Metabolic Screening – Urine:
Why Metabolic Screening – Urine Test?
CLINICAL INFORMATION
Metabolism is a life-sustaining chemical reaction catalyzed by bio-catalysts called enzymes. At the cellular level of organization in multicellular organisms, metabolisms are involved in maintaining the living state of the cells. Thus these metabolic chemical reactions are organized into metabolic pathways, where one substrate is sequentially converted into other metabolites through an organized series of systematic cascades of processes yielding the desired product required by the cells. Moreover, they are regulated by modulatory mechanisms (through intracellular signalling eg. feedback mechanisms etc). While few specialized tissue types (eg. liver) carry out their unique metabolisms, unlike other tissues. Hence metabolism is the sum total of metabolic (enzyme-mediated) chemical reactions (Metabolism = Anabolism + Catabolism) that occur within a living cell that provide vital energy (to carry out their activities such as movement, growth, development, reproduction etc), in each and every living organism. Anabolism is the synthesis of all metabolic compounds required by the cells. The food consumed when gets assimilated obtains nutrition which is the major source for anabolic processes. Catabolism is the breakdown of molecules to derive energy. While many of the important intermediary metabolites are recycled for anabolism. Inborn errors of metabolism are rare genetic inherited disorders (that occur due to mutations) in which the body fails to convert the primary metabolites (nutrition derived from the ingested digested food) into secondary or intermediary metabolites for their cellular requirements (activities) in tissues. The potential cause for such inborn errors of metabolism are due to hereditary enzyme deficiency and/or enzyme defects, where the conversion of one metabolite fails to convert into another (because of the absence of enzyme), therefore not only does the desired product is failed to obtain but also there are an unnecessary accumulation of certain metabolites in the system (found in the blood and/or urine) leading to congenital metabolic diseases. As a result due to defects in metabolism, there could be either too few or too many metabolites that can lead to detrimental impacts on normal growth and development. They are classified into various types such as disorders of carbohydrate metabolism, amino acid metabolism, urea cycle disorders, disorders of organic acid metabolism (organic acidurias eg alkaptonuria, 2-hydroxyglutaric acidurias etc), disorders of fatty acid metabolism, disorders of mitochondrial metabolism, disorders of porphyrin metabolism, disorders of purine and pyrimidine metabolism, disorders of steroid metabolism, disorders of peroxisomal function, lysosomal storage diseases etc. This test includes amino acids – 9 days test - this urine analysis plays a vital role in the diagnosis of the screening of certain in-born-errors of metabolism (especially protein) which is expelled in urine. Hence deficiencies or excess accumulation of these amino acids results in the manifestation of signs and symptoms of a particular amino acid disorder. The screening test is useful for evaluating patients with in-born-errors of metabolism (such as tyrosinemia, phenylketonuria, Maple syrup urine disease, homo-cystinuria, Alkaptonuriaetc), or amino acid transport defects (such as lysinuria protein intolerance and Hartnup disease) and renal tubular dysfunctions (as seen in conditions like Lowe syndrome and Dent disease etc), using random urine specimen as there can be elevations in urine amino acid levels known as aminoaciduria. Moreover, these test results will lead to clues in the evaluation of endocrine disorders, liver diseases, muscle diseases (hydroxyl-proline a major component of connective tissue collagen, synthesized from amino acid proline), neoplastic diseases, neurological disorders (amino acids such as glutamic acid and gamma aminobutyric acid – GABA and L-DOPA responsible in Parkinson’s disease), nutritional disturbances, renal failure, blood components (glycine is a biosynthetic precursor for porphyrins in heme biosynthesis – haemoglobin, a component of RBC), carnitine (in lipid transport for beta-oxidation of lipids) etc, since many amino acids and other intermediary substrates are the precursors for biosynthesis of essential proteins such as hormones. Thus these amino acids – 9 days test report is a quantitative random test performed in urine sample specimen exclusively to identify accumulation or deficiency of one or more amino acids in biological fluids (preferably in urine specimen). Undiagnosed and/or untreated cases may lead to complications and thus can result in mental retardation and death. These tests are indicated in clinical manifestations with the signs and symptoms including failure to thrive, neurologic symptoms, digestive problems, and dermatologic findings, physical and cognitive delays. Clinical manifestations include vomiting, diarrhoea, growth failure, developmental delay, abnormal pigmentation (i.e hypopigmentation or hyperpigmentation), seizures, encephalopathy, puberty issues (delayed or precocious puberty), hypogonadism, disorders of the immune system, hepato-splenomegaly, cancers, blood dyscrasias, urinary disorders, heart problems, liver dysfunction, respiratory issues, diseases of the thyroid, adrenal defects, kidney disorders, muscle and joint defects, diabetes etc. These metabolic defects can