CM LEC 7- URINARY SCREENING FOR METABOLIC DISORDERS

OVERFLOW DISORDERS

Results from disruption of a normal metabolic pathway that causes increased plasma concentrations of the nonmetabolized substances, depending on what metabolic pathway is affected

OVERFLOW DISORDERS

They either override the absorption ability of the renal tubules (too much of the specific substance to be reabsorbed, causing overflow) or not normally reabsorbed from the filtrate because they are only normally present in small amounts.

OVERFLOW DISORDERS

Most frequently encountered is associated with metabolic disturbances of fat, protein, and carbohydrates.

inborn error of metabolism

(OVERFLOW DISORDERS) caused by ___ ___ __ ______, which is the disruption of enzyme function caused by failure to inherit the gene to produce a particular enzyme.

complete breakdown

(OVERFLOW DISORDERS) This enzyme is specifically used for the ____ of a specific substance

RENAL DISORDERS

Caused by malfunctions in the tubular reabsorption mechanism

RENAL DISORDERS

Reappearance of abnormal metabolic substances in urine is caused by problems in tubular reabsorption.

NEWBORN SCREENING TEST

• Blood collected by heel puncture

• Collection is usually done by nurses, PGIs, and medical interns.

• Performed using tandem mass spectrophotometry (MS/MS)

  • The tandem mass spectrophotometry utilizes a card that contains blood samples from newborns

• Many of the urine tests discussed in this lecture were traditionally used to detect and monitor newborns for inborn errors of metabolism. However, currently, the screening of newborns has increased to include more sensitive detection methods, such as tandem mass spectrophotometry.

• Because many of these disorders cause the buildup of unmetabolized toxic substances, it is important that the defects be detected early in life. That’s why these samples are collected 24-48 hours after birth.

• Levels of these substances are elevated more rapidly in blood than in urine. That’s why testing blood is favored over urine.

heel puncture

(NEWBORN SCREENING TEST) Blood collected by ____

nurses, PGIs, and medical interns

(NEWBORN SCREENING TEST) Collection is usually done by ____, ____, and ____

tandem mass spectrophotometry (MS/MS)

(NEWBORN SCREENING TEST) Performed using _____________

inborn errors of metabolism

(NEWBORN SCREENING TEST) Many of the urine tests discussed in this lecture were traditionally used to detect and monitor newborns for _____. However, currently, the screening of newborns has increased to include more sensitive detection methods, such as tandem mass spectrophotometry.

24-48 hours after birth

(NEWBORN SCREENING TEST) Because many of these disorders cause the buildup of unmetabolized toxic substances, it is important that the defects be detected early in life. That’s why these samples are collected _____.

elevated more rapidly in blood than in urine

(NEWBORN SCREENING TEST) Levels of these substances are _______.

• phenylalanine-tyrosine disorders

• branched-chain amino acid disorders

AMINO ACID DISORDERS:

• phenylketonuria (PKU)

• tyrosyluria

• melanuria

• alkaptonuria

PHENYLALANINE-TYROSINE DISORDERS: 

• maple syrup urine disease

• organic acidemias

BRANCHED-CHAIN AMINO ACID DISORDERS:

BRANCHED-CHAIN AMINO ACIDS

_______ contain a methyl group that branches from the aliphatic carbon chain.

methyl group

Branched-chain amino acids contain a ____ that branches from the aliphatic carbon chain.

aliphatic carbon chain

Branched-chain amino acids contain a methyl group that branches from the _______.

• Disorders causing accumulation of one or more early amino acid degradation products (ex. MSUD)

• Disorders causing accumulation of organic acids produced further down in the amino acid metabolic pathway

2 Major groups of metabolic disorders:

• indicanuria

• 5-hydroxyindolacetic acid

TRYPTHOPHAN DISORDERS:

• cystinosis

• homocystinuria

CYSTEINE DISORDERS: