Category Archives: Molecular Biology and Genetics

Metabolic Disorders: Part I

Annalies Corse BMedSc, BHSc, Masters Candidate (USYD).


Question anyone on the concept of metabolism, and you will surely receive responses supporting that everyone knows about it. Young children learn of its existence at school; science students worldwide study the intricate metabolic reactions of living cells and the general public speaks this technical term during social banter around food and weight. However, metabolism is a facet of human health involving far more than the breakdown of food or the production of energy. Metabolism, and the biomedical understanding of metabolic disorders is one of the five pillars of health supporting the philosophy behind the MINDD Foundation. Over a series of articles, these five pillars will be presented and discussed to help you understand the importance of each for human health, including the biomedical, nutritional and lifestyle measures to improve your own health, your family’s health and safeguarding the health of generations to come.


Research and education into the role of Metabolic disorders in Pediatric health is fundamental to the work of the MINDD Foundation. This two part article serves to explain the importance of metabolism to our overall state of health, list the conditions associated with errors in metabolism (including the cause of such errors) and what can be done to prevent the potentially devastating consequences of errors of metabolism.


Definition of Metabolism


Metabolism occurs at the cellular and even subcellular level within tiny structures known as organelles. It is usually defined and interpreted in biochemical terms, where all reactions of the metabolic system are considered together.  In the most simplistic definition, metabolism is defined as the sum total of all chemical reactions in the body. Metabolism is comprised of:


  • Anabolism: chemical reactions where substances are synthesized or ‘built up’. For example: the synthesis of hormones, new tissue and antibodies, to name a few.


  • Catabolism: chemical reactions where substances are degraded or ‘broken down’. For example: the breakdown of food for energy production and the generation of metabolic waste products such as ketones, urea and lactate to name a few.


Therefore, every single chemical reaction in your body is part of your metabolism. Every useful chemical substance your body makes for you, and every waste product generated is part of your metabolism. These metabolic reactions differ depending on which organ of the body you are looking at. For example, the reactions of thyroid metabolism are completely different from reactions in skeletal muscle; every tissue and organ has a completely different role to play and their metabolic chemical reactions reflect this. Your metabolism represents far more than just weight loss and weight gain.


Errors in Metabolism +Causes


Inborn errors of metabolism are a very large group of rare and congenital disorders of metabolism, where babies are born with a genetic defect involving a specific aspect of their metabolism. These conditions are usually inherited. Most are due to single genetic mutations, where the faulty gene leads to the production of a faulty enzyme. The faulty enzyme produced is unable to catalyze its specific chemical reaction in the body (each enzyme in the human body is highly precise and usually only facilitates one specific chemical reaction). The resulting problems are incredibly varied, depending on the gene and enzyme product involved. Some conditions can be managed well, while others can be lethal errors. Depending on the actual condition inherited, symptoms can range from acute and late-onset acute, through to progressive, generalized and permanent symptoms.


List of Conditions


There are hundreds of inherited metabolic disorders, and most are exceedingly rare. As a whole, metabolic disorders usually involve a gene/enzyme product involved in:


  • Carbohydrate metabolism: these are usually detected in infancy and cover a vast range of conditions where specific aspects of carbohydrate metabolism are impaired. Energy production in vital organs can be severely compromised. Depending on the exact problem, these conditions are often supported by dietary interventions. Some better-known examples in this category are galactosaemia, lactose intolerance and glycogen storage diseases.
  • Amino acid metabolism: these metabolic conditions involve either the synthesis of vital amino acids, or impairment of amino acid degradation. These are so many diseases in this category, however Phenylketonuria (PKU), Homocysteinuria and Maple Syrup Urine disease are some well-known examples. If a vital amino acid is not synthesized, it is unavailable for its many roles within the body. If an amino acid is not degraded properly, it can build up, causing damage to specific tissues and organs. Dietary interventions are often used to abate the effects of these diseases.
  • Organic acid metabolism: these involve the branched chain amino acids (isoleucine, leucine and valine). If a specific amino acid cannot be broken down, its build-up can lead to academia (dangerously low blood pH) and vital organ damage. Specific dietary interventions are required, and these often commence in infancy.
  • Fatty acid metabolism: many enzymes are required to break down fatty acids for energy; a problem with any one of these enzymes is known as an inborn error of lipid (fat) metabolism. Some involve carnitine (which helps transport fatty acids to your mitochondria for energy production), while others prevent correct lipid storage. Yet another vast category.
  • Mitochondrial metabolism: these have a huge array of presentations, but ultimately involve impairment of mitochondrial function and ultimately the production of energy as a whole.
  • Porphyrin metabolism: porhyrin rings are specific chemical structures found in vital substances such as haeme (predominantly found in red blood cells) and cytochromes (found in mitochondria for energy production and also in hepatic tissue for detoxification). When not synthesized or degraded properly, they are classified as metabolic diseases known as Porphyrias. It is believed that Pyrrole Disorder may belong to this category.
  • Purine and pyrimidine metabolism: purines and pyrimidine’s are essential chemicals produced by the body and contribute to the structure of DNA, RNA and energy molecules such as ATP to name just a few. Defective enzymes governing purine and pyrimidine metabolism affect the normal sequences of human DNA, meaning harmful mutations are common in this group of metabolic diseases.
  • Peroxisomal metabolism: peroxisomes are organelles involved in breaking down very long chain fatty acids for energy.
  • Steroid metabolism: human steroid hormones include oestrogen, progesterone, testosterone, cortisol, and aldosterone. All steroid hormones are derived from cholesterol. Each condition varies, depending on the exact enzyme and hormone involved. Disorders of secondary sexual characteristics, ambiguous genitalia and adrenal insufficiency all come under this category.
  • Lysosomal storage diseases. Lysosomes are organelles, and can be described as the recycling centre of the cell. Unwanted substances can be converted into useful substances for a cell by lysosomes. Metabolic disorders involving lysosomes result in the accumulation of cellular waste, leading to cellular and organ damage.


Due to the overwhelming number of metabolic disorders, diagnosis in a clinical setting can be difficult. The range of signs and symptoms that could possibly present is enormous. In general, infants and children who present with the following signs/symptoms may be investigated for a congenital metabolic disease, depending on their entire clinical picture and medical case history:


  • Failure to thrive
  • Growth failure
  • Developmental delay
  • Delayed or precocious puberty
  • Ambiguous genitalia
  • Seizures
  • Cardiac issues: cardiac failure, myocardial infarction and both high and low blood pressure
  • Skin: abnormal pigmentation, lack of pigmentation, excess body hair growth
  • Some childhood cancers
  • Hematological issues: low platelets, low red cell count, splenomegaly and lymphadenopathy
  • Diabetes
  • Musculoskeletal pain, weakness and cramping
  • Congenital malformations, especially involving facial features


In part 2 of this article: treatment and prevention, and where to seek help for metabolic disorders.




  1. Fernandes, John; Saudubray, Jean-Marie; Berghe, Georges van den (2013-03-14). Inborn Metabolic Diseases: Diagnosis and Treatment. Springer Science & Business Media. p. 4. ISBN9783662031476
  2. Jorde, et al. 2006. Carbohydrate metabolism. Medical Genetics. 3rd edition. Chapter 7. Biochemical genetics: Disorders of metabolism. pp139-142
  3. Ogier de Baulny H, Saudubray JM (2002). “Branched-chain organic acidurias”. Semin Neonatol. 7 (1): 65–74.
  4. Rosemeyer, Helmut (March 2004). “The Chemodiversity of Purine as a Constituent of Natural Products”. Chemistry & Biodiversity 1 (3): 361–401.
  5. Mark A. Sperling (25 April 2008). Pediatric Endocrinology E-Book. Elsevier Health Sciences. p. 35.
  6. Vernon, H. (2015). Inborn Errors of Metabolism. Advances in Diagnosis and Therapy. JAMA Pediatrics. 169(8): 778-782

Metabolic Disorders: Part II

Metabolic Disorders: Part Two

 Annalies Corse BMedSc, BHSc

Written for and originally published by the MINDD Foundation:

 In Part One of this article, the breadth of metabolic disorders was discussed. The important take away points from Part One included the following:

  • Metabolism is the sum total of all chemical reactions in the human body. Referring to metabolism by a simple reference to weight loss and weight gain is not entirely correct.
  • Metabolism consists of thousands of chemical reactions, where chemical entities are either synthesized for the body (anabolism), or broken down by the body (catabolism).
  • Metabolic reactions are accomplished by enzymes. Functionality of these enzymes is critical to your health, and is governed by your genes.

Treatment of Metabolic Disorders

As discussed in part one, the vast majority of metabolic disorders are genetic. They are heritable and exceptionally atypical. Most are autosomal recessive conditions, meaning that an affected child would need to inherit two copies of a faulty gene, one from each parent. Each parent would be a carrier of the faulty gene, and would likely be unaware of their genetic carrier status. Each carrier parent has one functional copy of the gene, and one faulty copy. The functional gene copy will correctly synthesize its enzyme product and compensate for the faulty gene + enzyme. No signs or symptoms of disease would be present for the parents.

The autosomal recessive inheritance pattern of metabolic disorders does prove problematic for prevention. Most parents are unaware they are carriers of specific genetic mutations, and the likelihood of having a child with a partner carrying the same mutation is exceedingly rare; too rare for pre-natal genetic screening of all babies to be necessary or feasible. In reality, the genetic mutation would have occurred many generations ago, and has been passed on through families, often undetected. Additionally, there are literally hundreds of metabolic disorders, and all require their own unique treatment approach; there is no blanket clinical protocol for treatment.

