Errors of metabolism (newborn screening) - Essay Example

(CPSP, n.d.) (Rinaldo, 1988) Various findings also suggets that this disease is genetically inherited via autosomal recessive pattern. Going deep into the molecular mechanisms of this enzyme’s expression, it was found that MCAD enzyme is expressed by ACADM(alias MCAD) gene located on chromosome 1p31. Due to a point mutation at position 985 on the gene, results is swapping of an adenine by a guanine, that results in replacement of a lysine by a glutamate residue in the protein leading to onset of disease.

(Grosse, 2006; Wang SS, 1999; Matsubura, 1990). Around 80% of European individuals have at least two copies of this mutation. (Wang SS, 1999). Considering high mortality rate of 20 to 25% in undiagnosed cases, this disorder was included in the list of newborn screening programmes. (Wilson, 1999) Variation in Symptoms and Prognosis The deficiency of this enzyme is characterised by symptoms such as hypoketotic hypoglycaemia, vomiting (Egidio RJ, 1989) and hypotonia progressing to coma. (BPSU, 2006).

Other symptoms include seizures, coma, residual neurological deficits. No symptoms are exhibited at birth, except for the case when newbron screening is conducted. The symptoms show up any time between teh age of three to twenty-months; in some cases, it may show up much later. Once it is successfully diagnosed, prognosis becomes much effective by administering the patient with adequate treatment regimes (Matern, 2013). Diagnosis Prenatal-testing: Prenatal testing includes molecular genetic testing that helps in early diagnosis of the disease and thus enable the parents to be mentally aware and cautious of their child’s health.

The first test includes the testing of analyses that include plasma acylcarnitines, urine organic acids and urine acylglycines. Biochemical diagnoses include the measurement of fatty acid ?-oxidation in fibroblasts as well as measurement of MCAD enzyme activity in fibroblasts and other tissues (Leydiker, 2011). Molecular Genetic testing comprises of two methods that include Targetted Mutation Analysis and Sequence Analysis. Targetted mutation analysis a.k.a Allele specific mutation analysis involves the testing of the mutations p.

Lys304Glu (985A>G) and p.Tyr42His (199C>T). Sequence analysis involves the testing of sequence variants may also include other mutations such as splice site mutations, non-sense and mis-sense mutations as well as small deletions/ insertions. This method does not target mutations identified by Targetted mutation analysis. Newborn- Screening: Newborn Screening differs from Pre-natal testing such that pre-natal testing is carried out during pregnancy and before the child’s birth, whereas the former involves the testing of the child’s health condition within first few days of birth (Matern, 2013).

Tandem mass spectrometry was developed by Millington et al, for analysis of acylcarnitines in blood collected from umbilical cord as well as neonatal blood. This method proved to efficient diagnostic tool to diagnose MCAD deficiency. The simplicity and speed of the method enabled its use in everyday neonatal screening of infants (Millington, 1990; Kennedy, 2010) This tool has been widely used for screening of MCAD and has proved to be a robust, efficient tool. Newborns who are MCAD deficient have higher octanoylcarnitine levels than normal individuals; this forms an effective screening test, and has helped to decrease mortality and