Disorders Of Amino Acid And Organic Acid Metabolism

Front 1

Amino Acid Disorders with
Chronic, progressive presentation

Back 1

Phenylketonuria (PKU)
Homocystinuria
Tyrosinemia I

Front 2

Organic Acid Disorders with
Acute Crises

Back 2

Proprionic Acidemia
Methylmalonic Acidemia (MMA)
Isovaleric Acidemia
Glutaric Acidemia I
Biotinidase Deficiency
Beta-ketothiolase Deficiency

Front 3

Clinical Symptoms of
Acute Metabolic Crisis

Back 3

Anorexia
Poor feeding
Vomiting/Dehydration
Hyperventilation
Lethargy/Coma
Seizures
Hypotonia
Stroke-like episodes
Reye-like syndrome (high ammonia, comatose)

Front 4

Clinical Symptoms of
Organic Acid Disorder, other

Back 4

Predisposition to infection
Bleeding tendency
Pancreatitis
Unusual odors
Ataxia
Movement disorder

Front 5

Incidence of Organic Acidemias
(from Newborn Screening)

Back 5

1/10,000 to 1/15,000

Front 6

Incidence of Urea Cycle Disorders

Back 6

checked and 2 refs. 1/30,000


1/8,000

Front 7

Incidence of Ornithine Trans-Carbamylase Deficiency

Back 7

1/80,000


1/15,000

Front 8

Urea Cycle Disorders by Type and Proportion

Back 8

CPS Def, 13%
OTC Def, 61% (x-linked)
ASAS Def, 14%
ASAL Def, 10%
Arginase Def, 1%

Front 9

Blood Gases in Organic Acidemias

Back 9

pH LOW
pCO2 LOW
HCO3 LOW

Front 10

Blood Gases in Urea Cycle Disorders

Back 10

pH HIGH
pCO2 LOW
HCO3 LOW

Front 11

Primary Metabolic Acidosis
Secondary Respiratory Alkylosis

Back 11

Organic Acidemia

Front 12

Primary Respiratory Alkylosis
Secondary Metabolic Acidosis

Back 12

Urea Cycle Disorder

Front 13

Neonate presents with:
tachypnea, elevated heart rate, low bp
hypotonia, high ammonia, metabolic acidosis

Back 13

Organic academia
(urea cycle disorders do not present with primary metabolic acidosis --when they first get sick)

Front 14

Metabolic ketoacidosis and hyperammonemia are suggestive of...

Back 14

Organic Acidemia

Front 15

Neutropenia

Back 15

White Cells are Low

Front 16

Thrombocytopenia

Back 16

Platelets are Low

Front 17

Glutaric Acidemia Type 1 Unusual Symptoms

Back 17

Macrocephaly
Fluid in frontal lobes and bilaterally in front of temporal lobes
(see this before acute crisis which usually follows infection and then permanently damages basal ganglia--severe motor impairment)

Front 18

Organic Acidemias
Chronic Symptoms

Back 18

Poor Feeding, FTT
Brain damage develops even without acute episodes
Hypotonic, movement disorder
Seizures
Developmental Delay

Front 19

Organic Acid Disorders with Recurrent Infections

Back 19

Proprionic Acidemia
Methylmalonic Acidemia
Biotinidase Deficiency

Front 20

Organic Acidemia with Eczemetous Rash and Alopcia (Hair Loss)

Back 20

Biotinidase Deficiency

Front 21

Organic Acidemia with Macrocephaly and Fluid in Frontal and Temporal Lobes

Back 21

Glutaric Acidemia Type 1

Front 22

Chronic Symptoms of Urea Cycle Disorders

Back 22

Protein Aversion, Chronic Nausea
Fatigue
Headaches, abdominal pain

Front 23

ASAL Deficiency Unusual Symptoms
(Arginosuccinic acid synthetase lyase deficiency)

Back 23

Hepatomegaly to cirrhosis
Trichorrexis nodosis(kinky, brittle hair)
(like Menke's syndrome)

Front 24

Unique Symptoms of
Arginase Deficiency

Back 24

Progressive Neurologic Disease
Spastic Diplegia
DD or MR

slightly elevated ammonia (not high enough for coma)

Front 25

Differential Diagnosis for SIDS

Back 25

Organic Acidemia
Urea Cycle Disorders
Fatty Acid Oxidation Defects
Disorders of Carnitine Transport
Disorders of Pyruvate Metabolism or Oxidative Phosphorylation
Carbohydrate Disorders (HFI, dis or glucogenesis)

