DNA mutational analysis revealed that the child was homozygous for a novel E64K mutation and that his mother and father were heterozygous for the novel E64K mutation. Potential causes
Smoking: Recent studies suggest that smoking can lead to marginal biotin deficiency because it speeds up biotin catabolism (especially in women). Excessive alcohol consumption
Excessive consumption of antidiuretics or inadequate levels of antidiuretic hormone
Intestinal malabsorption caused by short bowel syndrome

Biochemistry
Biotin is a coenzyme for five carboxylases in the human body (propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, pyruvate carboxylase, and 2 forms of acetyl-CoA carboxylase.) Therefore, biotin is essential for amino acid catabolism, gluconeogenesis, and fatty acid metabolism. Biotin is also necessary for gene stability because it is covalently attached to histones. Biotinylated histones play a role in repression of transposable elements and some genes. Normally, the amount of biotin in the body is regulated by dietary intake, biotin transporters (monocarboxylate transporter 1 and sodium-dependent multivitamin transporter), peptidyl hydrolase biotinidase (BTD), and the protein ligase holocarboxylase synthetase. When any of these regulatory factors are inhibited, biotin deficiency could occur. Diagnosis
The most reliable and commonly used methods for determining biotin status in the body are:

excretion of 3-hydroxyisovaleric acid and biotin in urine
activity of propionyl-CoA carboxylase in lymphocytes

Treatment
In the United States, biotin supplements are readily available without a prescription in amounts ranging from 300 to 10,000 micrograms (30 micrograms is identified as Adequate Intake). Epidemiology
Since biotin is present in many foods at low concentrations, deficiency is rare except in locations where malnourishment is very common.
Diarrhea
Irinotecan-associated diarrhea is severe and clinically significant, sometimes leading to severe dehydration requiring hospitalization or intensive care unit admission. This side-effect is managed with the aggressive use of antidiarrheals such as loperamide or atropine with the first loose bowel movement. Immunosuppression
The immune system is adversely impacted by irinotecan. This is reflected in – sometimes dramatically – lowered white blood cell counts in the blood, in particular the neutrophils. The patient may experience neutropenia (a clinically significant decrease of neutrophils in the blood). Mechanism of action
Camptothecin, one of the four major structural classifications of plant-derived anti-cancerous compounds, is a cytotoxic alkaloid which consists of a pentacyclic ring structure containing a pyrrole (3, 4 β) quinoline moiety, an S-configured lactone form, and a carboxylate form. Camptothecin is an inhibitor of topoisomerase I. Its analogue, irinotecan, is activated by hydrolysis to SN-38, and is then inactivated by glucuronidation by uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). The inhibition of topoisomerase I by the active metabolite SN-38 eventually leads to inhibition of both DNA replication and transcription.The molecular action of irinotecan occurs by trapping a subset of topoisomerase-1-DNA cleavage complexes, those with a guanine +1 in the DNA sequence. One irinotecan molecule stacks against the base pairs flanking the topoisomerase-induced cleavage site and poisons (inactivates) the topoisomerase 1 enzyme. Interactive pathway
Click on genes, proteins and metabolites below to link to respective articles. Pharmacokinetics
Administration
Irinotecan can be administrated by 30- or 90-minute intravenous infusions of either 125 mg/m2 weekly for four of every six weeks or 350 mg/m2 every three weeks.