Metabolic Disease I

Objectives
Describe the epidemiology, clinical
features, and emergency management of:
1. Diabetes mellitus (hypoglycemia and DKA)
2. Water intoxication and diabetes insipidus
3. Metabolic diseases of the newborn and young
child
 Case Study 1:
Altered Mental Status
10-year-old boy presents with altered
mental status
2-week history of polyuria, weight loss
Complains of abdominal pain and weakness
Lethargic with mild tachypnea. Skin is pale.
 Initial Assessment (1 of 2)
PAT:
Abnormal appearance, abnormal
breathing, abnormal circulation
Vital signs:
HR 150, RR 45, BP 80/palp, O2 sat 100%
on room air
 Initial Assessment (2 of 2)
A: Good
B: Mild tachypnea with good air
exchange, no retractions
C: Skin pale and cool, skin turgor
poor, capillary refill time prolonged
D: Lethargic, arousable, cooperative
Bedside glucose check >500 mg%
 Detailed Physical Exam
Head: No evidence of trauma, eyes sunken, oral
mucosa dry, fruity breath odor
Neck: Supple
Lungs: Clear, mild tachypnea
Abdomen: Soft, mild, nonfocal tenderness, active
bowel sounds
Neuro: Lethargic, arousable, cooperative
Extremities: Cool to touch, delayed capillary refill
 Question
What is your general impression of this
patient?
 General Impression
Shock (decompensated)
Moderately severe dehydration and
hypovolemic shock (hypotension)
Suspected new onset diabetes and DKA

What are your initial management

priorities?
 Management Priorities
Place cardiorespiratory monitor.
Obtain vascular access.
Obtain blood for laboratory evaluation.
Begin fluid resuscitation with 20 mL/kg
NS.
 Case Progression
Glucose 600 mg%
Na 130, K 2.9, Cl 98, Bicarb 10
BUN 25, Creatinine 0.7
Venous blood gas for pCO2 28 mm Hg
Serum ketones: Positive
 Background:
Diabetic Ketoacidosis
DKA is the most important complication of
type 1 diabetes mellitus.
Insulin concentrations are low.
Hyperglycemia with lipolysis, ketone bodies,
dehydration, acidosis
Causes of DKA in children include:
intercurrent illness (31%), omission or
incorrect insulin administration (69%).
Clinical Features: Your First Clue
History of polyuria, polydipsia, weight
loss, nausea, and vomiting
Signs of dehydration
Breath with fruity odor
Abdominal pain
Tachypnea
Lethargy
 Diagnostic Studies
DKA defined as:
Hyperglycemia (glucose > 200 mg%)
Acidosis (pH < 7.25 or bicarbonate <17)
Ketosis (serum or urine)
Electrolytes, BUN
CBC not very helpful
 Differential Diagnosis: What
Else?
Gastroenteritis
Hyperglycemic hyperosmolar nonketotic
(HHNK) coma
Glucose >600 mg%, often 1,000 to 2,000 mg%
Profound dehydration (cerebral dehydration)
Profound lethargy, coma
Little or no ketosis
Occurs more frequently with Type II diabetes
High mortality risk
 Fluid Administration in DKA
Most DKA patients are 7% dehydrated.
Administer 20 mL/kg NS or LR over 30
to 60 min, repeat to reverse shock.
Other fluid deficits should be replaced
gradually.
If no evidence of hypovolemia, be less
aggressive with fluid management.
 Hyperglycemia
Glucose is often lowered significantly with
fluid resuscitation.
Check bedside glucose hourly. Gradual
decline by 100 per hour is preferable.
Add glucose to IV fluid once glucose is
< 250-300 mg/dL to avoid hypoglycemia.
Begin insulin infusion at 0.1 g/kg/hr.
 Metabolic Acidosis
Due to lipolysis (ketoacids) and
dehydration (lactic acidosis)
Insulin and fluids are sufficient
treatment.
Bicarbonate treatment is not
recommended and is associated with
cerebral edema.
 Electrolyte Imbalance
Factitious hyponatremia (hyperglycemia
effect).
Potassium level is falsely elevated. Most
patients have true potassium depletion.
Hypophosphatemia
Once urine output is established, replace K,
half as KCl and half as Kphos (total 30-40
mEq/L).
 Cerebral Edema
Assess mental status and neurological
exam hourly.
CT or MRI if cerebral edema is suspected.
Treat with hyperosmolar agents such as
mannitol, but this is controversial.
Glucocorticoid efficacy is unclear.
Aggressive hyperventilation is probably
detrimental.
 Case Progression/Outcome
His glucose levels and mental status
improves.
His vomiting resolves.
His parents are taught to measure his blood
glucose and administer subcutaneous
insulin.
 Case Study 2:
Lethargy and Vomiting
14-month-old girl presents with
lethargy and vomiting
Yesterday, she had onset of tactile
fever, loss of appetite, and 10
episodes of emesis.
She is sleepy, tachypneic and color
is pale.
 Initial Assessment (1 of 2)
PAT:
Abnormal appearance, normal breathing,
abnormal circulation
Vital signs:
HR 170, RR 40, BP 80/40, O2 sat 100%
on room air
 Initial Assessment (2 of 2)
A: Patent
B: Good air exchange,no retractions
C: Warm and pale, skin turgor slightly
diminished, capillary refill time
delayed, mucus membranes sticky
D: Lethargic, poorly responsive
E: No signs of trauma, no rash
 Question
Rapid beside glucose is 20 mg%.

