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My DEMS Unit II > Inborn Errors of Metabolism > Flashcards

Inborn Errors of Metabolism Flashcards

1
Q

Definition of hypoglycemia

A

Whipple’s triad: classic symptoms–> BG resolution w/ glucose ingestion

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2
Q

ANS sx in hypoglycemia

A 
Sweating
Shaky, trembling
Tachycardia
Anxiety
Weakness
Hunger
Nausea/vomiting
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3
Q

Neuroglycopenic sx in hypoglycemia

A 
Irritable, restless
Headache
Confusion
Visual changes
Slurred speech/concentration
Behavior changes
Somnolence
Coma/seizures
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4
Q

hypoglycemia in kids: why ID and treat?

A

hypoglycemia can injure the developing brain and result in permanent neurodevelopmental problems

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5
Q

Hypoglycemia and timing:

A

Glucose 6 phosphatase deficiency
Milder Glycogen Storage Diseases in infants and children
Hyperinsulinism
Cortisol and GH deficiency in infants

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6
Q

> 6-8 hrs

A

Cortisol deficiency and fatty acid oxidation disorders in infants
Milder glycogen storage and gluconeogenic diseases
Cortisol and GH deficiency in children and adults

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7
Q

> 10-12

A

Fatty acid oxidation disorders in older children and adults

Mild disorders of GSD in adults

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8
Q

> 12-24 hrs

A

ketotic hypoglycemia

Fatty acid oxidation disorders in older children and adults

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9
Q

Most common cause of hypoglycemia in kids

A

-ketotic hypoglycemia
(don’t have enough aa or fat)
-not an inborn error

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10
Q

inborn errors of carb and fat metab

A
  • many present as hypoglycemia
  • May present with accumulation of abnormal amounts of substrate behind block: glycogen, galactose, fructose, lactate, triglycerides

Precipitating factors: fasting, illness, exercise, ingestion of dietary galactose or fructose.

Presence of ketones separates defects in fat oxidation from glucose disorders
(don’t burn fat? you don’t make ketones)

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11
Q

Names of inborn errors of carb metabolism

A

Glycogen storage diseases:
Glycogen synthase, branching enzyme
Glycogen phosphorylase, phosphorylase kinase

Gluconeogenic Defect: F1,6 bisphosphatase deficiency

Glucose 6 phosphatase deficiency

Hereditary Fructose Intolerance

Galactosemia

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12
Q

glucose 6 phoshphatase deficiency

A
  • presents as buildup of glycogen
  • liver can’t release glucose from glycogenolysis and gluconeogenesis
  • hepatomegaly
  • hypoglycemic
  • lactic acidosis
  • Hypertriglyceridemia and hypercholesterolemia
  • Hyperuricemia
  • Short stature, doll-like face
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13
Q

Glucose 6 phosphatase deficiency (GSD-I)

A 
Constant glucose supply!
Frequent feeding
Nasogastric drip feeding
Uncooked cornstarch: 
Slow release CHO, lasts 6 h, slow start

Any possible hypoglycemia needs prompt iv glucose treatment

Results:
Normalization of growth
Maintaining glucose > need for gluconeogenesis 
Decrease cholesterol and triglycerides
Still hepatomegaly but less pronounced
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14
Q

Glycogen synthase deficiency

A

Clinical presentation: hyperglycemia after a meal, followed by low blood sugar later, increased lactate, and severe ketotic hypoglycemia
No liver enlargement unlike other GSDs
Treatment: high protein diet to provide gluconeogenesis substrates and low glycemic index complex carbs to minimize post-prandial hyperglycemia and hyperlactacidemia

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15
Q

Branching enzyme deficiency

A

Abnormal glycogen: associated with tissue damage

Symptoms:
Progressive liver cirrhosis (transplant by age 4 – 6 YRS)

Hepatosplenomegaly, failure to thrive
Nonprogressive form: mild mutations

Cardiomyopathy

Muscle:
Neonatal severe hypotonia and muscle weakness
Childhood muscle weakness
Neuropathy

Diagnosis: pathology on muscle biopsy, enzyme assay in liver or fibroblasts, mutation analysis
Prognosis: mutation analysis can aid
Treatment: supportive

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16
Q

Disorders of glycogen breakdown

A

Glycogen Phosphorylase (GSD VI)

Glycogen Phosphorylase kinase (GSD IX)

Debranching Enzyme (GSD III)
17
Q

Debranching enzyme deficiency

A

Debranching enzyme: a-1,6-glucosidase
GSD-IIIA: deficiency in liver and muscle (85%)
GSD-IIIB: deficiency in liver only (15%)

Initial presentation:
Similar to GSD-I: hypoglycemia, hepatomegaly, growth retardation, mildly elevated cholesterol
lactate and uric acid normal
Elevation of liver enzymes, fasting ketosis

Late presentation:
Cardiomyopathy
Myopathy (3-4th decade) 
Polyneuropathy
Cirrhosis 
Abnormal glycogen causes tissue
    (Liver, heart, muscle) damage

Treatment:
Continuous glucose, raw cornstarch, to keep BG >70
High protein diet may help myopathy and growth failure

18
Q

Gluconeogenic enzyme deficiencies

A

Pyruvate Carboxylase and PEP Carboxykinase: rare- probably lethal

Fructose-1,6-bisPO4ase deficiency

19
Q

Fructose 1,6 bisophosphatase

A
  • will hypoglycemia, but slower onset
  • accumulate pyruvate
  • comes out as lactate

Hypoglycemia: late and mild
Metabolic acidosis: severe lactic acidosis
Normal lactate/pyruvate ratio
Often acidosis with Kussmaul breathing primary symptom
Ketones present and appropriate
Mildly elevated liver enzymes, no ammonia

