Term
| Cross Reactive Material (CRM) |
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Definition
Defined as a protein produced by a mutant gene that reacts antigenically with antibody against the normal protein. |
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Term
| Deficiency of enzyme activity |
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Definition
- CRM+
- the enzyme is present, but has deficient activity.
- Typically there is residual activityin these patients and they are clinically milder
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Term
| Deficiency of enzyme protein (CRM-) |
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Definition
- CRM-
- in these cases, deficiency of enzyme activity is due tono protein being produced
- there is no residual activity
- patients are clinically more severe
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Term
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Definition
- liver disease
- transient hyperammonemia of the newborn
- Reye syndrome
- poisonings
- inborn errors of metabolism
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Term
| What are the clinical and biochemical features of OTC deficiency |
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Definition
Clinical features: vomiting, lethargy, seizures, coma, mental retardation Biochemical features: orotic aciduria, increase in alanine
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Term
| Classical PKU: Clinical Features |
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Definition
- mental retardation
- "mousy odor"
- light pigmentation
- abnormal gait, stance and sitting posture
- eczema
- epilepsy
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Term
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Definition
- an autosomal recessive disorder involving deficiency of the liver enzyme phenylalanine hydroxylase
- incidence approx. 1/12,000; screened for birth in all US states and territories
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Term
| Classical PKU: Laboratory findings |
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Definition
- a plasma phenylalanine level above 20mg/dl
- phenylalanine/tyrosine ratio >3
- increased urinary metabolites of phenylalanine
- normal concentration of cofactor tetrahydrobiopterin
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Term
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Definition
Dietary restrictoin of phenylalanine; recommended for life. The goal of thereapy is to sustain growth while keeping circulating levels of phenylalanine below a specific threshold to minimize neurological damage
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Term
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Definition
- required cofactor for phenylalanine hydroxylase
- needed for tyrosine hydroxylase and tryptophan hydroxylase which are important for synthesis of dopamine and serotonin respectively
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Term
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Definition
- Classical PKU
- Persistent hyperphenylalaninemia: partial/residual activity
- Transient hyperphenylalaninemia: maturatoinal deficiency of PAH
- Cofactor defects: Tetrahydrobiopterin recycling or synthesis
- Maternal PKU
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Term
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Definition
a. phenylalanine is a teratogen b. untreated pregnant women with PKU have a higher incidence of miscarriage and infants born with mental retardation, congential heart disease, facial dysmorphism, and IUGR. c. Goal is to have Phe levels <6 mg% at least 3 months prior to conception |
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Term
| Nonketotic Hyperglycinemia |
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Definition
Deficient activity of glycine cleavage system due to defect, in most cases, of either the T or P protein Abnormal elevation of glycine in blood, urine and CSF; no other biochemical abnormalities. (The calculated CSF/plasma glycine concentration ratio: NKHG: >0.08, reference range: <0.04) Acute presentation: poor feeding, lethargy, intractable seizures, profound hypotonia, coma , and death. Cannot be treated by dietary restriction of glycine because we make glycine endogenously. |
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Term
| Variable clinical findings of Homocystinuria |
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Definition
- abnormal long bone formation, Marfan-like
- dislocated lenses; blindness
- increased risk for thromboembolytic events involving both large and small vessels, especially in the brain
- variable mental retardation (50% of patients)
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Term
| Heterogenous causes of homocystinuria |
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Definition
Cystathionine-b-synthase deficiency Defects of cytosolic cobalamin metabolism Remethylation defects 5,10-methylenetetrahydrofolate reductase deficiency 5-methyl-tetrahydrofolate-homocysteine-methyltransferase deficiency (methionine synthase) |
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Term
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Definition
- 1/150,000; Cystathionine-b-synthase deficiency
- Treatment: Betaine and pyridoxine (B6)-50% responders; low methionine diet
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Term
| Laboratory findings of classical homocystinuria |
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Definition
- Elevated plasma methionine and homocysteine
- Urine positive cyanide nitroprusside
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Term
| Acute treatments for hyperammonemia |
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Definition
- Conjugating agents such as Sodium Benzoate and Phenylacetate, are used to deplete the nitrogen pool via excretion of their glycine and glutamine conjugates respectively
- if those therapies fail to reduce the blood ammonia level within hours, hemodialysis or peritoneal dialysis must be implemented
- arginine supplementation will provide the arginine needed to keep the urea cycle supplied with enough ornithine
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Term
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Definition
- reacts with separated amines to form colored products (Ruhemann's purple)
- it is used laboratory diagnosis of aminoacidopathies
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