PROTEIN METABOLISM CASES A 3 WEEK OLD INFANT WAS DIAGNOSED TO HAVE PHENYLKETONURIA 1) STATE THE ENZYME WHICH IS MOST

LIKELY TO BE DEFICIENT The enzyme deficient in phenylketonuria is phenylalanine hydroxylase 2) WHAT IS THE SCREENING TEST AVAILABLE The screening test for presence of phenylalanine in the urine is Guthries test. In this test infant blood is collected on a piece of filter paper and a small disk of the filter paper is punched out and placed on an agar gel plate containing Bacillus subtilis and beta 2 thienylalanine. The agar gel is able to support bacterial growth but the beta 2 thienylalanine inhibits bacterial growth. In the presence of extra phenylalanine leached out from the impregnated filter paper disk, the inhibition is overcome and the bacteria grow.

3) WHAT ARE THE TESTS FOR DIAGNOSIS OF PKU The positive result found in the screening test must be verified. The reference method for quantitative serum phenylalanine is high performance liquid chromatography (HPLC) however both fluorometric and enzymatic methods are available Another fast diagnostic procedure for neonatal PKU is microwave assisted silylation followed by gas chromatography mass spectrometry Prenatal diagnosis and detection of carrier status in families with PKU is done by DNA analysis 4) WHAT IS THE TREATMENT GIVEN TO THE PATIENT The goal of PKU treatment is to maintain the blood level of phenylalanine between 2 to 10 mg%. Some phenylalanine is needed for normal growth so a diet that has some phenylalanine but much lower amounts than normal is the recommended treatment. High protein food such as meat, fish, chicken, eggs, cheese and milk are avoided. Instead calculated amounts cereals, starches, fruits and vegetables along with a milk substitutes are usually recommended

A ONE YEAR OLD CHILD WITH DELAYED MILESTONES WAS BROUGHT TO THE HOSPITAL. HIS MOTHER GAVE HISTORY OF MOUSY ODOUR FROM HIS DIAPERS
1) 2) WHAT IS THE PROBABLE DIAGNOSIS The probable diagnosis is phenylketonuria WHAT IS THE BIOCHEMICAL BASIS OF DIAPER ODOUR In PKU there is accumulation of phenylalanine in the blood. Phenylalanine undergoes transamination to form phenyl puruvic acid which forms phenyl acetic acid. Phenyl acetic acid is conjugated with glutamine and is excreted as phenyl acetyl glutamine in the urine which gives mousy odour to the urine WHAT SHOULD BE THE MANAGEMENT OF THIS PATIENT The goal of PKU treatment is to maintain the blood level of phenylalanine between 2 to 10 mg%. Some phenylalanine is needed for normal growth so a diet that has some phenylalanine but much lower amounts than normal is the recommended treatment. High protein food such as meat, fish, chicken, eggs, cheese and milk are avoided. Instead calculated amounts cereals, starches, fruits and vegetables along with a milk substitutes are usually recommended DRAW THE REACTION CATALYZED BY THE DEFICIENT ENZYME The enzyme phenylalanine hydroxylase converts phenylalanine to tyrosine

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A 3 YEAR OLD BOY WAS ADMITTED TO THE HOSPITAL WITH SYMPTOMS OF PELLAGRA, ACCOMPANIED BY MENTAL RETARDATION AND EXCESSIVE EXCRETION OF NEUTRAL AMINO ACIDS. HE WAS DIAGNOSED AS HAVING HARTNUPS DISEASE
1) WHAT IS THE CAUSE OF HARTNUPS DISEASE Hartnups disease is caused due to impaired formation of transport proteins for tryptophan and neutral amino acids in the intestinal mucosa, renal tubular cells and the brain. There is defective intestinal and renal transport of tryptophan and other neutral amino acids WHY DOES IT SHOW MENTAL RETARDATION AND PELLAGRA SYMPTOMS Deposition of tryptophan in the brain causes mental retardation. Tryptophan forms niacin in the body , hence deficiency of tryptophan results in pellagra HOW WILL YOU TREAT PELLAGRA LIKE SYMPTOMS Pellagra like symptoms can be treated by increasing the intake of niacin in the diet CAN THE AMINOACIDURIA BE TREATED? HOW? Aminoaciduria is caused due to excessive excretion of a particular amino acid in the urine. This can be treated by decreasing the intake of that particular amino acid

