PREVALENCE

The inborn errors of metabolism (IEM) constitute a diverse heterogeneous group of disorders with variable clinical manifestations presenting mainly in the pediatric population. Though individually rare, together they constitute a significant percentage of children seen in genetic and neurology clinics. Worldwide, the incidence of IEM is more than 1/1000. In India, the prevalence of IEM is one in 2497 newborns

WHAT ARE INBORN ERRORS OF METABOLISM (IEM)?

Many childhood conditions are caused by single gene mutations that encode specific proteins. These mutations can result in the alteration of primary protein structure or the amount of protein synthesized. The function of a protein, whether it is an enzyme, receptor, transport vehicle, membrane or structural element, may be relatively or seriously compromised. These disorders usually become clinically apparent in the newborn period or shortly thereafter.

COMMON CHARACTERISTICS OF GENETIC
DISORDERS OF METABOLISM

N

Lethargy

N

Poor Feeding

N

Convulsions

N

Vomiting

N

Weak Muscle Tone

N

Developmental Delays

DIAGNOSTIC TEST

More cases of inborn errors of metabolism are diagnosed by screening with tandem mass spectrometry (TMS) than are diagnosed clinically. It has a sensitivity close to 100% with a high positive predictive value (PPV) and the false positive rate is low (0.2-0.33% of babies screened needed further testing).
5 drops of blood are taken from the baby’s heel. Baby’s heel is pricked with a lancet and drops of blood are collected on special filter paper.
Infant must be 48 hours of age or older to obtain a satisfactory sample for screening. Ideal time is 4 days of age. Sample should be taken prior to administering antibiotics or transfusing blood or blood products.
TMS being the primary test should always be backed with a GCMS (Gas chromatography mass spectrometry) test to reconfirm the diagnosis. GC-MS is gold standard technology for confirming organic acid disorders in urine. The test is performed in a random urine from which organic compounds are extracted and analyzed by gas chromatography with mass spectrometric detector. Urine organic acid profile also provides a diagnostic clue to other inborn errors of metabolism including amino acid disorders, urea cycle disorders and fatty acid oxidation disorders.

AN APPROACH TO INBORN ERRORS OF METABOLISM

The management for IEM is a combination of 3 chief aspects – Nutritional Supplements, Dietary Modifications and Medical Care. Special diets play an important role in the treatment of affected children. Dietary changes should be tailored to each specific disorder. Awareness and attentiveness is crucial to a fruitful approach.

WHY ARE NUTRITIONAL SUPPLEMENTS IMPORTANT?

Growth outcomes in inborn errors of intermediary protein metabolism are not always ideal. Most patients with IEM consume insufficient natural protein to meet FAO/WHO/UNU recommendations. An extremely high Protein – Energy ratio correlates with optimal growth outcomes. 
Nutritional products for IEM treatment include two different forms of medical foods—one containing protein without the offending amino acid(s) and the other consisting of foods that have been modified to be low in protein. 
For example, medical foods for Phenylketonuria (PKU) provide the protein required for normal growth and development with no or negligible amounts of Phenylalanine. The majority, but not all, of these products also include other nutrients (such as fat, carbohydrate, vitamins, and minerals) needed to support normal nutritional status.
For many IEM, single amino acids and amino acid mixtures, vitamins, and other compounds are used to replace conditionally essential nutrients or enhance enzyme activity. For example, arginine must be supplemented in the diets of individuals with certain urea cycle disorders because their bodies produce insufficient amounts (except in cases of arginase deficiency)

