Genetic Medicine

Gilbert Syndrome

Spoiler alert! Avoid your eyes if you haven’t seen Kung Fu Panda before. Return to the dark cave from whence you came.

Just as Oogway becomes dust, red blood cells die and puff out bilirubin. This is shunted to the liver, which does the necessary cleaning job, removing the unwanted bilirubin from the bloodstream through glucuronidation. This forms conjugated bilirubin. After Liver Kondo has done its thing, the product is pumped out to the intestines, then away it goes.

Gilbert Syndrome is an autosomal recessive condition where the UGT1A1 gene is most commonly affected. This gene makes an important enzyme for the bilirubin detoxifying process, so the result is raised bilirubin. Specifically, it would be unconjugated hyperbilirubinaemia and possibly jaundice, often not requiring treatment except in stress-affected situations.

References

  1. Mayo Clinic (2025). Gilbert syndrome. [online] Mayo Clinic. Available at: https://www.mayoclinic.org/diseases-conditions/gilberts-syndrome/symptoms-causes/syc-20372811.
  2. Grant LM, Faust TW, Thoguluva Chandrasekar V, et al. Gilbert Syndrome. [Updated 2024 Oct 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470200/.
  3. Hamoud AR, Weaver L, Stec DE, Hinds TD Jr. Bilirubin in the Liver-Gut Signaling Axis. Trends Endocrinol Metab. 2018 Mar;29(3):140-150. doi: 10.1016/j.tem.2018.01.002. Epub 2018 Feb 3. PMID: 29409713; PMCID: PMC5831340. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC5831340/.
  4. MedlinePlus (n.d.). UGT1A1 gene: MedlinePlus Genetics. [online] medlineplus.gov. Available at: https://medlineplus.gov/genetics/gene/ugt1a1/.

Xerox In Biology

Circular definitions are a trap. It’s good to avoid traps.

Hence, in simple terms, here are some useful explanations.

Genes are the computer coding for people, because we all know people are actually robots. (Click. Whirr. This is a joke.)

A genotype is the total computer code print-out for a person. It’s relevant to inheritable diseases. A disease is a state of poor health, by the way. It has to be significantly abnormal enough for it to be classed as diagnosable, given these things are based on artificial cut-offs. They can be somewhat arbitrary, but generally there’s a reasonable basis underneath them.

A phenotype is the outside casing of the computer product, which is distinct from its wiring inside. It represents how matters surface in the material world.

A phenocopy is a materialised appearance of things that doesn’t actually have the relevant genotype. That is, it looks like that computer coding output, but the computer coding is different from what it’s expected to be. It resembles a syndrome but without the genetic basis for it.

The phenocopy situation can occur in Huntington’s disease, where the autosomal dominant CAG-repeater mutation isn’t apparent but similar clinical manifestations arise.

References

  1. Moore RC, Xiang F, Monaghan J, Han D, Zhang Z, Edström L, Anvret M, Prusiner SB. Huntington disease phenocopy is a familial prion disease. Am J Hum Genet. 2001 Dec;69(6):1385-8. doi: 10.1086/324414. Epub 2001 Oct 9. PMID: 11593450; PMCID: PMC1235549.

Partial Chromosome 15 Deletions

Angelman Syndrome

  • Maternal segment of chromosome 15 deleted
  • Angelman because there is no female part
    • Maternal genetic deletion
  • Happy and flappy

Prader-Willi Syndrome

  • Paternal segment of chromosome 15 deleted
  • Prader-Willi is lacking the paternal part
    • Paternal genetic deletion
  • Fat, dumb, weak and infertile

References

  1. Genetics Home Reference. (2018). Angelman syndrome. [online] Available at: https://ghr.nlm.nih.gov/condition/angelman-syndrome [Accessed 24 Apr. 2018].
  2. Genetics Home Reference. (2018). Prader-Willi syndrome. [online] Available at: https://ghr.nlm.nih.gov/condition/prader-willi-syndrome [Accessed 24 Apr. 2018].

Three Major Trisomy Disorders

Trisomy 13: Patau syndrome

Trisomy 18: Edward syndrome

Trisomy 21: Down syndrome

Informative, right? Not yet! The real meat, or pseudo-meat if you’re not of a carnivorous sentiment, is in the memorising.

Memory Aids

Arrange these trisomies in order of increasing number: 13, 18, 21.

Then the mnemonic you need is: PED. As in pediatrics! As in children! Which is the patient demographic to whom these congenital trisomies relate.

The prevalence follows a similar trend; Patau syndrome is the most life-threatening but least common and those with Edward syndrome can live a tiny bit longer but not much so, while Down syndrome is more compatible with life and the most common of these three conditions.

Screening Tests

Down syndrome is famously detected through a first trimester screening test:

  • Free beta-hCG
    • Blood test
  • PAPP-A
    • Blood test
  • Nuchal translucency scan
    • Measures nuchal fold thickness, as this is greater in Down syndrome

NIPT is another option. It’s non-invasive prenatal testing that uses the mother’s blood.

Diagnostic Tests

The more definitive options are:

  • CVS
    • Done earlier but presents greater risk to the foetus, because it’s about chopping off a bit of the chorionic villus
  • Amniocentesis
    • Done later at half the risk of CVS, with the downside of the parents having to find out further into the pregnancy compared to CVS

References

  1. The University of Chicago Pediatrics Clerkship. (2018). Trisomy 18 (Edwards), Trisomy 13 (Patau). [online] Available at: https://pedclerk.bsd.uchicago.edu/page/trisomy-18-edwards-trisomy-13-patau [Accessed 31 Mar. 2018].
  2. Pregnancy, Birth and Baby. (2018). Screening for Down syndrome. [online] Available at: https://www.pregnancybirthbaby.org.au/screening-for-down-syndrome [Accessed 31 Mar. 2018].
  3. BabyCenter Australia. (2018). Screening for Down syndrome. [online] Available at: https://www.babycenter.com.au/a1487/screening-for-down-syndrome [Accessed 31 Mar. 2018].

Glycogen Storage Disease

GSD is a genetic disease characterised by missing enzymes. Inheritance is typically autosomal recessive.

GSD involves disrupted glycogen metabolism. It makes glycogen accumulate or not form properly, so the glycogen cannot be broken down into glucose or stored like normal.

Treatment can include dietary modification.

References

  1. Kinsey, A. W., & Ormsbee, M. J. (2015). The Health Impact of Nighttime Eating: Old and New Perspectives. Nutrients, 7(4), 2648–2662. http://doi.org/10.3390/nu7042648
  2. Johns Hopkins Medicine. (n.d.). Glycogen Storage Disease in Children. [online] Available at: https://www.hopkinsmedicine.org/healthlibrary/conditions/liver_biliary_and_pancreatic_disorders/glycogen_storage_disease_in_children_134,227 [Accessed 23 Jan. 2018].
  3. Cleveland Clinic. (2018). Glycogen Storage Disease. [online] Available at: https://my.clevelandclinic.org/health/diseases/15553-glycogen-storage-disease-gsd [Accessed 23 Jan. 2018].