Biochemical Disorders – CBC 2002
1. Carbon Monoxide Poisoning
a. Symptoms:
A person exposed to carbon monoxide may exhibit flu-like symptoms:
1. Low levels (COHb levels of 10%)-shortness of breath on mild exertion, mild
headaches, nausea. Associated symptoms include sinus tachycardia, elevated
respiratory rates, and elevated pulse rates.
2. Higher levels(COHb levels of 30%)- symptoms become more severe including
dizziness, mental confusion, severe headaches, nausea, fainting on mild exertion.
3. High levels (COHb levels of 50% and above)- symptoms likely include
unconsciousness or even death.
b. Diagnostic Tests: Carboxyhemoglobin levels will be elevated, arterial blood
gas levels reveal metabolic acidosis as well as normal or slightly decreased Po2
and Pco2 (measured by pulse oximetry), serum creatine phosphokinase and lactate
dehydrogenase levels may also be elevated.
2. Stickler’s Syndrome
a. Possible Symptoms (Type I)
Marfanoid habitus, flat midface, sensorineural hearing loss, occasional conductive
hearing loss, myopia, retinal detachment, blindness, occasional cataracts,
glaucoma, membranous (type I) vitreous phenotype,
anteverted nares, depressed nasal bridge, cleft palate, Pierre-Robin sequence,
mitral valve prolapse, pectus excavatum, mild spondyloepiphyseal dysplasia,
platyspondyly with anterior wedging, scoliosis, kyphosis, flat/irregular femoral
epiphyses, arachnodactyly, arthropathy
b. Possible Symptoms (Type II – non-ocular)
Midface hypoplasia, sensorineural hearing loss, no ocular symptoms, anteverted
nares, Pierre-Robin sequence, cleft palate, epiphyseal dysplasia, mild
platyspondyly, joint pain, premature osteoarthritis, large epiphyses
c. Causes
Type I: Caused by mutations in type II collagen (COL2A1)
Type II: Caused by mutations in the collagen XI, alpha-2 gene (COL11A2)
d. Diagnostic Tests
Auditory tests, x-rays show signs of degenerative joint disease, molecular
techniques to amplify and sequence patient DNA.
3. Type I Glycogen Storage Disease
a. Symptoms
Initial symptoms of neonatal hypoglycemia occur shortly after birth, and episodes
do not respond to glucagon administration. Symptoms include the following:
Tremors Irritability Cyanosis Seizures Apnea Coma
Older infants may present with the following: Frequent lethargy, Difficult arousal
from overnight sleep, Tremors, Overwhelming hunger, Poor growth, Apparent
increase in abdominal girth, although extremities appear thin, A doll-like facial
appearance caused by adipose tissue deposition in the cheeks, Young children
with type Ia glycogenosis may experience nosebleeds. Young children with type
Ib glycogenosis may develop frequent otitides, gingivitis, and boils.
Symptoms of severe hypoglycemia at all ages are likely to follow any illness that
causes mild anorexia or fasting (eg, viral gastroenteritis).
In middle childhood, affected patients may manifest evidence of rickets and
anemia.
b. Diagnostic Tests
Initial laboratory workup should include blood glucose with electrolytes. If blood
glucose is low, electrolyte test results may permit calculation of an increased
anion gap, which suggests lactic acidemia.
Studies of liver function, plasma uric acid, and urinary creatinine clearance are
essential.
Perform a CBC and differential.
In type Ia glycogenosis, the WBC count generally is within reference ranges
because leukocyte function is unaffected by the defect.
In contrast, type Ib glycogenosis causes chronic granulocytopenia due to the
impaired function of the neutrophils, particularly in relation to gram-positive
organisms.
Perform a coagulation profile to include bleeding time tests.
Serum levels of liver enzymes ALT and LDH will be elevated.
4. Vitamin B12 Deficiency
a. Symptoms:
Unlike other water-soluble nutrients, vitamin B12 is stored in the liver, kidney,
and other body tissues. As a result, signs and symptoms of vitamin B12
deficiency may not show themselves until 5 to 6 years of poor dietary intake or
inadequate secretion of intrinsic factor. The classic deficiency symptom of
vitamin B12 deficiency is pernicious anemia. However, a deficiency of vitamin
B12 actually affects the brain and nervous system first.
A vitamin B12 deficiency results in impaired nerve function, which can cause
numbness, pins-and-needles sensations, or a burning feeling. It can also cause
impaired mental function that in the elderly mimics Alzheimer’s disease. Vitamin
B12 deficiency is thought to be quite common in the elderly and is a major cause
of depression in this age group.
In addition to anemia and nervous system symptoms, a vitamin B12 deficiency
can also result in a smooth, beefy red tongue and diarrhea. This occurs because
rapidly reproducing cells such as those that line the mouth and entire
gastrointestinal tract cannot replicate without vitamin B12. Folic acid
supplementation masks this deficiency symptom.
