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MALNUTRITION
LABORATORY FINDINGS
Decreased plasma albumin (<3.4 g/dl) and total
protein - correlates with the degree of fatty liver and oedema
Decreased total iron binding capacity (<240 mcg/dl)
- total iron binding capacity reflects transferrin concentration, which
is a sensitive and early indicator of protein deficiency
Decreased 24-hr urine creatinine - this should be
compared with the expected creatinine excretion based on the patient's
height and sex
Decreased total lymphocyte count (<1500/ul)
Decreased blood urea nitrogen (BUN), magnesium, and
urine urea nitrogen
Normocytic, normochromic anaemia - chronic disease
type
Laboratory findings of impaired intestinal absorption
and osteomalacia
DISORDERS OF AMINO-ACID TRANSPORT
AND METABOLISM top
Cystinuria is an inherited (genetic) disorder of the transport of
an amino acid (a building block of protein) called cystine resulting
in cystinuria (an excess of cystine in the urine) and the formation
of cystine stones.
Within the body, many molecules are able to pass across the
membranes that surround cells. These molecules can accomplish this
feat due to specific transport systems. These systems include special
receptors on the membrane of the cell and special carrier proteins.
The receptor recognizes the molecule and receives it on the cell
membrane. Then the molecule hitches a ride through the cell membrane
on the back of a carrier protein.
With such remarkable specificity, it is little wonder that
sometimes there are defects in transport systems. Several dozen
different diseases are now known to be due to transport defects.
Although cystine is not the only overly excreted amino acid in
cystinuria, it is the least soluble of all naturally occurring amino
acids. Cystine precipitates, or crystallizes out of urine and forms
stones (calculi) in the kidney, ureter, bladder, or anywhere in the
urinary tract.
The cystine stones (below) compared in size to a quarter (a U.S.
$0.25 coin) were obtained from the kidney of a young woman by
percutaneous nephrolithotripsy (PNL), a procedure for crushing and
removing the dense stubborn stones characteristic of cystinuria.
PHENYLKETONURIA (PKU) is an inherited error of metabolism caused by a deficiency in the enzyme phenylalanine hydroxylase. Loss of this enzyme results in mental retardation, organ damage, unusual posture and can, in cases of maternal PKU, severely compromise pregnancy.
Classical PKU is an autosomal recessive disorder, caused by mutations in both alleles of the gene for phenylalanine hydroxylase (PAH), found on chromosome 12. In the body, phenylalanine hydroxylase converts the amino acid phenylalanine to tyrosine, another amino acid. Mutations in both copies of the gene for PAH means that the enzyme is inactive or is less efficient, and the concentration of phenylalanine in the body can build up to toxic levels. In some cases, mutations in PAH will result in a phenotypically mild form of PKU called hyperphenylalanemia. Both diseases are the result of a variety of
mutations in the PAH locus; in those cases where a patient is heterozygous for two mutations of PAH (ie each copy of the gene has a different mutation), the milder mutation will predominate.
A form of PKU has been discovered in mice, and these model organisms are helping us to better understand the disease, and find treatments against it. With careful dietary supervision, children born with PKU can lead normal lives, and mothers who have the disease can produce healthy children. Extracted from NCBI page
LABORATORY FINDINGS
Increased urine phenylalanine and phenylpyruvic acid;
the latter might not appear until 2 weeks to 3 weeks of age
Increased plasma phenylalanine and decreased plasma
tyrosine occur when there is a normal phenylalanine intake. These
findings might not appear until after 4 days of age, after which time any
maternally transmitted enzymes will have been depleted.
Near-normal plasma phenylalanine occurs when dietary
phenylalanine intake is restricted to about 250 mg/day - 500 mg/day.
There is no increase in plasma tyrosine after a dietary
intake of increased phenylalanine.
Histidinemia
LABORATORY FINDINGS
Increased plasma histidine is the characteristic
laboratory finding.
Increased urine histidine, especially after meals
Homocystinuria
LABORATORY FINDINGS
Increased serum, urine, and cerebrospinal fluid (CSF)
methionine and homocystine
Marked decrease in blood glucose due to impaired
hepatic release of glucose
Increased lactic acid, marked
Decreased bicarbonate and pH (metabolic acidosis)
due to increased lactic acid
Marked increase in triglycerides and cholesterol
due to impaired lipid metabolism
Increased serum uric acid due to decreased urinary
excretion of uric acid
Mild anaemia
Decreased serum phosphorus
Evidence of impaired platelet function - prlonged
bleeding time, decreased platelet adhesion, and defective platelet aggregation
Liver biopsy shows increased glycogen and diminished
glucose-6-phosphatase.
