Science topic

Inborn Errors of Metabolism - Science topic

Inborn errors of metabolism comprise a large class of genetic diseases involving disorders of metabolism. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances (substrates) into others (products). In most of the disorders, problems arise due to accumulation of substances which are toxic or interfere with normal function, or to the effects of reduced ability to synthesize essential compounds. Inborn errors of metabolism are now often referred to as congenital metabolic diseases or inherited metabolic diseases.
Questions related to Inborn Errors of Metabolism
  • asked a question related to Inborn Errors of Metabolism
Question
3 answers
A full-term female infant failed to gain weight and showed metabolic acidosis in the neonatal period. A physical examination at 6 months showed failure to thrive, hypotonia, small muscle mass, severe head lag, and a persistent acidosis (pH 7.0 to 7.2). Blood lactate, pyruvate, and alanine were greatly elevated. Treatment with thiamine did not alleviate the lactic acidosis. Which of the following enzymes is most likely deficient in this patient?
a) Alanine amino transferase
b) Phosphoenolpyruvate carboxy kinase
c) Pyruvate carboxylase
d) Pyruvate dehydrogenase
e) Pyruvate kinase
Relevant answer
Answer
Pyruvate carboxylase
Rationale: A biotin-dependent enzyme belonging to the ligase family that catalyzes the addition of CARBON DIOXIDE to pyruvate. It occurs in both plants and animals. Deficiency of this enzyme causes severe psychomotor retardation and ACIDOSIS, LACTIC in infants.
  • asked a question related to Inborn Errors of Metabolism
Question
7 answers
Treating children known to have metabolic disorders often includes ensuring adequate amount of calories for age and weight to avoid catabolism, that is usually by giving glucose solution 10%.
What is the long term impact of the sugary fluids on these patients?
Does it contribute to generating some degree of insulin resistance?
Can we predict the insulin resistance if so?
will HOMA-IR serve as a good predictor test?
Relevant answer
Answer
Perhaps the “ESPGHAN/ESPEN/ESPR guidelines on pediatric parenteral nutrition: Carbohydrates” and related publications provide the appropriate and practical instructions for glucose infusion in children [1]. Excessive chronic glucose infusion may lead to hyperglycemia, which leads to increased lipogenesis and adipocyte fat deposition along with subsequent hepatic steatosis, elevated hepatic VLDL triglycerides, hypercholesterolemia, and may ultimately cause insulin resistance (IR) [1]. The magnitude of this effect depends individually and is affected by pre-existing metabolic stress or disease [1]. The gold standard for determining IR is the euglycemic–hyperinsulinemic clamp technique [3]. This method is considered invasive, costly, and impractical for large samples. Despite its modest specificity and sensitivity, HOMA-IR is used as an IR surrogate and alternative index in a large number of studies, including those dealing with children [4]. Other IR indexes with varied specificity and sensitivity, as well as purposes, are available [3,4].
References:
[1] Mesotten D, Joosten K, Kempen A, et al. ESPGHAN/ESPEN/ESPR guidelines on pediatric parenteral nutrition: carbohydrates. Clinical Nutrition, 2018; xxx: 1-7. http://dx.doi.org/10.1016/ j.clnu.2018.06.947.
[2] Sanchez-Garc´ıa A, Rodr´ıguez-Gutierrez R, Mancillas-Adame L. et al. Diagnostic accuracy of the triglyceride and glucose index for insulin resistance: a systematic review. International Journal of Endocrinology, 2020; ID 4678526, 7 pages. https://doi.org/10.1155/2020/ 4678526.
[3] van der Aa Marloes P, Catherijne AJK, Anthonius dB, et al. Definition of insulin resistance affects prevalence rate in pediatric patients: a systematic review and call for consensus. Journal of Pediatric Endocrinology and Metabolism, 2017; 30(2):123-131.doi:10.1515/jpem-2016-0242.
  • asked a question related to Inborn Errors of Metabolism
Question
6 answers
For working on inborn errors of metabolism in human samples.  I have Agilent's Zorbax Eclipse Plus C18 column (4.6 X 250 mm, 5 micron) and Zorbax 300SB-C-18 column (4.6 X 250 mm, 5 micron). Can I use them in my HPLC for amino acid separation in human blood and urine samples. If so, which one will be better? 
Relevant answer
Answer
If you don't treat the sample to remove large molecular weight proteins or use a restricted access medium you will have a lot of problems. First derived from competition and second due to mass transfer effects. As I said before start with the larger pore size column and see what happens. 
  • asked a question related to Inborn Errors of Metabolism
Question
6 answers
Can someone help me find an specific Medical History format  for patients diagnosed with an inborn error of metabolism by neonatal screening or in general? Or do you work with general medical history formats?
Relevant answer
Thanks for the Information Hassan
  • asked a question related to Inborn Errors of Metabolism
Question
5 answers
I would like to do quantitative estimation of amino acids in blood sample for inborn errors of metabolism. I have a new agilent HPLC 1260 model. Can anyone provide the protocol? Thanks in advance.
Relevant answer
Answer
Not having an LC-MS system will make life a tad difficult.  For starters you will either have to derivatise AAs prior to HPLC or employ on-line post-column derivatisation so your analytes become amenable to UV detection. The alternative to avoid derivatisation is the use of an ELS detector for HPLC.  Irrespective of detection method you will have to prepre standard solutions (of single compounds as well as a compound mixture) to determine retention (elution) times for the individual AAs and to optimize chromatographic conditions to avoid total or partial peak overlap (co-elution of compounds).
  • asked a question related to Inborn Errors of Metabolism
Question
7 answers
Should I carry out a case control study or cross sectional study in case where incidence is very rare such as 1 in 1000 or so?
Relevant answer
Answer
Thanks Dr. James. This means I should do a case control study rather than going with cross sectional study. Can you plz let me know the sample size if the incidence (not prevalence) given for inborn errors of metabolism is 1 in 1000. (acc to research publications)
  • asked a question related to Inborn Errors of Metabolism
Question
4 answers
We are working out a diagnosis of MNGIE in two patient, but we seem to be unable to nail down mutation, therefore we need metabolic diagnosis. Preferably in Germany.
Relevant answer
Answer
Dr. Lynette Fairbanks at the Purine Research Laboratory,
St.Thomas' Hospital, London SE1 7EH measures TP enzyme activity in Leucocytes for MINGIE.
  • asked a question related to Inborn Errors of Metabolism
Question
9 answers
Maple syrup urine disease (MSUD) is an inherited disorder of branched-chain amino acid metabolism presenting with lifethreatening cerebral oedema in affected individuals. Treatment requires life-long dietary restriction and monitoring of branched-chain amino acids to avoid brain injury. Despite careful management, children commonly suffer metabolic decompensation in the context of catabolic stress associated with non-specific illness.
Relevant answer
Answer
In MSUD , MAIN focus is to avoid valine , leucine & isoleucine containing foods . Treatment with thiamine is remarkable in thiamine responsive type of disease.