What is your general impression of this

patient?
 General Impression
Shock (compensated) and
CNS/metabolic dysfunction
Vomiting, moderate dehydration
Hypoglycemia

What are your initial management

priorities?
 Management Priorities
Place patient on cardiorespiratory
monitor.
Obtain IV access.
Send blood for laboratory studies.
Administer 2 mL/kg D25W IVP.
Begin fluid resuscitation 20 mL/kg NS.
 Diagnostic Studies
Blood gas, electrolytes, glucose,
lactate, ammonia, UA (ketonuria), CBC
may provide the first clue to the
diagnosis.
If an inborn error of metabolism is
suspected, draw and freeze blood and
urine samples for special studies
before treatment is initiated.
 Case Progression (1 of 2)
Na 135, K 3.4, Cl 98, bicarbonate 20
Glucose: 20 mg/dL
Frozen clot tubes drawn and held in
lab for special studies
Urine ketones: Negative
Repeat bedside glucose after IV
glucose infusion: 95 mg%
 Case Progression (2 of 2)
Suspected fatty acid oxidation disorder
based on nonketotic hypoglycemia
(most hypoglycemia is ketotic)
Consult metabolic/genetic expert.
Expert to assist in ordering special
studies from previously drawn frozen
blood ordered.
Avoid catabolic state.
 Background (1 of 5)
Many biochemical disorders identified
Each disorder is rare, but collectively the
aggregate incidence is relatively high.
Nonspecific presentation
Specialized laboratory testing required
Routine lab tests are helpful: Glucose,
electrolytes, CBC, lactate, ammonia, urine
ketones, urine reducing substances
 Background (2 of 5)
Most often autosomal recessive
Family history of consanguinity, similar
conditions, stillbirths, early deaths,
neurologic conditions
In general, symptoms begin after an interval
of good health following normal pregnancy
and delivery. Interval may range from a few
hours, days, months, or even longer.
 Background (3 of 5)
The child may do well until subjected
to a catabolic stress (infection, fasting,
dehydration) or an excessive load of
protein or carbohydrate.
This may trigger sudden severe
symptoms.
Sudden infant death, coma, seizures,
lethargy, apnea
 Background (4 of 5)
Symptoms are often nonspecific:
Irritability and feeding difficulties
Vomiting, dehydration, failure to thrive
Developmental regression, weak cry
Symptoms can disappear only to recur
in days, weeks, or months.
EEG may suggest diffuse
encephalopathy.
 Background (5 of 5)
Other symptoms may be suggestive:
Hepatomegaly
Reye-like syndrome presentation
Brittle hair
An unusual odor: Rancid butter, maple
syrup, sweaty feet, cat-like
Ketosis accompanies many of these
conditions.
 Possible Complications
Fatty acid oxidation disorders may progress
to multi-organ failure (Reye-like syndrome).
Seizures, cardiomyopathy, liver failure, and
kidney failure may supervene.
Cerebral edema of unclear pathogenesis:
This complication may also potentially occur
if a high rate of relatively dilute dextrose
solution (e.g., D5W) is used.
 Diagnostic Studies (1 of 2)
Urea cycle defects: Severe
hyperammonemia
Organic acidemias: Severe metabolic
acidosis, hyperammonemia
Fatty acid oxidation disorders: Hypoketotic
hypoglycemia
 Diagnostic Studies (2 of 2)
Draw and freeze blood samples for special
studies immediately before treatment.
Diagnostic metabolites may disappear after
treatment.
Consider special studies in unexpected
deaths.
Newborn blood spots can also be used.
 Differential Diagnosis: What
Else?
Infection, toxins, trauma, congenital
structural brain abnormalities, or
cardiopulmonary dysfunction
Hypoxic-ischemic encephalopathy,
intraventricular hemorrhage, sepsis,
heart failure, gastrointestinal illness
E. coli sepsis frequently supervenes in
neonates with galactosemia.
 Management
Correct dehydration and hypoglycemia.
D10W with electrolytes at 1.5 times
maintenance is usually adequate to stop
catabolic spiral.
Intravenous carnitine (100 mg/kg) may be
beneficial in certain organic acidemias and
fatty acid oxidation disorders.
 Management:
Known Patients with Inborn Error
of Metabolism
Parents and physicians must be contacted
for information and advice.
If patient not maintaining adequate fluid and
caloric intake or doesnt seem his or her
usual self, start IV fluids with dextrose even
in the absence of hypoglycemia or
metabolic imbalance to prevent a metabolic
crisis.
 Case Study 3:
Vomiting and Diarrhea
3-year-old girl presents to the office with
vomiting and diarrhea for 24 hours
8 vomiting episodes, 7 diarrhea episodes
Oral hydration at home
Lethargic and weak
Has voided 3 times in the last 24 hours
Previously healthy
 Initial Assessment (1 of 2)
PAT:
Abnormal appearance, normal breathing,
normal circulation
Vital signs:
HR 95, RR 45, BP 95/65, O2 sat 100% on
room air
 Initial Assessment (2 of 2)
A: Patent
B: Good air exchange, no retractions
C: Warm and pink, skin turgor slightly
diminished, capillary refill time brisk
D: Lethargic, arousable, cooperative
E: No signs of trauma, no rash
 Question
What is your general impression of this
patient?
 General Impression
CNS/metabolic dysfunction
Lethargy and weakness but without signs
of shock or respiratory failure
What are your initial management
priorities?
Office management?
Refer to ED by car or by ambulance?
 Management Priorities
Check blood glucose; treat if < 50
mg/dL.
Consider trial of oral rehydration.
Obtain vascular access if low glucose
or patient unable to take oral fluids.
IV fluid 20 mL/kg NS or lactated Ringers
over 30 to 60 min, then reassess
Refer to ED.
 Case Progression
Bedside glucose check 40 mg%
Glucose infusion
More awake and alert
Recheck glucose 85 mg%
Oral feeding (carbohydrates)
 Background
Mild hypoglycemic episodes
(weakness, drowsiness) more
common than severe hypoglycemia
(e.g., with LOC or seizures)
Hypoglycemia in diabetes mellitus
Hypoglycemia in non-diabetics
 Hypoglycemia in DM (1 of 2)
Risk factors: Younger age, lower
hemoglobin A1C values,
underinsurance, and higher daily
insulin dose
Causes: Missed meals, exercise,
insulin dosing error; no cause
identified in 40% of episodes
 Hypoglycemia in DM (2 of 2)
Alterations in mental status (irritability,
combativeness, lethargy,
disorientation) may persist for
prolonged periods after serum glucose
concentrations have been restored.
Other neurological deficits (hemiplegia,
aphasia) may occur following such
episodes; may persist many hours.
Hypoglycemia in Non-DM (1 of 2)
Excessive insulin production
(insulinoma, hyperinsulinism)
Deficiency of counter-regulatory
hormones (growth hormone, cortisol)
Inborn metabolic errors that impair
gluconeogenesis, glycogenolysis, or
fatty acid oxidation
Hypoglycemia in Non-DM (2 of 2)
Some inborn errors are relatively benign
and are only identified during starvation
states such as in gastroenteritis.
Signs includes ketotic hypoglycemia
(evidence of failure to maintain glucose
level, resulting in lipolysis and ketosis)
Treatment is to provide glucose substrate.
Clinical Features: Your First Clue
(1 of 2)