GALACTOSEMIA top
Galactosemia is an elevation of blood galactose levels. It may be due to a deficiency of
any of the three enzymes of the galactose catabolic pathway:
galactose-1-phosphate
uridyltransferase (Gal-1-PUT), galactokinase, or UDP-galactose-4-epimerase. Clinically,
deficiency of galactose-1-phosphate uridyltransferase (Gal-1-PUT) has become synonymous with
classic galactosemia. This autosomal recessive disorder occurs with an incidence of
approximately 1:40-60,000 in the general population. The symptoms can be severe in infancy
and may lead to death or severe neurologic damage if not recognized and treated.
Galactose is a monosaccharide present in many polysaccharides. Clinically, the most
important source is the disaccharide lactose. Lactose is the predominant carbohydrate in
human and most other animal milk, including cow's milk. Many commercially available infant
formulas contain lactose. However, other formulas, such as some soy-based formulas, do not
contain lactose. This is critical information to assess in patients as ingestion of
galactose is prerequisite to the development of clinical symptoms.
Galactosemia, due to a complete lack of Gal-1-PUT activity, presents in the first weeks of
life. The most prominent clinical features are liver dysfunction manifest as jaundice and
hypoglycemia; neurologic findings of irritability and seizures; and gastrointestinal
findings of poor feeding, vomiting, and diarrhea. Other findings include cataracts and
renal Fanconi's syndrome. Escherichia coli sepsis has been described in many patients with
galactosemia. If the diagnosis of galactosemia is not made in the neonatal period, failure
to thrive, chronic vomiting, hepatic cirrhosis, and mental retardation may develop in
infants who survive. The diagnosis can be suspected clinically by the presence of the
above symptoms, but some affected infants may be asymptomatic at the time of screening.
Positive non-glucose urine reducing substances increases suspicion of the condition, but
not all affected newborns will have a positive urine test.
There are several clinical variants due to genetic mutations in Gal-1-PUT that alter, but
do not eliminate, enzyme activity. The most common of these are the Duarte and Los Angeles
variants. Patients with these variants are usually clinically asymptomatic; however the
reduced enzyme activity will be detected by newborn screening. Further testing is required.
Galactokinase deficiency
This is a rare defect manifest only by the development of cataracts, usually in the
neonatal period, but occasionally delayed until adulthood. The toxic symptoms of
Gal-1-PUT
deficiency are not present, however the urine may be positive for reducing substances.
Consideration of galactokinase deficiency should be given in any patient with an abnormal
total galactose result and a normal Gal-1-PUT on the newborn screen.
UDP-galactose-4-epimerase deficiency
This is a very rare cause of galactosemia that may be either symptomatic or asymptomatic.
Consideration should be given in any patient with an abnormal total galactose result and a
normal Gal-1-PUT on the newborn screen.
LABORATORY FINDINGS
Increased plasma galactose and galactose-1-phosphate
- result of impaired conversion of galactose to glucose
Galactosuria
Aminoaciduria and proteinuria reflect renal tubular
dysfunction.
Lack of galactose transferase in RBC
Hyperchloremic metabolic acidosis reflects the effect
of diarrhoea or renal tubular acidosis.
Impaired lactose tolerance test - minimal rise in
blood glucose after ingestion of lactose; diarrhoea occurs
Normal tolerance test of glucose and galactose -
normal rise in blood glucose when the two monosaccharides are ingested
separately; no diarrhoea occurs
Decreased stool pH due to increased lactic
acid
Increased stool lactose indicated by positive Clinitest
reaction of stool
Causes and Risks: Affected people have consistently high levels of low-density lipoprotein, which leads to premature atherosclerosis of the coronary arteries. Typically in affected men, acute myocardial infarctions ( heart attacks ) occur in their 40s to 50s, and 85% of men with this disorder have experienced a heart attack by age 60. The incidence of heart attacks in women with this disorder is also increased, but delayed 10 years later than in men.
Individuals from families with a strong history of early heart attacks should be evaluated with a lipid screen. Proper diet, exercise , and the use of newer drugs can bring lipids down to safer levels.
