Congenital Disorders - ENBS Flashcards
Endocrine disorders
- Congenital hypothyroidism (CH)
- congenital adrenal hyperplasia (CAH)
Is a disorder resulting from thyroid dysgenesis (TD) that presents as an absent, ectopic or hypoplastic thyroid, which affects thyroid hormone production and commonly results in mental retardation
Congenital hypothyroidism
Is a group of disorders resulting from enzymatic defects in the biosynthesis of steroids such as 21-hydroxylase deficiency. Others are due to cholesterol demolish 11B-hydroxylase deficiency, and 17B-hydroxylase deficiency, and 3B-hydroxysteroid dehydrogenase
Congenital adrenal hyperplasia
Amino acid disorders
Homocystinuria
Methionine adenosine transferase (MAT) deficiency
Maple syrup urine disease
Phenylketonuria (PKU)
Tyrosinemia Type I and II
is caused by cystathionine B-synthase deficiency, an inborn error of the transsulfation pathway which causes an increase in levels of homocysteine and methionine in the blood.
Homocystinuria
is the abnormal elevation of plasma methionine that persists beyond infancy and is not caused by homocystinuria due to cystathionine B-synthase deficiency, tyrosinemia type I, or severe liver disease.
Methionine adenosine transferase deficiency
is due to a defect or deficiency of the branched-chain ketoacid dehydrogenase complex, in which elevated quantities of leucine, isoleucine, valine, and their corresponding oxoacids accumulate in body fluids
Maple syrup disease
is a disorder of aromatic amino acid metabolism in which phenylalanine cannot be converted to tyrosine due to a deficiency or absence of the enzyme phenylalanine hydroxylase.
Phenylketonuria
I is also known as hepatorenal tyrosinemia, tyrosinemia type 1, tyrosinosis, or hereditary tyrosinemia. The deficient enzyme is fumarylacetoacetase
Tyrosinemia type 1
is also known as oculocutaneous tyrosinemia or Richner- Hanhart syndrome. The deficient enzyme is tyrosine aminotransferase.
Tyrosinemia Type 2
Fatty acid oxidation disorders (FAOD)
- Carnitine palmitoyltransferase I deficiency (CPT1D)
- Carnitine palmitoyltransferase II deficiency (CPT2D)
- Carnitine uptake deficiency
- Glutaric acidemia type II (GA2)
- long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHADD)
- Medium chain-Acyl-CoA dehydrogenase deficiency (MCADD)
- Very long chain-Acyl-CoA dehydrogenase deficiency (VLCAD)
- Tri-functional protein deficiency
is a rare metabolic disorder characterized by the lack of CPT1
Carnitine palmitoyltransferase I deficiency (CPT1D)
is an enzyme of the outer mitochondrial membrane that converts long- chain fatty acyl molecules to their corresponding acylcamitines, which are then transported across the inner mitochondrial membrane for B-oxidation in the mitochondrial matrix.
Carnitine palmitoyltransferase
catalyzes the rate limiting step of long-chain fatty acid import into the mitochondria and is the main regulatory enzyme of the system.
Carnitine palmitoyltransferase
is the lack of carnitine palmitoyltransferase type II (CPT2). In this disorder, long-chain acylcarnitines are translocated across the inner mitochondrial membrane but are not efficiently converted to acyl-CoAs.
Carnitine palmitoyltransferase II deficiency (CPT2D)
is responsible for the last step of the carnine-dependent transport system.
carnitine palmitoyltransferase type II
It is due to an abnormality in the transport mechanism that facilitates carnitine’s entry into certain cells. In some instances it has been found that neonates who test positive for this condition do not actually have the condition but instead reflect the decreased levels of their mothers.
Carnitine uptake deficiency
Carnitine uptake deficiency is also known as?
Carnitine transporter deficiency
is a disorder of fatty acid, amino acid and
choline oxidation caused by defects in any one of two flavoproteins, electron transport flavoprotein (ETF) or ETF: ubiquinone oxidoreductase (ETFQO) which affects around 14 dehydrogenases.