be detected by newborn screening tests. Urine metabolic screening tests aid in the detection of (aminoaciduria) certain metabolic disorders such as amino acid disorders etc. Moreover, porphyrias are classified under metabolic disorders. Porphine is the parent of porphyrin. Porphyrins are a group of heterocyclic macrocyclic organic compounds composed of 4 modified pyrrole subunits, interconnected at their alpha carbon atoms by methine bonds. Porphyrins are ubiquitous in biological systems. It is present as an active centre in haemoglobin, myoglobin, catalase, peroxidase, cytochrome P450 enzyme etc. The heme in haemoglobin contains protoporphyrin bound to an iron atom. AMINO-LEVULINIC ACID (ALA) or delta-aminolevulinic acid or 5--aminolevulinic acid is an amino acid synthesized by the liver. This is the first compound in porphyrin synthesis pathway that leads to heme biosynthesis. ALA test is to measure this substance excreted in the urine. Higher quantities of ALA are found in the urine in inherited acute porphyrias or due to inhibition of ALA dehydratase. Moreover 5ALA being a precursor of protoporphyrin-IX which is a photosensitizer is used as an add-on agent for photodynamic therapy in diagnosis (fluorescence imaging) and treatment of cancers (photosensitizer molecules) by computer simulations and can be able to penetrate tumor cell membranes. The principle behind it is that cancer cells lack or have reduced ferro-chelatase activity and hence it results in the accumulation of protoporphyrin-IX (its metabolic pathway precursor), a fluorescent substance that can be visualized. Porphyrias (means purple in Greek - The expression of the purple colour of urine during attack) refers to a group of disorders that result from a buildup of porphyrins in the body eg. porphyria cutanea tarda, acute intermittent porphyria, variegate porphyria, aminolevulinic acid dehydratase deficiency porphyria, hereditary coproporphyria, erythropoietic protoporphyria, hepato-erythropoietic porphyria etc. When these accumulated levels exceed, can affect skin and the nervous system known to cause disorder called as acute porphyrias. These porphyrias are inherited from either their parents by hereditary mutation of genes encoding heme and/or due to deficiency in (or dysfunctional) enzymes of the porphyrin pathway (in heme metabolism – cytosolic and/or mitochondrial enzymes), or due to poisoning such as mercury, arsenic etc. Clinical manifestation includes red brown urine, abdominal pain, chest pain, high BP, tachycardia (increased heart rate), fever, vomiting, constipation, blisters, itching when exposed to sunlight (photosensitivity), peripheral neuropathy, urinary retention, hyper-pigmentation etc. Untreated neglected cases can cause complications such as hyponatremia, paralysis (quadriplegia – paralysis of both hands and legs), seizures, coma, and psychiatric symptoms such as anxiety, confusion, hallucinations, psychosis etc. High-risk factors are smoking, alcohol, stress, fasting, hormonal changes, certain medications (sulfonamide, sulfonylureas, barbiturates, fluconazole, ketacanazole, rifampicin, isoniazid, nitrofurantoin, metronidazole, ergotamine, certain antiviral medications, carbamazepine, valproate, certain anticancer medications, antipsychotics, antidepressants, cocaine, methyldopa etc). Diagnosis for porphyria is typically made by blood, urine and/or stool sample specimen. To determine specific mutations, conformational tests are performed by genetic testing. Porphobilinogen (PBG) is one of the intermediate metabolites of the porphyrin biosynthesis pathway. Porphobilinogen is one of the several types of porphyrins found in the body. Urine estimation of porphobilinogen (PBG – a porphyrin precursor present in the urine of patients with porphyrias) is the screening test performed when the patient is suspected of acute porphyrias. Additional tests include spectrometry studies - mass spectrometry, gas chromatography-mass spectrometry, HPLC, Tandem mass spectrometry, ferric chloride test, ninhydrin test, Guthrie test, plasma acylcarnitine test, tissue biopsy, DNA testing, karyotyping, 24 hours PBG test, tests for uroporphyrin and coproporphyrin, enzyme tests (porphyrin pathway of heme metabolism) to detect enzyme deficiency, nerve conduction test for neuropathy, ultrasound of liver for hepatocellular carcinoma, LFT, blood sodium levels (for hyponatremia) etc. Other tests (such as enzyme assays, molecular analysis, etc) as a support and to rule out another differential diagnosis, PCR, ELISA, blotting techniques, liquid chromatography – Tandem Mass Spectroscopy (LC-MS/MS) etc.
General Instructions:
Sample Requirement: Specimen - Urine Sample. Test Preparation: None.
NOTE - Sample for specimen collections may vary based on the patient’s condition/cases according to the patient’s presenting complaints/signs or symptoms:
SPECIMEN REQUIREMENT (Special or Rare Cases) - As instructed and guided by Physician / Clinician / Pathologist / as per Laboratory’s requirements, according to procedures and protocols.
This Multi-Specialty Clinical Referral Laboratory RT DIAGNOSTICS provides precise and accurate tests with an extensive range of testing services to the medical centres to help in the diagnosis and identification of pathology in the test specimens for infectious diseases and also to evaluate the function of organ systems of the patient. It prevents further complications and helps to stabilize and restore health to near normalcy at the earliest without delay.
