hypochromic microcytic anaemias and thalassemia
Intensive Care Nursery House Staff Manual
Inborn Errors of Metabolism
INTRODUCTION and PATHOPHYSIOLOGY: Inborn Errors of Metabolism (IEM) comprise a group of disorders in which a single gene defect causes a clinically significant block in a metabolic pathway resulting either in accumulation of substrate behind the block or deficiency of the product. All IEMs are all genetically transmitted typically in an autosomal recessive or X-linked recessive fashion. The major categories are:
Organic acidemias (e.g., methylmalonic or propionic acidemia, multiple carboxylase deficiency) are caused by abnormal metabolism of proteins, fats or carbohydrates and are characterized by marked metabolic acidosis with ketosis, often with elevated lactate and mild to moderate hyperammonemia. Common signs include vomiting, signs of encephalopathy, neutropenia and thrombocytopenia.
Fatty acid oxidation defects (e.g., short, medium, and long- chain acyl-CoA dehydrogenase deficiencies) also known as Beta-oxidation defects, are a distinct type of organic acid disorder, characterized by hypoketotic hypoglycemia, hyperammonemia, and cardiomyopathy, and may present clinically with Reye’s syndrome. Medium-chain acyl-CoA dehydrogenase deficiency (MCAD) is among the most common of all IEMs and may account for 5% of SIDS cases.
Primary Lactic Acidoses (e.g., pyruvate dehydrogenase, pyruvate carboxylase and cytochrome oxidase deficiencies) present with severe lactic acidosis.
Aminoacidopathies (e.g., phenylketonuria, hereditary tyrosinemia, nonketotic hyperglycinemia, maple syrup urine disease [MSUD] and homocystinuria) may have similar presentation to the organic acidemias, but are a very heterogeneous group of disorders. Hereditary tyrosinemia can present in the neonate with a bleeding diathesis due to liver disease, or later in infancy with a renal Fanconi syndrome. The severe form of nonketotic hyperglycinemia presents as unremitting seizures with hypotonia and
Inborn Errors of Metabolism
INTRODUCTION and PATHOPHYSIOLOGY: Inborn Errors of Metabolism (IEM) comprise a group of disorders in which a single gene defect causes a clinically significant block in a metabolic pathway resulting either in accumulation of substrate behind the block or deficiency of the product. All IEMs are all genetically transmitted typically in an autosomal recessive or X-linked recessive fashion. The major categories are:
Organic acidemias (e.g., methylmalonic or propionic acidemia, multiple carboxylase deficiency) are caused by abnormal metabolism of proteins, fats or carbohydrates and are characterized by marked metabolic acidosis with ketosis, often with elevated lactate and mild to moderate hyperammonemia. Common signs include vomiting, signs of encephalopathy, neutropenia and thrombocytopenia.
Fatty acid oxidation defects (e.g., short, medium, and long- chain acyl-CoA dehydrogenase deficiencies) also known as Beta-oxidation defects, are a distinct type of organic acid disorder, characterized by hypoketotic hypoglycemia, hyperammonemia, and cardiomyopathy, and may present clinically with Reye’s syndrome. Medium-chain acyl-CoA dehydrogenase deficiency (MCAD) is among the most common of all IEMs and may account for 5% of SIDS cases.
Primary Lactic Acidoses (e.g., pyruvate dehydrogenase, pyruvate carboxylase and cytochrome oxidase deficiencies) present with severe lactic acidosis.
Aminoacidopathies (e.g., phenylketonuria, hereditary tyrosinemia, nonketotic hyperglycinemia, maple syrup urine disease [MSUD] and homocystinuria) may have similar presentation to the organic acidemias, but are a very heterogeneous group of disorders. Hereditary tyrosinemia can present in the neonate with a bleeding diathesis due to liver disease, or later in infancy with a renal Fanconi syndrome. The severe form of nonketotic hyperglycinemia presents as unremitting seizures with hypotonia and