TREATMENT:
Acute: give glucose -> will correct lactate
Give bicarbonate sparingly, acidosis corrects with glucose
Prevention: avoid long fasting, uncooked cornstarch at night
Prompt treatment of hypoglycemia

20
Q

Hereditary fructose intolerance

A

Due to deficiency in Aldolase B which splits Fructose 1 P into 3 carbon intermediates that can enter glycolysis.
Effect is accumulation of fructose 1P which has toxic effects on liver, kidney and brain
Symptoms occur with the introduction of fruits and other sources of fructose in the diet in the first year of life (not at birth or in the first few months)

Symptoms: nausea, vomiting, sweating, lethargy, hypoglycemia, hepatomegaly
Increased liver function tests, may progress to severe liver injury. Renal dysfunction may be present
Treatment is avoidance of fructose/sucrose/sorbitol in the diet.

21
Q

Galactosemia

A 
Signs and Symptoms*:
 Hypoglycemia
 Early Failure to Thrive (vomiting with milk)
 Hepatomegaly/Cirrhosis
 Cataracts/Visual Impairment
 Mental Retardation
Diagnosis: Non-glucose reducing substance in the urine while on lactose-containing diet: breast milk or infant formula
Treatment: Lactose-free diet

N.B.- Galactosemia is part of the Newborn Screening Program in most states

22
Q

Inborn errors of fat metabolism

A
  • won’t see large liver
  • see hypoglycemia but NO KETONES
  • decreased fat oxidation in liver deprives gluconeogenesis of a source of fuel
  • most tissues become obligate glucose users
Carnitine problems:
L-Carnitine- Primary or dietary
Carnitine Palmitoyl-Transferase (CPT)-I
Carnitine/Acylcarnitine Translocase
Carnitine Palmitoyl-Transferase (CPT)-II

Acyl CoA dehydrogenase deficiencies
MCAD, LCAD, etc

HMG-CoA Synthase/Lyase

23
Q

Decreased fatty acid oxidation and ketone formation features

A

Common clinical features include fasting hypoglycemia with low ketones, liver failure, hypotonia.
Lab features include hypoglycemia, low ketones, coagulopathy hyperammonemia, and elevated CK from exercise-induced rhabdomyolysis
Newborn screening has identified a combined incidence of 1:5000 for FAOD. Most are treatable with a good long term outcome.

24
Q

AcylCoA dehydrogenase deficiencies

A

Medium Chain [MCAD]- most common (1:9000)
Detected on the Newborn Screening Tests
Short Chain [SCAD]- rare
Long Chain [LCAD]- rare
All are Autosomal Recessively Inherited

Common Laboratory Features
Hypoglycemia
Abnormal urinary organic acids (omega-oxidation)
Increase in acylCoA derivatives in blood and urine
Decreased carnitine/Increased acylcarnitines- blood

25
Q

MCAD

A

Enzyme that catalyzes initial step in B-ox of C10-C6 straight chain acyl-CoAs
Clinical Features:
Vomiting, lethargy, hypotonia, +/- seizures
Hypoketotic hypoglycemia
Hepatomegaly, fatty liver
May resemble Reye syndrome (acute noninflammatory encephalopathy with hyperammonemia, liver dysfunction)
Rhabdomyolysis or cardiac symptoms (V fib and cardiac arrest) have been observed

Dx:
MS/MS-based acylcarnitine analysis of plasma with increased C8 and C8/ C10/carnitine ratio

Treatment:
Avoid fasting and provide a carb-rich diet
In those

26
Q

Hormonal dysregulation

A

Counterregulatory hormone Defects (insulin low):
Hypopituitarism
Growth Hormone Deficiency
ACTH or cortisol deficiency
Beta-blocker (results in lack of epinephrine)

Defects in Insulin Suppression (insulin high):
Congenital Hyperinsulinism
Infant of a diabetic mother
Iatrogenic
Insulinoma
27
Q

Clinical features of hypopituitarism

A 
Midline defects
Micropenis, undescended testes
Jaundice
nystagmus
Poor growth
28
Q

Primary adrenal insufficiency

A 
Clinical features:
Poor growth/weight gain
Decreased energy
Nausea, vomiting, abdominal pain
Hypotension
Hyperpigmentation
Salt craving
Associated autoimmune diseases
29
Q

Hyperinsulinism

A 
Neonatal:
Infants of Diabetic Mothers: “Transient”
Congenital hyperinsulinism “permanent”
 Childhood:
Islet Cell Adenoma
Insulin O.D., Type 1 DM, Child Abuse
Adolescents - as above and:
Oral Hypoglycemic Agent Ingestion
Factitious”- hypoglycemic symptoms only
30
Q

Features of hyperinsulinism in the newborn

A

Large for Gestational Age
Glucose Infusion Rate >10mg/kg/min to sustain normoglycemia
Non-ketotic (may see slight ketonuria)
Non-suppressed serum insulin
Rise in blood glucose >40mg/dL after glucagon (reflects increased storage of liver glycogen)

31
Q

Ketotic hypoglycemia

A

One of the most common causes of hypoglycemia in childhood
Diagnosis of exclusion
Lack of substrates for gluconeogenesis (small child, not much muscle, no body fat, not eating well)
Hypoglycemia after fasting 14-24 hours
Presents at 1-5 years old
Spontaneously remits at 8-9 years old

Low blood sugar high ketones

32
Q

Critical sample is key to eval hypoglycemia

A

CONFIRM BG

My DEMS Unit II (18 decks)

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