Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT05977972 |
| Other study ID # |
Neonatal hypoglycemia |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 1, 2023 |
| Est. completion date |
August 1, 2024 |
Study information
| Verified date |
July 2023 |
| Source |
Assiut University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Inborn errors of metabolism (IEM) are disorders in which there is a block at some point in
the normal metabolic pathway caused by a genetic defect of a specific enzyme. The number of
diseases in humans known to be attributable to inherited point defects in metabolism now
exceeds 500.While the diseases individually are rare, they collectively account for a
significant proportion of neonatal and childhood morbidity and mortality. Diagnosis is
important not only for treatment and prognostication but also for genetic counselling and
antenatal diagnosis in subsequent pregnancies.
Description:
Inborn errors of metabolism (IEM) are disorders in which there is a block at some point in
the normal metabolic pathway caused by a genetic defect of a specific enzyme. The number of
diseases in humans known to be attributable to inherited point defects in metabolism now
exceeds 500.While the diseases individually are rare, they collectively account for a
significant proportion of neonatal and childhood morbidity and mortality. Diagnosis is
important not only for treatment and prognostication but also for genetic counselling and
antenatal diagnosis in subsequent pregnancies.So ,the main problems facing the physician
caring for a sick newborn infant are to know when to consider the possibility of a metabolic
disorder, what to do to determine quickly and efficiently whether a child has a metabolic
disease, and how to treat the patient until a diagnosis is established.
One of the clinical presentations that raises red flags of inborn error of metabolism is
persistent or recurrent hypoglycemia. However recognizing hypoglycemia in the newborn may be
difficult, because the symptoms of hypoglycemia (i.e., lethargy, poor feeding, hypothermia,
and seizures) are non specific. Frequent blood sugar determinations are often required to
confirm the suspicion of hypoglycemia. Because inborn errors of metabolism are a relatively
infrequent cause of neonatal hypoglycemia, other diagnostic possibilities should be
investigated concurrently.
The first possibility to consider is neonatal stress secondary to perinatal asphyxia,
hypothermia, or intrauterine malnutrition (e.g., placental abnormalities, prematurity,
multiple gestations). The second consideration is the possibility of a hormonal abnormality
affecting insulin regulation. The inborn errors of metabolism associated with insulin
dysregulation include 3-hydroxacyl-CoA dehydrogenase (HADH ) deficiency and
hyperammonemia/hyperinsulinism (HA/HI) syndrome, both of which are diazoxide-responsive.The
third possibility to consider is a malformation syndrome, specifically including those
syndromes associated with hormonal dysregulation such as Beckwith-Wiedemann syndrome. The
fourth possibility is that the patient has a severe hepatocellular or cirrhotic liver disease
that leads non specifically to fasting hypoglycemia.
Hypoglycemia may be associated with five categories of inborn errors of metabolism: fatty
acid oxidation defects gluconeogenesis defects, glycogen storage diseases, ketogenesis
defects, and organic acidemias . The diagnostic approach to hypoglycemia, therefore, must
give consideration to entities belonging to each of these categories. Usually, Krebs cycle
defects and mitochondrial disorders do not produce hypoglycemia, but these defects should be
considered when other evidence points in their direction.
The diagnostic approach must quickly narrow the field of possible diagnoses so that specific
treatment can be instituted. The classic approaches to the differential diagnosis of
hypoglycemic disorders in children are the fasting study and specialized challenge tests.
These studies are, however, not feasible in newborn infants because of the significant risks
and technical difficulties associated with performing such studies and because of the lack of
control data derived from normal neonates. Alternatively, efforts to determine the cause of
hypoglycemia in the newborn infant should include hormonal and biochemical studies before and
after feeding and especially during an acute episode of hypoglycemia. Definitive diagnosis
might have to be postponed several months until the child is old enough to tolerate a formal
fasting study or specialized in vitro cell studies.
An algorithm for diagnosing the disorders that cause neonatal hypoglycemia can be generated
from the results of the following studies: blood electrolytes and pH, plasma and urinary
ketones, plasma free fatty acids, blood lactate and pyruvate, blood ammonia, liver function
tests, plasma and urinary carnitine and acylcarnitine analysis, and urinary organic acids. A
specific diagnosis might not be made by these studies, but they are necessary for providing a
provisional diagnosis that can be confirmed by specific enzyme analysis.
