to thrive, and a dramatic reduction in quality of life.11,12 In approximately 15% of patients, progressive liver disease results in cirrhosis of the liver and liver failure.8 Phenotype is not a clear predictor for risk of progressive liver disease in ALGS.13

For more information about cholestatic liver disease, visit these Resources.

Signs +
Symptoms

Symptoms of Alagille syndrome (ALGS) usually appear in the first 2 years of life.14

To learn more about these symptoms and how they're impacting patients, download this comprehensive brochure.

patient
88% of patients

are affected by cholestatic pruritus—a severe, unrelenting itch. Driven by the increase in sBA, this cholestatic pruritus has been identified as the most bothersome symptom of ALGS.1,2

Additional signs and symptoms arising from chronic cholestasis in ALGS may include1,2,15:

Jaundice

Jaundice

Jaundice affects the majority of patients, presenting in 66% to 87%.

Xanthomas

Xanthomas

Xanthomas are common, affecting 30% to 42% of patients and usually appearing at a median of 20 months to 48 months of age.

Failure to thrive and growth deficiencies

Failure to thrive and growth deficiencies

Growth impairment, development delay, or failure to thrive has been reported in 50% to 87% of patients.

Diminished quality of life

Diminished quality of life

Cholestatic pruritus is associated with additional symptoms, such as skin damage, sleep problems, mood disturbances, and more.

Extrahepatic manifestations include8,15-17:

Hypovitaminosis

Hypovitaminosis

Hypovitaminosis, leading to rickets, brittle bones, and blood clotting problems.

Facial

Facial

Facial structural changes, including prominent forehead, deep-set eyes, pointed chin, and bulbous tipped nose.

Ocular

Ocular

Ocular, including posterior embryotoxon.

Vascular

Vascular

Vascular involvement, including intracranial bleeding and central nervous system (CNS) vascular malformations.

Cardiovascular

Cardiovascular

Cardiovascular issues, including peripheral pulmonary stenosis (PPS).

Skeletal

Skeletal

Skeletal abnormalities, including butterfly vertebrae.

Renal

Renal

Renal abnormalities, including renal dysplasia.

To learn more about these symptoms and how they're impacting patients, download this comprehensive brochure.

ALGS=Alagille syndrome; CNS=central nervous system; PPS=peripheral pulmonary stenosis; sBA=serum bile acid.
References: 1. Kamath BM, Stein P, Houwen RHJ, Verkade HJ. Potential of ileal bile acid transporter inhibition as a therapeutic target in Alagille syndrome and progressive familial intrahepatic cholestasis. Liver Int. 2020;40(8):1812-1822. doi:10.1111/liv.14553 2. Kamath BM, Baker A, Houwen R, Todorova L, Kerkar N. Systematic review: the epidemiology, natural history, and burden of Alagille syndrome. J Pediatr Gastroenterol Nutr. 2018;67(2):148-156. doi:10.1097/MPG.0000000000001958 3. MedlinePlus. Alagille syndrome. Accessed March 9, 2021. https://medlineplus.gov/genetics/condition/alagille-syndrome 4. Goldberg A, Mack CL. Inherited cholestatic diseases in the era of personalized medicine. Clin Liver Dis (Hoboken). 2020;15(3):105-109. doi:10.1002/cld.872 5. Kamath BM, Ye W, Goodrich NP, et al. Outcomes of childhood cholestasis in Alagille syndrome: results of a multicenter observational study. Hepatol Commun. 2020;4(3):387-398. doi:10.1002/hep4.1468 6. Verkade HJ, Bezerra JA, Davenport M, et al. Biliary atresia and other cholestatic childhood diseases: advances and future challenges. J Hepatol. 2016;65(3):631-642. doi:10.1016/j.jhep.2016.04.032 7. Spinner NB, Gilbert MA, Loomes KM, Krantz ID. Alagille syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews. Seattle (WA): University of Washington, Seattle. Published online: May 19, 2000. Updated: December 12, 2019. https://www.ncbi.nlm.nih.gov/books/NBK1273/pdf/Bookshelf_NBK1273.pdf 8. National Organization for Rare Disorders. Alagille syndrome. Accessed March 9, 2021. https://rarediseases.org/rare-diseases/alagille-syndrome/ 9. Mirum Pharmaceutical Market Research. 2020. 10. Saleh M, Kamath BM, Chitayat D. Alagille syndrome: clinical perspectives. Appl Clin Genet. 2016;9:75-82. doi:10.2147/TACG.S86420 11. Gerber L. Sleep deprivation in children: a growing public health concern. Nurs. 2014;44(4):50-54. doi:10.1097/01.NURSE.0000441881.87748.90 12. Düll MM, Kremer AE. Newer approaches to the management of pruritus in cholestatic liver disease. Curr Hepatol Rep. 2020;19:86-95. doi:10.1007/s11901-020-00517-x 13. Kamath BM, Schwarz KB, Hadzἷć N. Alagille syndrome and liver transplantation. J Pediatr Gastroenterol Nutr. 2010;50(1):11-15. doi:10.1097/MPG.0b013e3181c1601f 14. Johns Hopkins Medicine. Alagille syndrome. Accessed March 9, 2021. https://www.hopkinsmedicine.org/health/conditions-and-diseases/alagille-syndrome 15. Singh SP, Pati GK. Alagille syndrome and the liver: current insights. Euroasian J Hepatogastroenterol. 2018;8(2):140-147. doi:10.5005/jp-journals-10018-1280 16. Turnpenny PD, Ellard S. Alagille syndrome: pathogenesis, diagnosis and management. Eur J Hum Genet. 2012;20(3):251-257. doi:10.1038/ejhg.2011.181 17. Ayoub MD, Kamath BM. Alagille syndrome: diagnostic challenges and advances in management. Diagnostics (Basel). 2020;10(11):907. doi:10.3390/diagnostics10110907