It is possible for a person to inherit two genes for this disorder. This magnifies the severity of the condition. Cholesterol values may exceed 600 mg/cc. Affected individuals develop waxy plaques (xanthomas) beneath the skin over their elbows, knees, buttocks. These are deposits of cholesterol in the skin. In addition they develop deposits in tendons and around the cornea of the eye. Atherosclerosis begins before puberty and heart attacks and death may occur before age 30. Little of therapeutic value is presently available for this condition.
The incidence of familial hypercholesterolemia is 7 out of 1000 people.
Prevention: In families with a history of familial hypercholesterolemia, genetic counseling may be of benefit, especially if both parents are affected. Prevention of early heart attacks requires recognition of existing elevated LDL levels, and a low-cholesterol, low-saturated fat , high-unsaturated fat diet in high-risk people may help to control LDL levels.
Symptoms:
a strong family history of early myocardial infarction
elevated and therapy-resistant levels of LDL in either or both parents
xanthomas (lesions caused by cholesterol deposits)
cholesterol deposits in the eyelids (xanthelasmas)
chest pain angina ) associated with coronary artery disease
evidence of obesity
Signs and Tests: A physical examination may reveal xanthomas and xanthelasmas.
Laboratory testing may show:
elevated triglycerides
protein electrophoresis
total plasma cholesterol that is greater than 300 mg/cc (adult)
total plasma cholesterol that is greater than 250 mg/cc (children)
serum LDL that is higher than 200
Xanthoma
Treatment: The goal of treatment is to reduce the risk of atherosclerotic heart disease and resulting myocardial infarction ( heart attack ).
Diet modification is the initial phase of treatment and is tried for several months before drug therapy is added. Diet modifications include reducing total fat intake to 30% of the total calories consumed. Saturated fat intake is reduced by decreasing the amounts of beef, pork, and lamb; substituting low-fat dairy products; and eliminating coconut and palm oil. Cholesterol intake is reduced by eliminating egg yolks and organ meats. Further reductions in the percentage of fat in the diet may be recommended after the initial trial period. Dietary counseling is often recommended to assist people with these adjustments to their eating habits.
Exercise, especially to induce weight loss , may also aid in lowering cholesterol levels .
Drug therapy may be initiated if diet, exercise, and weight reduction efforts have not reduced the cholesterol levels after an adequate trial period. Various cholesterol-reducing agents are available including:
bile acid sequestrant resins (cholestyramine and colestipol)
nicotinic acid
lovastatin
gemfibrozil
probucol
Prognosis: The outcome is likely to be poor in people with the homozygote type of familial hypercholesterolemia because it tends to be resistant to treatment.
The outcome of other types of familial hypercholesterolemia depends in part on the patient's compliance with treatment, but reduction in serum cholesterol levels can be achieved and may be significant in delaying a heart attack.
LABORATORY FINDINGS*
Plasma is usually clear after overnight refrigeration
- the increased LDLs are too small to diffract light and produce turbidity.
*These findings indicate Type IIa hyperlipoproteinemia.
ENDOGENOUS HYPERTRIGLYCERIDEMIA
Type IV Hyperlipoproteinemia (Endogenous Hypertriglyceridemia; Hyperprebetalipoproteinemia)
A common disorder, often with a familial distribution, characterized by variable elevations of plasma triglyceride contained predominantly in very low density lipoproteins and a possible predisposition to atherosclerosis.
Depending on the level of endogenous triglyceride used to define type IV hyperlipoproteinemia, the disorder is common in American middle-aged men.
Symptoms, Signs, and Diagnosis
This lipidemia is frequently associated with mildly abnormal glucose tolerance (insulin resistance) and obesity and may be exaggerated when dietary fat is restricted and carbohydrate is added reciprocally (with caloric intake kept constant). Plasma is turbid, and triglyceride levels are disproportionately elevated. TC may be normal or slightly increased (frequently secondary to stress, alcoholism, and dietary indiscretion) and may be associated with hyperuricemia. Low HDL levels result from triglyceride elevation and often normalize when triglyceride levels are reduced.
Prognosis and Treatment
The prognosis is uncertain. The disorder may be associated with premature CAD.
