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49 Cards in this Set
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Amino Acid Disorders with
Chronic, progressive presentation |
Phenylketonuria (PKU)
Homocystinuria Tyrosinemia I |
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Organic Acid Disorders with
Acute Crises |
Proprionic Acidemia
Methylmalonic Acidemia (MMA) Isovaleric Acidemia Glutaric Acidemia I Biotinidase Deficiency Beta-ketothiolase Deficiency |
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Clinical Symptoms of
Acute Metabolic Crisis |
Anorexia
Poor feeding Vomiting/Dehydration Hyperventilation Lethargy/Coma Seizures Hypotonia Stroke-like episodes Reye-like syndrome (high ammonia, comatose) |
|
Clinical Symptoms of
Organic Acid Disorder, other |
Predisposition to infection
Bleeding tendency Pancreatitis Unusual odors Ataxia Movement disorder |
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Incidence of Organic Acidemias
(from Newborn Screening) |
1/10,000 to 1/15,000
|
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Incidence of Urea Cycle Disorders
|
checked and 2 refs. 1/30,000
1/8,000 |
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Incidence of Ornithine Trans-Carbamylase Deficiency
|
1/80,000
1/15,000 |
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Urea Cycle Disorders by Type and Proportion
|
CPS Def, 13%
OTC Def, 61% (x-linked) ASAS Def, 14% ASAL Def, 10% Arginase Def, 1% |
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Blood Gases in Organic Acidemias
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pH LOW
pCO2 LOW HCO3 LOW |
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Blood Gases in Urea Cycle Disorders
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pH HIGH
pCO2 LOW HCO3 LOW |
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Primary Metabolic Acidosis
Secondary Respiratory Alkylosis |
Organic Acidemia
|
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Primary Respiratory Alkylosis
Secondary Metabolic Acidosis |
Urea Cycle Disorder
|
|
Neonate presents with:
tachypnea, elevated heart rate, low bp hypotonia, high ammonia, metabolic acidosis |
Organic academia
(urea cycle disorders do not present with primary metabolic acidosis --when they first get sick) |
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Metabolic ketoacidosis and hyperammonemia are suggestive of...
|
Organic Acidemia
|
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Neutropenia
|
White Cells are Low
|
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Thrombocytopenia
|
Platelets are Low
|
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Glutaric Acidemia Type 1 Unusual Symptoms
|
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) |
|
Organic Acidemias
Chronic Symptoms |
Poor Feeding, FTT
Brain damage develops even without acute episodes Hypotonic, movement disorder Seizures Developmental Delay |
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Organic Acid Disorders with Recurrent Infections
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Proprionic Acidemia
Methylmalonic Acidemia Biotinidase Deficiency |
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Organic Acidemia with Eczemetous Rash and Alopcia (Hair Loss)
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Biotinidase Deficiency
|
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Organic Acidemia with Macrocephaly and Fluid in Frontal and Temporal Lobes
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Glutaric Acidemia Type 1
|
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Chronic Symptoms of Urea Cycle Disorders
|
Protein Aversion, Chronic Nausea
Fatigue Headaches, abdominal pain |
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ASAL Deficiency Unusual Symptoms
(Arginosuccinic acid synthetase lyase deficiency) |
Hepatomegaly to cirrhosis
Trichorrexis nodosis(kinky, brittle hair) (like Menke's syndrome) |
|
Unique Symptoms of
Arginase Deficiency |
Progressive Neurologic Disease
Spastic Diplegia DD or MR slightly elevated ammonia (not high enough for coma) |
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Differential Diagnosis for SIDS
|
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) |
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Precipitating Factors for Metabolic Crises
|
Intercurrent Infections (fevers)
Inadequate Nutritional Intake Excessive Protein Intake / Breakdown Constipation/Altered Gut Motility (PPA, MMA) |
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Phenylketonuria Symptoms
Amino Acid Disorder with Chronic Presentation |
Mental Retardation
Seizures Psychiatric Disturbances Hypopigmentation (low tyrosine, melanin precursor) Skin Rashes (eczema) |
|
Homocystinuria Symptoms
Amino Acid Disorder with Chronic Presentation |
Tall, Marfan habitus
Thromboses (clotting issues) arachnodactyly pectus excavatum Dislocated lenses Myopia Stiff Joints, scoliosis Mental Retardation Psychiatric Problems Seizures Elevated Methionine and Homocystine |
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Marfans vs. Homocystinuria
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Hyperextensible joints in Marfan Syndrome, not stiff joints
|
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Tyrosinemia Type 1 Symptoms
|
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) |
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Family History Questions when Metabolic Disease Considered.
|
Consanguinity?
Crib Death/SIDS? Reye Syndrome Beware Atypical Dx (Atypical Schizophrenia, MS) Pay careful attention to siblings, maternal lineage |
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Keys to Making a Diagnosis
|
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 |
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Biological Features of Urea Cycle Disorders
|
High Ammonia Levels
Primary Respiratory Alkylosis Specific AA Patern Urine Orotic Acid Low BUN |
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PKU Diet Restriction
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Phenylalanine
|
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Homocystinuria Diet Restriction
|
Methionine
|
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Tyrosinemia Diet Restiction
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Tyrosine and Phenylalanine
|
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MSUD Diet Restricitons
|
Leucine, Isoleucine and Valine
|
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Proprionic Acidemia and Methylmalonic Acidemia Diet Restrictions
|
Methionine, Threonine, Valine and Isoleucine
|
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Isovaleric Acidemia Diet Restriction
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Leucine
|
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Urea Cycle Disorder Drug Therapy
|
Vitamin B6 in Homocystinurea
Biotin Suppliment in Biotinidase Deficiency Antibiotics in Proprionic Acidemia (gut bacteria) Betaine in Homocystinuria |
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Organ Transplants Indicated In
|
Urea cycle disorders (liver)
Tyrosinemia type I (liver, +/- kidney) Methylmalonic acidemia (liver, kidney) |
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Clinical Symptoms of Galactosemia
|
jaundice
bleeding/bruising problems feeding problems irritability/lethargy sepsis (gram negative, newborn only) cataracts |
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Biochemical Signs of Galactosemia
|
hyperbilirubinemia
abnormal liver function coagulopathy elevated amino acids in urine hypoglycemia renal fanconi syndrome |
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Galactosemia--long term complications
|
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 |
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Galactosemia DIAGNOSIS
|
prelim: newborn screening
confirm: clinitest positive, urine dipstick (glucose) negative |
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Galactosemia Diagnosis
|
Confirm by Galt Assay Classic <5% normal; Duarte 5-20% normal
Confirm by GALT isoelectric focusing Confirm by molecular testing |
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Classical Galactosemia Gene
|
Q188R
|
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Duarte galactosemia gene
|
N314D
|
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Galactosemia Therapy
|
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 |