The diagnosis of IEM in critically ill newborns requries a paediatricians - neonatologist , experienced in diagnosing and managing IEMs along with a dedicated laboratory , which is doing these biochemical investigations and standerdaises & upgrades tests on regular basis.
Over 400 human disease due to inborn errors of metabolism are now recognized , and this number is increasing as new concepts and technique become available for identifying biochemical phenotypes. However the incidence of inborn errors may well be underestimted , because diagnostic errors are frequent. Despite the relative abundances of new case report , there is considerable evidence that many of these disorders remian undetected or misdiagnosed.
A number of factors conspire to make the clinical diagnosis of IEM difficult. Because the individual IEMs are rare , many physicians do not consider them in acute situations until more common conditions have been ruled out. More over blood and urine samples may be unrevealing unless collected at the right time in relation to the acute illness , because many disorders affecting IEM produce only intermittent abnormalities.
For many neonates with IEM there is now a potential for survival and even normal development. This depends , however , on prompt recognition and treatment. Diagnostic accuracy is also necessary for further management including genetic counseling and prenatal diagnosis. The detection of IEM relies on a high index of clinical suspicion and co-ordinated access to specialized laboratory services. Biochemical analysis forms the basis of the ultimate diagnosis of inherited disorders. The underlying defect can be investigated at three different levels : the metabolite level , the enzyme level , and in a limited but growing number of disorders , the DNA level.
Great strides have been made in recent years in the diagnosis and treatment of IEMs. This expansion of knowledge, although providing critical insight into the normal metabolic processes in man , has served to bewilder the clinician responsible for the recognition and diagnosis of these disorders. He or she is often at a loss when confronted with a sick infant suspected of having a metabolic disorder. In fact he or she lacks the awareness.
Manifestations of IEMs , whether overt and life threatening or more subtle , are often present in the neonatal period. The significance of the precise diagnosis of metabolic disease , when possible cannot be overemphasized. Increasingly these disorders being successfully managed medically , and when treatment means the prevention of significant mental retardation or death, even when numbers are small, it is clearly worth pursuing.
There are few situation in medicine as acutely stressful as the percipitare deterioration of a previously healthy newborns infant , coupled with the recognition that , irrespective of the cause , delay in recognition and initiation of appropriate management often leads to death or irreparable brain damage. Severe illness in the newborn , regardless of the underlying cause , tends to manifest itself in a rather stereotypic way with relatively nonspecific findings , such a poor feeding, drowsiness lethargy , hypotonia , and failure to trive. Because inherited metabolic diseases are individually rare , clinicians have a tendancy to pursue the possibility only after other more common conditions, such as sepsis, have been excluded. Further delay often occurs because the type of investigation required to make the diagnosis of inherited metabolic disease includes unfamiliar test which the clinician may feel uncomfortable interpreting owing to a general lack of confidence regarding metabolic problems.
Its absolutely essential that inborn errors of metabolism be considered along with and at the same time as common acquired conditons , such as sepsis , hypoxic - ischemic encephalopathy , intraventricular hemorrhage , intoxications , congenital viral infections , and certains types of congenital heart disease. Appropriate laboratory investigation , including some simple bedsides tests , such as urine tests for reducing substances and ketones, should be initiated without delay , even done at the bedsides if possible. Despite the apparent nonspecificity of presenting symptoms in neonates with inherited metabolic diseases , there are some features which increase the likelihood of an inborn error of metaboism.
For many of these disorders, the predominant clinical signs and symptoms are those of poor feeding and lethargy, the same general features seen in neonatal sepsis , a more common diagnosis in the newborn. For certain disorders, these are more specific findings that might provide a clue to the clinician , and it is more important to be aware of these. In general however it is the constellation of findings , that should alert the physician to the possibility of metabolic diseases.
Most of these disorders are autosomal recessive disorders :-
Many of the signs and symptoms associated with Inborn Errores of Metabolism may be typical of other more common disease. Neonates with IEM usually appear normal at birth , However , signs and symptoms such as lethargy , poor sucking and feeding , seizures and vomiting may develop as early as few hours after birth. ( Dr. Menkes )
If such inborn errors of metabolism are not detected in time , the ultimate sequele would be mental and neurological handicap. Only timely intervention will prevent such complication.
Not all the patients will have the M.R. or C.P., other complications known following I.E.M. are as follows :-
1. Developmental disability
2. Speech and language dealy
3. Behavioural problems.
4. Attention deficit disorders.
5. Proximal Muscule weakness ( MCAD def. )
6. Chronic seizures disorders.
7. Failure to thrive.
These disorders are seen commonly amongest I.E.M.s in critically ill newborns.
Transient I.E.M.s :-
There are some transient I.E.M.s which may be quite serious in a given newborn and may lead to death, but if treated properly and if the crisis is tided over, the recovery is well known and they usually donot lead to life long problems.
1. Transient diabetes mellitus of newborn.
2. Transient hyperammonemia of the newborn.
3. Transient tyrosinemia of newborns ( especially the preterms )
4. Some varieties of Urea Cycle defects.
5. Transient Nonketotic Hyperglycinemia of newborn.
There are certain situations, when IEMs may be precipitated in a otherwiase healthy infant :-
1. Weaning of food ( introduction of new food items e.g. - fruits, nonveg items etc. )
2. Introduction of milk, even in newborn period.
3. Infections and fever.
4. Fasting 9 especially in older children who pay less attention to food while engaged in interesting games and continues to play.
5. Anesthesia and surgery.
6. Drugs , when child has G 6 PD deficiency or Porphyria.
There are certain IEM disorders in newborns which may mimick infection or may be associated with infections.
IEM presenting with as infection or associated with infection.
1. Galactosemia ( GAL )
2. Adenosine deaminase deficiency ( SCID )
3. Purine nucleoside phosphorylase deficiency.
4. Methyl malonic aciduria ( MMA ).
5. Multiple carboxylase deficiency ( MCD )
6. Isovaleric aciduria ( IVA )
7. Glutaric aciduria ( GA II )
8. Nonketotic hyperglycinemia ( NKHG )
Metabolic investigations to be ordered in a case of neonatal metabolic disorder. Besides sepsis workup we advise :-
A. Routine Biochemical
1. Blood sugar
2. Sr. Calcium
3. Sr. Phosphorus
4. Sr. Magnesium
5. Sr. Electrolytes
6. Sr. Bicarbonate
7. Arterial blood gases
8. Bun / Creat
9. Sr. Uric acid
10. S.G.O.T. / S.G.P.T.
11. Sr. Bilirubin
12. Sr. Proteins
1. T3 , T4 , T.S.H.
2. Sr. Cortisol Level
3. Sr. A.C.T.H. Level
4. Sr. Insulin Level
5. Sr. Growth Hormone
C. Special Metabolities
1. Sr. Ammonia
2. Sr. Pyruvate
3. Sr. Lactate
4. C.S.F. - Lactate
5. Ur. M.R.S.T.
6. T.L.C. - Amino acid
7. T.L.C. - Sugar
8. T.L.C. - Organic acid
9. H.P.L.C. - Amino acid
10.H.P.L.C. - Organic acid
11.G.C.M.S - Urine
12.MS / MS