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
These 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.
Example: Methylmalonic or propionic acidemia, multiple carboxylase deficiency
These are 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.
Example: Short, medium, and long- chain acyl-CoA dehydrogenase deficiencies
These 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 hiccoughs. MSUD classically presents at the end of the first week of life with feeding difficulties, lethargy, coma, seizures and the characteristic odour.
Example: Phenylketonuria, hereditary tyrosinemia, nonketotic hyperglycinemia, maple syrup urine disease [MSUD] and homocystinuria
These defects result from the inability to detoxify nitrogen and are characterized by severe hyperammonemia and respiratory alkalosis, with a typical onset after 24 hours of age.
Example: Citrullinemia, ornithine transcarbamylase deficiency, and arginosuccinic aciduria.
There are a heterogeneous group caused by inability to metabolize specific sugars, aberrant glycogen synthesis, or disorders of gluconeogenesis. They may manifest with hypoglycemia, hepatosplenomegaly, lactic acidosis or ketosis.
Example: Galactosemia, hereditary fructose intolerance, fructose 1, 6-diphosphatase deficiency and the glycogen storage diseases
As per recent data 140 million children are born every year around the world, out of which 4 million children are born with some congenital problem of which thousands die of definable and non-definable reasons, referred to as Sudden Infant Death Syndrome, out of which at least 25-30% babies are expected to have Inborn Error of Metabolism. Recent data suggest that the overall incidence of metabolic disorder around the world is a good, 1:1350. Universal screening for metabolic disorders is mandatory in US, Europe and many other countries across the world. Though screening is a cost-intensive exercise, the benefits far exceed the costs as it helps in reducing the mortality & morbidity of the disease.
Screening is a process of filtration. Today, neonatal screening is the best known and most widely used genetics-related preventative paediatric public health initiative in the world. About 5 to 15% of all sick neonates in NICU are expected to have some Inborn Error of Metabolism, which may be transient or permanent.
Child mortality is a core indicator for child health and well-being. At the Sustainable Development Summit on 25 September 2015, UN Member States adopted the 2030 Agenda for Sustainable Development, which includes a set of 17 Sustainable Development Goals (SDGs). In 2013, neonatal mortality contributed to 68% of all infant deaths in India, and it will continue to represent an increasing proportion of child deaths. If India is to achieve its SDG targets across gender, wealth and caste, it needs more attention directed towards infant and maternal health policies, or 2030 will–once again–see India falling short of its health targets. To achieve this goal India not just requires Screening but a ‘Program’ including genetic testing support.
There are about 27 million births in India annually, of which 8 lacs are born with congenital malformation, 3.5 lacs with glucose 6 phosphate deficiency (G6PD), 25,000 with metabolic disorders, 20,000 with Down Syndrome, 15,000 with congenital hypothyroidism, 14,000 with thalassemia and 5,000 with sickle cell anemia. Screening of cases of mental retardation revealed that 5.75% cases were due to various IEMs. This makes the case for routine universal NBS in India. Considering the available Indian data, there is a need for universal newborn screening for all newborns in India.