Weight reduction and limitation of alcohol consumption, when applicable, are the most effective treatments and will often reduce the triglycerides to normal levels. Maintenance of proper body weight and dietary restriction of carbohydrate and alcohol are important. Niacin 3 g/day po or gemfibrozil 0.6 to 1.2 g/day po in divided doses will further reduce the lipidemia in patients whose levels are not controlled by diet. Large doses of somatic fish oils (8 to 20 g/day) are frequently very effective in treating hypertriglyceridemia due to elevated VLDL levels.
LABORATORY FINDINGS
Mild Form*
Plasma appears turbid to opaque due to increased
VLDL, which diffract light but remain in stable dispersion; there
is no creamy layer after overnight refrigeration.
Electrophoresis - increased prebetalipoprotein (VLDL),
normal or slightly increased Beta-lipoprotein (LDL), normal chylomicrons.
The latter differentiates Type IV from Type V.
Severe Form**
Plasma is turbid to opaque due to VLDL, which diffract
light but remain in stable dispersion; after overnight refrigeration
the top layer is creamy owing to presence of chylomicrons.
Electrophoresis - increased Beta-lipoprotein
(LDL); increased "floating" Beta-lipoprotein, which is an
abnormal LDL that merges with the prebeta band - that is the characteristic
finding in the disorder; increased prebetalipoprotein (VLDL)
Synovial fluid - white blood cells (WBC) 5,000/ul - 50,000/ul
(avg 13,500); neutrophils 48% - 94% (avg 83%); increased complement.
Monosodium urate crystals are found free and also within WBC; they
are visualized when viewed microscopically under polarized light.
This finding establishes the diagnosis. Urate crystals are also seen
in biopsies of tophi.
Increased serum uric acid (more than 95% of patients)
Moderate leukocytosis during acute attacks
Increased urine uric-acid crystals and amorphous urates (10%-25% of patients)
Proteinuria - this precedes other evidence of renal disease
Decreased urine pH throughout the day due to inmpaired ammonia formation
Pseudogout (pronounced soo-doe-gowt) is a type of
arthritis that is caused by the build of calcium (pronounced cal-see-um) in
the body.
The calcium forms crystals that deposit in the
joints between bones. This causes swelling and pain in the area.
This is called inflammation.
The calcium deposits and inflammation can cause
parts of the joints to get weak and break down.
Cartilage is the tough elastic material that
covers and protects the ends of bones. With pseudogout bits of cartilage
may break off and cause more pain and swelling in the joint.
Over time the cartilage may wear away entirely,
and the bones rub together.
Pseudogout results from a build up of calcium
crystals (calcium pyrophosphate dihydrate) in a joint. The joint reacts to
the calcium crystals by becoming inflamed. The calcium deposits and chronic
inflammation can cause parts of the joint structure to weaken and break down.
Cartilage, the tough elastic material that cushions the ends of the bones, can
begin to crack and get holes in it. Bits of cartilage may break off into the
joint space and irritate soft tissues, such as muscles, and cause problems with
movement.
Much of the pain of pseudogout is a result of muscles
and the other tissues that help joints move (such as tendons and ligaments)
being forced to work in ways for which they were not designed, as a result of
damage to the cartilage. Cartilage itself does not have nerve cells, and
therefore cannot sense pain, but the muscles, tendons, ligaments and bones do.
After many years of cartilage erosion, bones may actually rub together. This
grinding of bone against bone adds further to the pain. Bones can also thicken
and form growths, called spurs or osteophytes, which rub together.
The word 'pseudogout' actually means 'fake' or
'imitation gout.' Like the disease gout, pseudogout can come on as sudden,
recurrent attacks of pain and swelling in a single joint. Gout is also caused by
the build-up of crystals within a joint. However, gout is caused by the
build-up of uric acid crystals, rather than the calcium crystals. Gout
usually attacks the big toe, while pseudogout most often attacks the
knee.
LABORATORY FINDINGS
Synovial fluid - coudy, yellow, low viscosity, fair
to good mucin clot; WBC average 20,000/ul; increased complement;
calcium pyrophosphate dihydrate crystals within WBC; these are best
visualised under polarised light
Leukocytosis in an acute attack
Increased sedimentation rate and C-reactive protein
reflect acute inflammation.
Increased serum iron and transferrin saturation,
marked
Decreased total iron binding capacity
Increased serum ferritin, marked - reflects increased
body iron stores; this gradually increases as the disease progresses
Increased serum glucose and decreased glucose tolerance
- indicates development of diabetes as a result of pancreatic scarring
from iron accumultion
Liver biopsy shows marked iron deposits in liver
cells and in Kupffer's RE cells.
