Casefile 4: Lipoamide dehydrogenase deficiency

What a debate Inspector Zhao and Dectective CXY had!!! I have to admit they were making a lot of noise...goodness. Talking about hypoglycemia, I just found out that it can be a sign of this disease with a long long name: Lipoamide dehydrogenase deficiency(LAD). Cheem right?

LAD is a rare cause of primary lactic acidosis in children. It has been reported in about 20 patients. Patients are usually free from symptoms in the first few weeks or months of life except for inconstant episodes of HYPOGLYCEMIA (haha...here's where the word appears. See, it's linked!). Oh, by the way, it's a neonatal disease that can occur in all ages, isn't that scary? Brr...

Ok, here comes a sophistically complicatedly complex sentence. LAD is a catalytic subunit shared by three mitochondrial enzymes: pyruvate dehydrogenase (PDH), branched chain-keto acid dehydrogenase (BCKAD) and alpha-ketoglutarate dehydrogenase (alpha-KGD). Do you understand a word? I'm sure you don't, haha. That's why I, Forensic Scientist Kelly, am here to explain it specially for you.

First, Pyruvate dehydrogenase is an enzyme (E1) in the pyruvate dehydrogenase complex (PDC). It catalyses the rate-limiting reaction within the PDC. You can get all the information from the net if you don't understand.

Next, branched-chain alpha-keto acid dehydrogenase complex is a combination of enzymes responsible for the degradation of the branched chain amino acids. Examples include valine, isoleucine, and leucine (recognise these names? Ahaha...3 of the 20 amino acids we memorised). A deficiency in any of the enzymes of this complex as well as an inhibition of the complex as a whole is responsible for maple syrup urine disease.

Lastly, alphagluterate dehydrogenase is an enzyme complex most commonly known for its role in the citric acid cycle. Much like pyruvate dehydrogenase complex, this enzyme forms a complex composed of three components: E1(EC 1.2.4.2), E2(EC 2.3.1.61) and E3(EC 1.8.1.4), which use thiamine pyrophosphate, lipoic acid and NAD+ as coenzymes, respectively.

Ok, I think all these information is really confusing. Coming back to LAD...Neonatal onset with metabolic lactic acidosis, hypoglycemia, lethargy and failure to thrive can occur. Some patients are free of symptoms between acute attacks. Adult patients have also been reported with acute hepatitis, lactic acidosis and myoglobinuria, without any neurological symptoms.

So is there a way to be saved? In a way yes! Prenatal diagnosis, using molecular analyses on chorionic villous samples, is available to families in which the mutations of the genes have been identified.

Phew!!! Ok fine, i give loooooong lectures. I really have to own it to Detective CXY, haha. By the way Inspector Zhao, it is unhealthy to eat doughnuts all the time! Remember the article on trans fats? Yeah...doughnuts are especially rich in trans fats! Be mindful of your health! Haha...

By Forensic Scientist Kelly
Kelly Ng (30)