Glutaric acidemia type 2
occurs when mutations in the HADHA gene are present in the newborn. _________ is a component of trifunctional protein302 and catalyzes the third step in the fatty acid oxidation spiral, converting long-chain 3-hydroxyacy-CoA esters into long-chain 3-keto-CoA species by using NAD as a cofactor
long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHADD)
is the most common defect of fatty acid oxidation and is associated with sudden infant death syndrome (SIDS).
Medium chain-acyl-CoA dehydrogenase deficiency (MCADD)
is generally a more severe condition than MCAD or SCAD deficiency and multiple
tissues are affected. ____________ catalyzes the dehydrogenation of C22-C12 straight-chain fatty acids, and because the long-chain fatty acids constitute a major proportion of the fatty acids, the disease prevents certain fats from being converted into energy
Very long chain-Acyl-CoA dehydrogenase deficiency (VLCAD)
occurs when markedly decreased activity of all three enzymatic components, LCHAD, long-chain 2,3 enoyl CoA hydratase and LKAT exist.
Tri-functional protein deficiency
Organic Acid Disorders
- 3-Methylcrotnyl CoA carboxylase deficiency
- Beta ketothiolase deficiency
- Glutaric acidemia type 1
- Isovaleric acidemia
- Methylmalonic acidemia
- Multiple carboxylase deficiency
- Propionic acidemia
is a disorder of leucine metabolism that was first described by Eldjarn et al. in 1970. In most instances, it has been found that neonates who test positive for this condition in ENBS do not actually have the condition but instead reflect the increased levels of the metabolites of their mothers.
3-Methylcrotnyl CoA carboxylase deficiency
is a defect of mitochondrial acetoactyl-CoA thiolase involving ketone body metabolism and isoleucine catabolism
Beta ketothiolase deficiency
was first described by Goodman and colleagues in 1975
Glutaric acidemia type 1
It is caused by a deficiency of glutayl-CoA dehydrogenase which catalyzes the oxidative decarboxylation of glutaryl-CoA, an intermediate in the degradation of the amino acids lysine and tryptophan. This cause an increase in glutaric, 3-hydroxyglutaric, glutaconic, and glutarylcarnitine.
Glutaric acidemia type 1
was the first organic acidemia to be described. It is caused by a deficiency of isovaleryl-CoA dehydrogenase, an enzyme located proximally in the catabolic pathway of the essential branched-chain amino acid leucine.
Isovaleric acidemia
is due to a defect in metholmalonyl CoA mutase or a defect in the enzyme’s vitamin B12 derived co-factor 5’-deoxyadenosylcobalamin. Among patients with thylmalonyl CoA mutase, two subgroups exist: Mut° patients have no enzyme activity while Mut’ patients have a spectrum of residual activity.
Methylmalonic acidemia
is caused by holocarboxylase synthetase enzyme, which is responsible for covalent binding of biotin with inactive apocarboxylases or by biotinidase deficiency
Multiple carboxylase deficiency
Urea Cycle Defects
Citrullinemia
Argininosuccinic aciduria
Hemoglabinopathies
Alpha thalassemia
Beta thalassemia
Hemoglobin C, D, E
Sickle Cell Disease
Other Diseases in ENBS
Galactosemia
Glucose-6-phosphate dehydrogenase deficiency
Cystic fibrosis
Biotinidase deficiency
is an inborn error of metabolism resulting from the deficiency of arginosuccinate synthetase, an enzyme present in all tissues but the level of which is highest in the liver where it helps facilitate the urea cycle.
Citrullinemia
The imbalance in the production of
globin chain results in hemolytic anemia or precipitation of the red cells in the
bone marrow or a process known as
Ineffective erythropoiesis
results from deletion of the a globin gene. The loss of four genes results in hydrops fetalis which is fatal in utero. The loss of three genes indicates HbH disease, which may manifest later in childhood as moderately severe anemia. Loss of two genes (trait) or one (silent carrier) may result in mild anemia and these two are clinically insignificant.
a (Alpha) thalassemia
may result in the total absence of P chain production (B°) or partial reduction of the chain (B+).