WILSON'S DISEASE
Wilson's disease causes the body to retain copper. The liver of a person who has Wilson's disease does not release copper into bile as it should. Bile is a liquid produced by the liver that helps with digestion. As the intestines absorb copper from food, the copper builds up in the liver and injures liver tissue. Eventually, the damage causes the liver to release the copper directly into the bloodstream, which carries the copper throughout the body. The copper buildup leads to damage in the kidneys, brain, and eyes. If not treated, Wilson's disease can cause severe brain damage, liver failure, and death.
Wilson's disease is hereditary. Symptoms usually appear between the ages of 6 and 20 years, but can begin as late as age 40. The most characteristic sign is the Kayser-Fleischer ring--a rusty brown ring around the cornea of the eye that can be seen only through an eye exam. Other signs depend on whether the damage occurs in the liver, blood, central nervous system, urinary system, or musculoskeletal system. Many signs would be detected only by a doctor, like swelling of the liver and spleen; fluid buildup in the lining of the abdomen; anemia; low platelet and white blood cell count in the blood; high levels of amino acids, protein, uric acid, and carbohydrates in urine; and softening of the bones. Some symptoms are more obvious, like jaundice, which appears as yellowing of the eyes and skin; vomiting blood; speech and language problems; tremors in the arms and hands; and rigid muscles.
Wilson's disease is diagnosed through tests that measure the amount of copper in the blood, urine, and liver. An eye exam would detect the Kayser-Fleischer ring.
The disease is treated with lifelong use of D-penicillamine or trientine hydrochloride, drugs that help remove copper from tissue. Patients will also need to take vitamin B6 and follow a low-copper diet, which means avoiding mushrooms, nuts, chocolate, dried fruit, liver, and shellfish. Taking extra zinc may be helpful in blocking the intestines' absorption of copper.
Wilson's disease requires lifelong treatment. If the disorder is detected early and treated correctly, a person with Wilson's disease can enjoy completely normal health.
(Nordin BEC, Peacock M. Aaron J et al: Osteoporosis
and osteomalacia. Clin. Endocrinal Metab 9:177-205, 1980)
Usual Biochemical Abnormalities in Various
Types of Osteomalacia
FASTING PLASMA
VITAMIN-D-DEFICIENT
RENAL FAILURE
HYPOPHOSPHATAEMIA
Decreased calcium
X
X
Decreased phosphorus
X
X
Decreased calcium x phosphorous
X
X
Increased alkaline phosphatase
X
X
Increased parathyroid hormone
X
X
Decreased 25-hydroxyvitamin D3
X
X
(Modified from Nordin BEC, Peacock M. Aaron J
et al: Osteoporosis and osteomalacia. Clin. Endocrinol Metab
9:177-205, 1980)
LABORATORY FINDINGS
Laboratory Findings of Underlying Disorders
CYSTIC FIBROSIS
LABORATORY FINDINGS
Increased sweat chloride and sodium - this is a constant
and characteristic finding detectable at birth; the degree of electrolyte
elevation is related neither to the severity of the disease nor to the
extent of organ involvement.
Serum and urine electrolytes are normal.
Sputum culture - haemolytic Staphylococcus aureus
and
the mucoid form of Pseudomonas aeruginosa are commonly found.
Increased serum y-globulins, especially IgG
and IgA
Urine may be of normal colour when fresh and become
brown, red, or black on standing because of conversion of colourless PBG
to coloured uropoprphyrins.
Impaired glucose tolerance - similar to that in steroid-induced
diabetes
Hypercholesterolemia (250 mg/dl - 400 mg/dl)
Increased thyroxine (T4), free T4, or triiodothyronine
(T3) without clinical evidence of hyperthyroidism
Decreased serum sodium due to hypothalamic involvement,
producing inappropriate antidiuretic hormone (ADH) secretion, Renal and
GI sodium loss may also contribute to hyponatremia.
Variegate Porphyria
LABORATORY FINDINGS
Increased fecal protoporphyrin and coproporphyrin
- characteristic finding even during remission; higher levels occur
during acute attacks
Increased urinary ALA and PBG during acute attacks
Increased urinary coproporphyrin and uroporphyrin
Plasma may fluoresce owing to increased coproporphyrin
during acute photosensitivity attacks.
The description below is extracted from this web page: Newborn Screening Practitioner's Manual