Manifested as Pernicious Anemia: weak muscles, numbness or tingling in hands
and feet, difficulty walking, nausea, decreased appetite, weight loss, irritability,
lack of energy or tiring easily (fatigue), diarrhea, smooth and tender tongue,
increased heart rate (tachycardia)
b. Diagnostic Tests
Serum B12 assays, bone marrow biopsies, Schilling Test, antibody (Parietal cell,
intrinsic factor, thyroglobulin, microsomal) tests, upper endoscopy. Hematocrit
levels in patients will also be lower than normal.
Measuring the level in the blood (serum cobalamin) or the level of methylmalonic
acid in the urine is the best method to determine vitamin B12 deficiency. In
addition, measuring the level of plasma homocysteine is emerging as a method to
determine the status of both vitamin B12 and folate. Another test, the Schilling
test, is used determine whether there is sufficient output of intrinsic factor. The
test involves oral administration of radioactive vitamin B12 and then measuring
the level excreted in the urine. Below-normal urinary excretion of the vitamin
suggests impaired absorption because of lack of intrinsic factor.
5. Type A Insulin Resistance
a. Symptoms
PCOS (Poly-cystic Ovarian Syndrome):
Amenorrhea (no menstrual period), infrequent menses, and/or oligomenorrhea
(irregular bleeding) — Cycles are often greater than six weeks in length, with
eight or fewer periods in a year. Irregular bleeding may include lengthy
bleeding episodes, scant or heavy periods, or frequent spotting.
Oligo or anovulation (infrequent or absent ovulation) — While women with
PCOS produce follicles — which are fluid-filled sacs on the ovary that contain
an egg — the follicles often do not mature and release as needed for ovulation.
It is these immature follicles that create the cysts.
Hyperandrogenism — Increased serum levels of male hormones. Specifically,
testosterone, androstenedione, and dehydroepiandrosterone sulfate (DHEAS).
Infertility — Infertility is the inability to get pregnant within six to 12 months
of unprotected intercourse, depending on age. With PCOS, infertility is usually
due to ovulatory dysfunction.
Cystic ovaries — Classic PCOS ovaries have a "string of pearls" or "pearl
necklace" appearance with many cysts (fluid-filled sacs). It is difficult to
diagnose PCOS without the presence of some cysts or ovarian enlargement, but
sometimes more subtle alterations may not have been recorded, or are not
recognized as abnormal, by the ultrasonographer.
Enlarged ovaries — Polycystic ovaries are usually 1.5 to 3 times larger than
normal.
Chronic pelvic pain — The exact cause of this pain isn't known, but it may be
due to enlarged ovaries leading to pelvic crowding. It is considered chronic
when it has been noted for greater than six months.
Obesity or weight gain — Commonly a woman with PCOS will have what is
called an apple figure where excess weight is concentrated heavily in the
abdomen, similar to the way men often gain weight, with comparatively
narrower arms and legs. The hip:waist ratio is smaller than on a pear-shaped
woman — meaning there is less difference between hip and waist
measurements. It should be noted that most, but not all, women with PCOS are
overweight.
Insulin resistance, hyperinsulinemia, and diabetes — Insulin resistance is a
condition where the body's use of insulin is inefficient. It is usually
accompanied by compensatory hyperinsulinemia — an over-production of
insulin. Both conditions often occur with normal glucose levels, and may be a
precursor to diabetes, in which glucose intolerance is further decreased and
blood glucose levels may also be elevated.
Dyslipidemia (lipid abnormalities) — Some women with PCOS have elevated
LDL and reduced HDL cholesterol levels, as well as high triglycerides.
Hypertension (high blood pressure) — Blood pressure readings over 140/90.
Hirsutism (excess hair) — Excess hair growth such as on the face, chest,
abdomen, thumbs, or toes.
Alopecia (male-pattern baldness or thinning hair) — The balding is more
common on the top of the head than at the temples.
Acne/Oily Skin/Seborrhea — Oil production is stimulated by overproduction
of androgens. Seborrhea is dandruff — flaking skin on the scalp caused by
excess oil.
Acanthosis nigricans (dark patches of skin, tan to dark brown/black) — Most
commonly on the back of the neck, but also but also in skin creases under arms,
breasts, and between thighs, occasionally on the hands, elbows and knees. The
darkened skin is usually velvety or rough to the touch.
Acrochordons (skin tags) — Tiny flaps (tags) of skin that usually cause no
symptoms unless irritated by rubbing.
b. Diagnostic Tests
In a pelvic examination, the health care provider may note an enlarged clitoris
(very rare finding) and enlarged ovaries.