PRISTINE SOLUTIONS

IEM Description Age Group Pristine Metanutrition Protein (%) Pristine Metanutrition Product Name
AMINOACIDOPATHIES
Phenylketonuria Phenylalanine Free Diet Infants & Toddlers 15 Metanutrition
PKU-1
Children & Adults 60 Metanutrition
PKU-2
Children & Adults 85 Metanutrition
PKU-3
Maple Syrup Urine Disorder Isoleucine, Leucine and Valine Free Diet Infants & Toddlers 15 Metanutrition MSUD-1
Children & Adults 48 Metanutrition
MSUD-2
Tyrosinemia Tyrosine and Phenylalanine Free Diet Infants & Toddlers 15 Metanutrition
TYROS-1
Children & Adults 48 Metanutrition
TYROS-2
Homocystinuria Methionine Free Diet Infants & Toddlers 15 Metanutrition
HCY-1
Children & Adults 48 Metanutrition
HCY-2
ORGANIC ACIDEMIAS
Isovaleric Acidemia, 3-Methylcrotonyl-CoA Carboxylase deficiency, 3-Methyl glutaconyl-CoA Hydratase Deficiency Leucine Free Diet Infants & Toddlers 20 Metanutrition
IVA-1
Children & Adults 48 Metanutrition
IVA-2
Methylmalonic Acidemia / Propionic Acidemia Isoleucine, Methionine, Threonine and Valine Free Diet Infants & Toddlers 15 Metanutrition
MMA/PA-1
Children & Adults 48 Metanutrition
MMA/PA-2
Glutaric Acidemia Type I Lysine and Tryptophan Free Diet Infants & Toddlers 15 Metanutrition
GA-1
Children & Adults 48 Metnautrition
GA-2
UREA CYCLE DISORDERS
Argininemia, Argininosuccinic Aciduria, Carbamoylphosphate Synthetase Deficiency, Citrullinemia Non-Essential Amino Acid Free Diet Infants & Toddlers 15 Metanutrition
UCD-1
Children & Adults 48 Metanutrition
UCD-2
LIPID DISORDERS
3-Hydroxy Long chain Acyl-CoA Dehydrogenase Deficiency LCHAD Deficiency Infants & Toddlers 15 Metanutrition
LCHAD
Defects in the Intraluminal Hydrolysis of Fat: Defective Mucosal Fat Absorption, Defective Lymphatic Transport of Fat Milk Protein Based Powder With Medium Chain Triglycerides (MCT) For Children And Adults Infants & Toddlers 15 Metanutrition
LD
CARBOHYDRATE METABOLISM DISORDERS
Galactosemia Galactose free formula Infants & Toddlers 15 Metanutrition
GLC
 Disorders of Carbohydrate Metabolism, Sucrase/Isomaltase Deficiency, Dissacharidase Deficiencies, Fructose Intolerance Protein Hydrolysate Formula Base Powder with Iron for Use with Added Carbohydrate. Infants & Toddlers 30 Metanutrition
CMD
Glucose Transport Defect Low Carbohydrate, Sucrose, Fructose, Sugar Free Formula Infants & Toddlers 15 Metanutrition
GTD
GENERAL FORMULATION
Amino Acid Metabolic Disorders Amino Acid And Protein Free Diet Powder Infants & Toddlers Nil Metanutrition
AAMD-1
Children & Adults Nil Metanutrition
AAMD-2
Non Ketotic Hyperglycinemia Amino Acid And Protein Free Diet Infants & Toddlers Nil Metanutrition
HLP
Low Protein Supplement Amino Acid Free Diet Infants & Toddlers 3 Metanutrition
LPS
Severe Allergy Due to Multiple Food Protein Intolerance Amino Acid Based Hypoallergenic Formula Infants & Toddlers 15 Metanutrition
MFPI
Severe Allergy Due to Intact Milk Protein and Soy Protein For Cow’s Milk Allergy Hypoallergenic Formula Infants & Toddlers 15 Metanutrition
SA MP/SP

PRISTINE SOLUTIONS: INDIVIDUAL INGREDIENTS

S.No. Individual Ingredient
1 Betaine
2 Carnitine
3 Sodium Benzoate
4 Isoleucine
5 Valine
6 Arginine
7 Citrulline
8 L-Methionine
9 Sialic Acid
10 N- Acetyl Mannosamine

REFERENCES

  • Nelson Textbook of Pediatrics, 20th Edition, 2015.
  • Alfadhel M, Al-Thihli K, Moubayed H, Eyaid W, Al-Jeraisy M. Drug treatment of inborn errors of metabolism: a systematic review. Archives of Disease in Childhood. 2013; 98:454–461.
  • Ramadevi AR, Naushad SM., Newborn screening in India. Indian Journal of Pediatrics. 2004; 71:157.
  • Kumta NB, Inborn errors of metabolism (IEM) — an Indian perspective. Indian Journal of Pediatrics. 2005 Apr; 72(4):325-32.
  • Camp, K. M., Lloyd-Puryear, M. A., & Huntington, K. L. (2012). Nutritional treatment for inborn errors of metabolism: indications, regulations, and availability of medical foods and dietary supplements using phenylketonuria as an example. Molecular genetics and metabolism, 107(1), 3-9.
  • Huidekoper, H. H., Wijburg, F. A., & Wanders, R. J. (2017). Inborn Errors of Metabolism. Mass Spectrometry and Stable Isotopes in Nutritional and PediatricResearch, 258-283.
  • Evans, M., Truby, H., & Boneh, A. (2017). The Relationship between Dietary Intake, Growth, and Body Composition in Inborn Errors of Intermediary Protein Metabolism. The Journal of Pediatrics.
  • Latheef SA. Bioinformation. 2010; 4:276-7.