Infants: Jitteriness, poor feeding, lethargy,

hypotonia, hypothermia, apneic episodes or
seizures
Older children: Headaches, visual changes,
mental status changes such as confusion,
lethargy, irritability or anxiety, and seizures
Severe hypoglycemia: Seizures, loss of
consciousness
Clinical Features: Your First Clue
(2 of 2)

Infant symptoms may also be subtle

and less obvious than those in older
children.
Hypoglycemia Adrenergic Symptoms:
Palpitations, tremulousness, sweating,
pallor
Hypoglycemia should be considered in
all pediatric resuscitation procedures.
 Diagnostic Studies
Bedside glucose check; definitely
hypoglycemia if <50 mg/dL
Draw venous sample for lab confirmation.
Draw and hold clot tube(s) simultaneously
(while the patient is still hypoglycemic) for
special endocrine studies.
Treat hypoglycemia while awaiting results.
 Differential Diagnosis: What
Else?
Toxic ingestion (oral hypoglycemic
agents, beta-blockers, ethanol)
Hypopituitarism
Adrenal insufficiency
Metabolic defects, ketotic
hypoglycemia
 Management:
Glucose Correction
IV glucose: 0.5 gm/kg
50 rule: D% x cc/kg = 50
D50W: 1 mL/kg
D25W: 2 mL/kg (toddler)
D10W: 5 mL/kg (infant)
D5W: 10 mL/kg
Glucagon 1 mg IM
 The Bottom Line
Maintain a high index of suspicion for
metabolic disorders in any infant or child
with altered mental status.
Simple laboratory tests such as glucose,
lactate, ketones, and ammonia levels can
give first clue to metabolic disorder.
Treat hypoglycemia quickly to avoid
complications.