LH (luteinizing hormone) to FSH (follicle stimulating hormone) ratio increased:
Normal LH (female): 5-20 IU/L (3x during midcycle peak)
Normal FSH (female): 5-30 IU/L (premenopause); 10-60 IU/L (midcycle);
0 – Low (pregnancy); > 30 IU/L (postmenopause)
Normal LH (male): 7-24 IU/L
Normal FSH (male): 4-25 IU/L
Vaginal ultrasound
Laparoscopy
Ovarian biopsy
Androgen (testosterone) levels elevated
Normal Values (male): 437-707 ng/dl
Normal Values (female): 24-47 ng/dl
Urine 17-ketosteroids (may be elevated)
Elevated LH
Estrogen level relatively high
FSH decreased
Serum HCG (pregnancy test) negative
This disease may also alter the results of the following tests:
Estriol - urine
Estriol - serum
6. Atherosclerosis
a. Symtpoms
Atherosclerosis shows no symptoms until a complication occurs.
b. Diagnostic Tests
Atherosclerosis may not be diagnosed until complications occur. Prior to
complications, atherosclerosis may be noted by the presence of a "bruit" (a
whooshing or blowing sound heard over the artery with a stethoscope). The
affected area may have a decreased pulse.
Tests that indicate atherosclerosis (or complications) include:
An abnormal difference between the blood pressure of the ankle and arm
(ankle/brachial index, or ABI)
A Doppler study of the affected area
Ultrasonic Duplex scanning
A CT scan of the affected area
Magnetic resonance arteriography (MRA)
An arteriography of the affected area
An intravascular ultrasound (IVUS) of the affected vessels
7. Hyperlipidemia
a. Symptoms
obesity may coexist
early onset of chest pain (angina)
family history of early heart attack or increased blood fats
Note: There may be no symptoms.
b. Diagnostic Tests
elevated serum LDL (> 160-189 mg/dl) or VLDL
elevated total cholesterol (> 200 mg/dl)
decreased or normal serum HDL cholesterol (< 40 (men) – 50 (women) mg/dl)
elevated triglycerides (> 200 mg/dl)
elevated apolipoprotein B100 test (> 40 – 125 mg/dl)
pedigree analysis may show parent or child with high blood fat
8. Alzheimer’s Disease
a. Symptoms
In the early stages, the symptoms may be very subtle. Symptoms may often
include:
Repeating statements frequently
Frequently misplacing items
Trouble finding names for familiar objects
Getting lost on familiar routes
Personality changes
Becoming passive and losing interest in things previously enjoyed
Some tasks that the person usually does well can become difficult at this stage.
Examples of these are balancing a checkbook, playing complex games (such as
bridge), and learning new and complex information or routines.
In a more advanced stage, the deficits are more obvious. Some of the symptoms
are:
A decrease in knowledge of recent events
Forgetting events in life history, essentially losing awareness of who you are
Problems choosing proper clothing
Hallucinations, arguments, striking out, and violent behavior
Delusions, depression, agitation
Some tasks that are likely to present difficulty for a person at this stage are:
preparing meals, driving, dressing, travel outside of familiar routes, and
managing finances.
In severe AD, a person can no longer survive without assistance. Most people in
this stage no longer understand language, they no longer recognize family
members, and they can no longer perform basic activities of daily living (such as
eating, dressing, and bathing).
b. Diagnostic Tests
The first step in diagnosing Alzheimer's disease is to establish that dementia is
present. Second, the type of dementia should be clarified. A health care provider
will take a history, do a physical exam (including a neurological exam), and do a
mental status examination.
Tests may be ordered to help determine if there is a treatable condition that could
cause dementia or contribute to the worsening of AD. These conditions include
thyroid disease, vitamin deficiency, brain tumor, drug and medication
intoxication, chronic infection, and severe depression.
AD usually has a characteristic pattern of symptoms and can be diagnosed by
history and physical exam by an experienced clinician. Tests that are often done
to evaluate or exclude other causes of dementia include Computed Tomography
(CT), magnetic resonance imaging (MRI), and blood tests.
In the early stages of dementia, brain image scans may be normal. In later stages,
an MRI may show a decrease in the size of the cortex of the brain or of the area
of the brain responsible for memory (the hippocampus). While the scans do not
confirm the diagnosis of AD, they do exclude other causes of dementia (such as
stroke and tumor).