B (Beta) thalassemia
indicates that the newborn is a carrier of hemoglobin C, also known as hemoglobin C trait or Hb AC
Hemoglobin C
indicates that the newborn is a carrier of hemoglobin D, also known as hemoglobin D trait or Hb AD.
Hemoglobin D
occurs when the BE chain is synthesized at a reduced rate, leading to an imbalance in the globin chains.
Hemoglobin E
occurs in patients who have predominant HbS. The affected infants are usually normal at birth but develop anemia later when the HbS concentration increases and the HbF decreases.
Sickle cell diseases
is a rare genetic metabolic disorder that is inherited in an autosomal recessive manner. It is an inborn error of carbohydrate metabolism characterized by elevated levels of galactose and its metabolites due to enzyme deficiencies involved in its metabolism.
Galactosemia
is a genetic abnormality resulting in an inadequate or decreased production of G6PD,which renders RBCs susceptible to oxidative agents, leading to hemolytic anemia
Glucose-6-phosphate dehydrogenase deficiency
is a progressive genetic disease that causes persistent lung infections and limits the ability to breathe over time. People with CF inherited two copies of the defective CF gene; one copy from each parent. Both parents must have at least one copy of the defective gene for the disease to occur in their offspring
Cystic Fibrosis
is a form of multiple carboxylase deficiency in which the fundamental defect is an inability to cleave biocytin for biotin recycling
Biotinidase deficiency
Metabolite Tested - Congenital hypothyroidism
Thyroid stimulating hormone
Metabolite Tested - Congenital adrenal hyperplasia
17-hydroxy-progesterone (17 a-OHP)
Metabolite Tested - Homocystinuria
Methionine
Metabolite Tested - Hyperthioninemia/Methionine adenosine transferase deficiency
Methionine
Metabolite Tested - Maple syrup urine
Leucine
Metabolite Tested - Phenylketonuria
Phenylalanine
Metabolite Tested - Tyrosinemia 1,2,3
Succinylacetone (SA)
Tyrosine
Metabolite Tested - CPT1
Hexadecanoylcarnitine + CPT ratio
Metabolite Tested - CPT2
Hexadecanoylcarnitine + CPT ratio
Metabolite Tested - Carnitine uptake deficiency
Free cartinine
Metabolite Tested - Glutaric acidemia type 2
Butyrylcarnitine + Isovalerylcarnitine
Metabolite Tested - LCHAD
3-Hydroxyhexadecanoylcarnitine
Metabolite Tested - MCAD
Octanoylcarnitine
Metabolite Tested - VLCAD
Tetradecanoylcarnitine
Metabolite Tested - Tri-functional protein deficiency
Hydrocyhexadecanoylcarnitine
Metabolite Tested - 3-Methylcrotnyl CoA carboxylase deficiency
3-Hydroxyisovalerylcartinine
Metabolite Tested - Beta ketothiolase deficieny
Hydroxyisovalerylcarnitine
Metabolite Tested - Glutaric acidemia type 1
Glutarylcarnitine
Metabolite Tested - Isovaleric acidemia
Isovalerylcarnitine
Metabolite Tested - Methylmalonic acidemia
Propionylcarnitine
Metabolite Tested - Multiple carboxylase deficiency
3-Hydroxyisovalerycarnitine + Propionylcarnitine
Metabolite Tested - Propionic acidemia
Propionylcarnitine
Metabolite Tested - Citrullinemia
Citrulline
Metabolite Tested - Argininosuccinic acoduria
Citrulline
Metabolite Tested - Hemoglobinopathies
Hemoglobin
Metabolite Tested - Galactosemia
Total Galactose
Metabolite Tested - G6PD deficiency
G6PD enzyme activity
Metabolite Tested - Cystic Fibrosis
Immunoreactive trypsine
Metabolite Tested - Biotinidase deficiency
Biotinidase enzyme activity