If a metabolic disorder is inherited, treatment options usually follow this clinical pattern:

  • If a specific food, drug or amino acid cannot be metabolized properly, its intake must be reduced or completely eliminated.
  • Enzymatic replacement of the faulty enzyme. This is only an option if enzymatic replacement (usually in the form of a medication) of the faulty enzyme actually exists.
  • Removal of toxic substances that accumulate via the faulty metabolic pathway.
  • Specific diets can remove specific macro or micronutrients that are not metabolized correctly.
  • Specific micronutrient supplements can support faulty metabolic pathways, depending on the specific metabolic disease in question.
  • Specific drug treatments to detoxify the blood of toxic metabolic by-product may be possible, depending on the disease in question.

As you can appreciate, altering diets to such a significant extent to reduce the possibility of other deficiencies and to prevent further illness requires the assistance of medical and nutritional experts.

 Prevention of Metabolic Disorders

Searching for information on the prevention of metabolic diseases is often fraught with frustration, as most sources will lead you to information regarding how to combat and prevent the metabolic syndrome (i.e., the cluster of conditions involving insulin resistance, obesity, dyslipidaemia and type II diabetes mellitus). Additionally, metabolic disorders are inherited, thus prevention is often deemed to be impossible, as they are inherited genetic disorders.

 Despite this, there are ways of eating and living life that are known to protect DNA and enhance the correct replication of DNA (thus preventing further mutations and even providing the healthiest genome possible to your future off spring). Whilst they may not prevent 100% of metabolic disorders in affected families, these strategies seek to safeguard the general health of all individuals and support healthy genes, from their replication through to gene expression. Additionally, well functioning organs and tissues will support treatments for metabolic disorders, and will have all affected individuals well placed to experience the best health the possibly can. This is the science of nutrigenomics; the “Genome-Food Interface”.

  • Cease all cigarette smoking and address excessive alcohol consumption. Both are known to have detrimental effects on our genes and how they function. Seek help to find ways to abstain from cigarettes permanently.
  • Many nutrients regulate gene expression, including folate, zinc, EPA and DHA to name just a few. Seek assistance from a health professional specializing in clinical nutrition and wholefood eating to formulate eating plans high in genome protecting nutrients.
  • Phytochemicals such as flavonoids, carotenoids, coumarins and phytosterols are also known to regulate gene expression. This is simple; eat lots of fruit and vegetables in abundance, everyday. This is especially important for both men and women in their reproductive years.
  • Healthy levels of folate, vitamin B12, niacin, vitamin E, retinol, and calcium are linked to decreased levels of DNA damage; riboflavin, pantothenic acid, and biotin are associated with an increase in DNA damage to the same extent observed with occupational exposure to genotoxic and carcinogenic chemicals. Do not self-prescribe supplements and gather information from integrative health professionals before considering supplementation.

 Where to seek assistance

 Many countries employ newborn screening programs to investigate the presence of metabolic disorders at birth. For example, screening for PKU forms part of the newborn screening panel. The diseases chosen for screening at birth have met certain clinical criteria for their inclusion in screening; the testing is reliable and non-invasive, and the treatment is straightforward and life saving. Many metabolic conditions do not manifest clinical signs at birth and are diagnosed in infancy or even later once evident signs and symptoms appear. In most cases, infants and children will be under the care of a specialist Paediatrician, and one who sub-specializes in specific metabolic conditions.

 Children and adults with metabolic disorders will require lifelong care and can often become ill very quickly. It is essential that they receive care from both their medical specialists and ideally an integrative doctor with their allied health teams. The MINDD Foundation is an excellent resource for locating doctors, nutritionists, naturopaths, pharmacists, dieticians and nurses experienced in the treatment of these rare and high-care diseases.

 “There is increasing evidence that genome instability, in the absence of overt exposure to genotoxicants, is itself a sensitive marker of nutritional deficiency”.

–Michael Fenech, CSIRO Genome Health and Nutrigenomics Laboratory



  1. Fernandes, John; Saudubray, Jean-Marie; Berghe, Georges van den (2013-03-14). Inborn Metabolic Diseases: Diagnosis and Treatment. Springer Science & Business Media. p. 4. ISBN9783662031476
  2. Jorde, et al. 2006. Carbohydrate metabolism. Medical Genetics. 3rd edition. Chapter 7. Biochemical genetics: Disorders of metabolism. pp139-142
  3. Meade, N. (2007). Nutrigenomics: The Genome-Food Interface. Environmental Health Perspectives. 115 (12): A582-A589.
  4. Ogier de Baulny H, Saudubray JM (2002). “Branched-chain organic acidurias”. Semin Neonatol. 7 (1): 65–74.
  5. Rosemeyer, Helmut (March 2004). “The Chemodiversity of Purine as a Constituent of Natural Products”. Chemistry & Biodiversity 1 (3): 361–401.
  6. Mark A. Sperling (25 April 2008). Pediatric Endocrinology E-Book. Elsevier Health Sciences. p. 35.
  7. Vernon, H. (2015). Inborn Errors of Metabolism. Advances in Diagnosis and Therapy. JAMA Pediatrics. 169(8): 778-782