9. Sickle-Cell Syndrome
a. Symptoms
joint pain and other bone pain
fatigue
breathlessness
rapid heart rate
delayed growth and puberty
susceptibility to infections
ulcers on the lower legs (in adolescents and adults)
jaundice
bone pain
attacks of abdominal pain
fever
Additional symptoms that may be associated with this disease:
bloody urine (hematuria)
excessive urination, excessive volume
thirst, excessive
unwanted painful erection (priapism; this occurs in 10-40% of men with the
disease)
chest pain
poor eyesight/blindness
b. Diagnostic Tests
Common signs include:
paleness
yellow eyes/skin
growth retardation
Tests commonly performed to diagnose and monitor patients with sickle cell anemia
include:
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Complete blood count (CBC)
RBC (varies with altitude):
male: 4.7 to 6.1 million cells/mcl;
female: 4.2 to 5.4 million cells/mcl
WBC: 4,500 to 10,000 cells/mcl
hematocrit (varies with altitude):
male: 40.7 to 50.3 %
female: 36.1 to 44.3 %
hemoglobin (varies with altitude):
male: 13.8 to 17.2 gm/dl
female: 12.1 to 15.1 gm/dl
MCV: 80 to 95 femtoliter
MCH: 27 to 31 pg/cell
MCHC: 32 to 36 gm/dl
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Hemoglobin electrophoresis
Adults (findings expressed as a percentage of total hemoglobin):
Hgb A1: 95% to 98%
Hgb A2: 2% to 3%
Hgb F: 0.8% to 2%
Hgb S: 0%
Hgb C: 0%
Children (findings expressed as a percentage of total hemoglobin):
Hgb F (newborn): 50% to 80%
Hgb F (6 months): 8%
Hgb F (over 6 months): 1% to 2%
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Sickle cell test
A negative test result is normal for the Sickledex, though it will be abnormal
also in patients with sickle trait.
In hemoglobin electrophoresis, no Hgb S should be present. Normal
hemoglobins in an adult are mostly Hgb A with small amounts of Hgb A2
and Hgb F.
Patients with sickle cell may have abnormal results on certain tests, as follows:
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peripheral smear displaying sickle cells
urinary casts or blood in the urine
Hemoglobin; serum decreased (normal 0.5-5.0 mg/dl)
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elevated bilirubin
(normal : direct bilirubin: 0 to 0.3 mg/dl; total bilirubin: 0.3 to 1.9 mg/dl)
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high white blood cell count
elevated serum potassium
elevated serum creatinine
blood oxygen saturation may be decreased
CT scan or MRI can display strokes in certain circumstances
10. Diabetes
a. Symptoms
-Too numerous to list, common symptoms include:
Type I (insulin-dependent):
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increased thirst
increased urination
weight loss despite increased appetite
nausea
vomiting
abdominal pain
fatigue
absence of menstruation
Type II (NIDDM)
Symptoms of type II diabetes include:
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increased thirst
increased urination
increased appetite
fatigue
blurred vision
frequent and/or slow-healing infections (including bladder, vaginal, skin)
weight loss despite increased appetite
erectile dysfunction in men
Note: There may be no symptoms or symptoms may develop slowly.
b. Diagnostic Tests
Type I Diabetes can be diagnosed when:
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urinalysis (shows glucose and ketone bodies in the urine)
fasting blood glucose is 126 mg/dL or higher
random glucose exceeds 200 mg/dL
elevated glycosylated hemoglobin (HbA1c) level (2.2 – 4.8%is normal)
insulin test (low or undetectable level of insulin) (5 –
normal)
C-peptide test (low or undetectable level of the protein C-peptide, a by-product of
insulin production)
Type II diabetes is diagnosed when:
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a fasting glucose level is above 126 milligrams per deciliter (mg/dl) on two
occasions.
a random glucose level is above 200 milligrams per deciliter with the classic
symptoms of increased thirst, urination, and fatigue.
a glucose level greater than 200, 2 hours after getting a standardized carbohydrate
beverage (Glucose Tolerance Test).
11. Cystic Fibrosis
a. Symptoms
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No bowel movements in first 24 to 48 hours of life
Stools, pale or clay colored, foul smelling, or stools that float
Skin may taste salty (infants)
Recurrent persistent respiratory infections, such as pneumonia or sinusitis
Coughing or wheezing
Weight loss
Diarrhea
Delayed growth
Easy fatigue
b. Diagnostic Tests
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Sweat chloride test (abnormal is > 90 mEq/L for Na+ and > 60 mEq/L for Cl-)
DNA testing
Fecal fat (normal is < 7g fat/24 hours)
Upper GI and small bowel series (under healthy conditions, the esophagus,
stomach, and small intestine will be normal in size and contour)
Measurement of pancreatic function
This disease may also alter the results of the following tests:
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Trypsin and chymotrypsin in stool (positive test is normal)
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Secretin stimulation test (test for pancreatic function)
Normal Values:
Volume: 107-223 ml/h;
Bicarbonate: 90-130 mEq/L;
Amylase: 174-1270 U/h
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Chest X-ray or CAT scan
Pulmonary function tests