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A 5 MONTH OLD FEMALE INFANT WAS ADMITTED TO THE HOSPITAL WITH A COMPLAINT OF VOMITING AND FAILURE TO GAIN WEIGHT. THE MOTHER ALSO REPERTED THAT THE CHILD WOULD OSCILLATE BETWEEN PERIODS OF IRRITABILITY AND LETHARGY. BIOCHEMICAL INVESTIGATIONS OF THE PATIENT INDICATED MARKEDLY INCREASED CONCENTRATION OF PLASMA AMMONIA
1) 2) NAME THE PROBABLE DISORDER The disorder is hyperammonemia WHAT IS THE CAUSE OF THE DISORDER The cause of the disorder is inherited deficiency of enzymes of the urea cycle NAME THE TRANSPORT FORM OF AMMONIA Ammonia is absorbed from the intestine into the portal blood. In normal conditions of health the liver promptly removes ammonia from the portal blood so that the blood leaving the liver is virtually ammonia free.the ammonia is converted to urea, forms glutamine or is used for the amination of alpha keto acid to alpha amino acid WHAT WILL BE THE NUTRITIONAL THERAPY FOR THIS PATIENT Nutritional therapy for this patient will be reducing the intake of proteins in the diet. High protein food such as meat, fish, chicken, eggs, cheese and milk are avoided. Instead calculated amounts cereals, starches, fruits and vegetables along with a milk substitutes are usually recommended

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A FULL TERM INFANT WAS OBSERVED TO HAVE LACK OF PIGMENTATION, BLUE EYES, WHITE HAIR AND CONFIRMED AS A CASE OF ALBINISM 1) NAME THE DEFICIENT PIGMENT The deficient pigment is melanin 2) NAME THE ENZYME RESPONSIBLE FOR THE DEFECT The enzyme responsible for the defect is tyrosinase 3) NAME THE AMINO ACID FROM WHICH THE PIGMENT IS SYNTHESIZED Melanin is synthesized from the amino acid tyrosine 4) WHAT ARE THE DIFFERENT TYPES OF ALBINISM Albinism can be classified as ocular albinism and oculo cutaneous albinism. Albinism can also be classified as tyrosinase negative albinism and tyrosinase positive albinism.

A 20 YEAR OLD MAN CAME TO THE EMERGENCY ROOM WITH SEVERE PAIN IN THE RIGHT SIDE AND BACK. SUBSEQUENT EXAMINATION AND EVALUATION INDICATED A KIDNEY STONE AND INCREASED EXCRETION OF CYSTINE, ARGININE AND LYSINE IN THE URINE AND DIAGNOSED AS A CASE OF CYSTINURIA
1) WHAT IS THE CAUSE OF CYSTINURIA Cystinuria is caused due to renal transport defect in the reabsorption of the amino acids cystine, lysine, arginine and ornithine. A single reabsorptive site is involved. WHY IS THERE FORMATION OF KIDNEY STONE Cystine is relatively insoluble amino acid, which may precipitate in renal tubules, ureters and bladder to form cystine calculi. HOW IS THE CONDITION TO BE TREATED The condition is treated by reducing the intake of proteins in the diet. High protein food such as meat, fish, chicken, eggs, cheese and milk are avoided. Instead calculated amounts cereals, starches, fruits and vegetables along with a milk substitutes are usually recommended NAME THE BIOSYNTHETIC PRECURSOR OF CYSTEINE The biosynthetic precursor of cysteine is methionine

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A 5 MONTH OLD FEMALE INFANT WAS HOSPITALISED. A DIAGNOSIS OF CLASSIC PHENYLKETONURIA WAS MADE
1) NAME THE DEFECTIVE ENZYME OF CLASSIC PHENYLKETONURIA The defective enzyme is phenylalanine hydroxylase which converts phenylalanine to tyrosine 2) WHAT ARE THE CHARACTERISITICS OF PHENYLKETONURIA Phenylketonuria is characterised by impaired melanin synthesis characterised by fair skin and fair hair. The child is mentally retarded and other features are seizures, psychoses and eczema. 3) NAME THE DIAGNOSTIC TEST FOR PHENYLKETONURIA The screening test for presence of phenylalanine in the urine is Guthries test. In this test infant blood is collected on a piece of filter paper and a small disk of the filter paper is punched out and placed on an agar gel plate containing Bacillus subtilis and beta 2 thienylalanine. The agar gel is able to support bacterial growth but the beta 2 thienylalanine inhibits bacterial growth. In the presence of extra phenylalanine leached out from the impregnated filter paper disk, the inhibition is overcome and the bacteria grow. The positive result found in the screening test must be verified. The reference method for quantitative serum phenylalanine is high performance liquid chromatography (HPLC) however both fluorometric and enzymatic methods are available Another fast diagnostic procedure for neonatal PKU is microwave assisted silylation followed by gas chromatography mass spectrometry Prenatal diagnosis and detection of carrier status in families with PKU is done by DNA analysis 4) GIVE THE TREATMENT OF PHENYLKETONURIA The goal of PKU treatment is to maintain the blood level of phenylalanine between 2 to 10 mg%. Some phenylalanine is needed for normal growth so a diet that has some phenylalanine but much lower amounts than normal is the recommended treatment. High protein food such as meat, fish, chicken, eggs, cheese and milk are avoided. Instead calculated amounts cereals, starches, fruits and vegetables along with a milk substitutes are usually recommended