Front 26

Precipitating Factors for Metabolic Crises

Back 26

Intercurrent Infections (fevers)
Inadequate Nutritional Intake
Excessive Protein Intake / Breakdown
Constipation/Altered Gut Motility (PPA, MMA)

Front 27

Phenylketonuria Symptoms
Amino Acid Disorder with Chronic Presentation

Back 27

Mental Retardation
Seizures
Psychiatric Disturbances
Hypopigmentation (low tyrosine, melanin precursor)
Skin Rashes (eczema)

Front 28

Homocystinuria Symptoms
Amino Acid Disorder with Chronic Presentation

Back 28

Tall, Marfan habitus
Thromboses (clotting issues)
arachnodactyly
pectus excavatum
Dislocated lenses
Myopia
Stiff Joints, scoliosis
Mental Retardation
Psychiatric Problems
Seizures
Elevated Methionine and Homocystine

Front 29

Marfans vs. Homocystinuria

Back 29

Hyperextensible joints in Marfan Syndrome, not stiff joints

Front 30

Tyrosinemia Type 1 Symptoms

Back 30

Bleeding, oozing
Large liver/spleen & Jaundice
Rickets
LIVER: failure, cirrhosis, ascites, coagulopathy, fasting intolerance.
KIDNEY: enlargement, dysfunction (Renal Fanconi Syndrom)
SKELETAL: Rickets
NEUROLOGIC crises (tachycardia, hypertension, pain..porphyria-like)

Front 31

Family History Questions when Metabolic Disease Considered.

Back 31

Consanguinity?
Crib Death/SIDS?
Reye Syndrome
Beware Atypical Dx (Atypical Schizophrenia, MS)
Pay careful attention to siblings, maternal lineage

Front 32

Keys to Making a Diagnosis

Back 32

1) Clinical Suspicion
2) Family History
3) Biochemical Features
4) Newborn Screening Really Helps!! (Tandem Mass Spectrometry)
5) Enzyme Assay (leukocytes, fibroblasts)
6) DNA Mutation Analysis

Front 33

Biological Features of Urea Cycle Disorders

Back 33

High Ammonia Levels
Primary Respiratory Alkylosis
Specific AA Patern
Urine Orotic Acid

Low BUN

Front 34

PKU Diet Restriction

Back 34

Phenylalanine

Front 35

Homocystinuria Diet Restriction

Back 35

Methionine

Front 36

Tyrosinemia Diet Restiction

Back 36

Tyrosine and Phenylalanine

Front 37

MSUD Diet Restricitons

Back 37

Leucine, Isoleucine and Valine

Front 38

Proprionic Acidemia and Methylmalonic Acidemia Diet Restrictions

Back 38

Methionine, Threonine, Valine and Isoleucine

Front 39

Isovaleric Acidemia Diet Restriction

Back 39

Leucine

Front 40

Urea Cycle Disorder Drug Therapy

Back 40

Vitamin B6 in Homocystinurea
Biotin Suppliment in Biotinidase Deficiency
Antibiotics in Proprionic Acidemia (gut bacteria)
Betaine in Homocystinuria

Front 41

Organ Transplants Indicated In

Back 41

Urea cycle disorders (liver)
Tyrosinemia type I (liver, +/- kidney)
Methylmalonic acidemia (liver, kidney)

Front 42

Clinical Symptoms of Galactosemia

Back 42

jaundice
bleeding/bruising problems
feeding problems
irritability/lethargy
sepsis (gram negative, newborn only)
cataracts

Front 43

Biochemical Signs of Galactosemia

Back 43

hyperbilirubinemia
abnormal liver function
coagulopathy
elevated amino acids in urine
hypoglycemia
renal fanconi syndrome

Front 44

Galactosemia--long term complications

Back 44

These occur EVEN if treated with galactose free diet
developmental delay
expressive language delay (verbal dyspraxia)
motor delays (ataxia, tremors)
premature ovarian failure
decreased bone density

Front 45

Galactosemia DIAGNOSIS

Back 45

prelim: newborn screening
confirm: clinitest positive, urine dipstick (glucose) negative

Front 46

Galactosemia Diagnosis

Back 46

Confirm by Galt Assay Classic <5% normal; Duarte 5-20% normal
Confirm by GALT isoelectric focusing
Confirm by molecular testing

Front 47

Classical Galactosemia Gene

Back 47

Q188R

Front 48

Duarte galactosemia gene

Back 48

N314D

Front 49

Galactosemia Therapy

Back 49

Stop breast and cow's milk/lactose free diet
Start soy feeding (fruits & veggies ok)
Consider septic risk
Treat liver disease and jaundice
Calcium supplementation
Monitor closely