A PATIENT WAS DIAGNOSED AS HAVING ALKAPTONURIA

1) OUTLINE THE BIOCHEMICAL PATHWAY AND POINT OUT THE METABOLIC DEFECT WHICH LEADS TO THIS CONDITION Alkaptonuria is caused due to deficiency of the enzyme homogentisate oxidase which converts homogentisic acid to maleyl acetoacetate STATE THE CHANGES IN URINE ON STANDING IN SUCH PATIENTS Urine in alkaptonuria patients turns dark on standing in air. Homogentisic acid is readily oxidized to black pigment alkapton. Urine when exposed to air slowly turns black from top to bottom. WHAT IS OCHRONOSIS Deposition of homogentisic acid derivatives in cartilages of ears and other exposed parts leads to generalized pigmentation of connective tissues and deposition in the joints leading to arthritis, a condition called ochronosis. The mechanism involves oxidation of homogentisate by polyphenol oxidase, forming benzoquinone acetate, which polymerizes and binds to connective tissue macromolecules. WHAT IS THE TREATMENT Treatment for alkaptonuria is high dose of vitamin C, which has been shown to decrease the buildup of brown pigment in the cartilage and may slow the development of arthritis.

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A 2 WEEK OLD FEMALE RESPONDED POSITIVELY TO A TEST FOR PHENYLKETONURIA. A DIAGNOSIS OF CLASSIC PHENYLKETONURIA WAS MADE.
1) NAME THE ENZYME DEFECT IN PHENYLKEONURIA The enzyme deficient in phenylketonuria is phenylalanine hydroxylase WHAT ARE THE PHYSIOLOGICAL CONSEQUENCES OF PHENYLKETONURIA AND WHY SHOULD IT BE DETECTED AS EARLY AS POSSIBLE Phenylketonuria is characterised by impaired melanin synthesis characterised by fair skin and fair hair. The child is mentally retarded and other features are seizures, psychoses and eczema. The disease should be detected as early as possible so that the treatment can be started and the consequences prevented. WHAT IS THE TREATMENT OF PHENYLKETONURIA The goal of PKU treatment is to maintain the blood level of phenylalanine between 2 to 10 mg%. Some phenylalanine is needed for normal growth so a diet that has some phenylalanine but much lower amounts than normal is the recommended treatment. High protein food such as meat, fish, chicken, eggs, cheese and milk are avoided. Instead calculated amounts cereals, starches, fruits and vegetables along with a milk substitutes are usually recommended GIVE THE FUNCTIONS OF TYROSINE The functions of tyrosine are synthesis of thyroid hormones, catecholamines, tyrosine sulphate, melanin and tyramine

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A 14 YEAR OLD BOY WAS ADMITTED TO THE HOSPITAL BECAUSE OF SUDDEN, SEVERE PAIN IN THE LEFT FLANK. URINARY ANALYSIS REVEALED THE PRESENCE OF HEXAGONAL CRYSTALS IN THE URINARY SEDIMENT. A 24 HOUR URINE COLLECTION INDICATED THAT THE PATIENT WAS EXCRETING A LARGE AMOUNT OF CYSTINE.
1) HOW IS CYSTINE SYNTHESIED IN THE BODY Cystine is synthesized in the body from cysteine by the action of the enzyme cysteine reductase WHAT IS THE CAUSE OF CYSTINURIA Cystinuria is caused due to renal transport defect in the reabsorption of the amino acids cystine, lysine, arginine and ornithine. A single reabsorptive site is involved WHAT IS THE RELATIONSHIP BETWEEN CYSTINE AND CYSTEINE Cysteine and cystine are both non essential amino acids. Cysteine is synthesized in the body from methionine. Cysteine can be converted to cystine by the enzyme cysteine reductase and this is a reversible reactions. Cysteine and cystine are interconvertible GIVE FUNCTIONS OF CYSTEINE Cysteine is required for the formation of cystine, pyruvate,glutathione, taurine, mercaptoethanolamine. Cysteine is a glucogenic amino acid. It is a prominent amino acid of hair and nails. It is a constituent of the hormones insulin and vasopressin. Cysteine also takes part in detoxication reactions.

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