A research including most disorders concerned with the inborn (neonates) including: Malnutrition / Nutrition disorders Congenital renal disorders Inborn metabolic errors congenital liver disorders (Cigler Najar syndrome - Rotor syndrome - Dubin johnson syndrome) and others ...

1. Clinical Biochemistry
In pediatrics

3. Clinical Biochemistry
• Clinical Biochemistry is a branch of medicine based on principles of
biochemistry and metabolism, human health and disease. The
Medical Biochemist is a specialist in laboratory medicine, is trained in
the operation and management of medical biochemistry laboratories,
and is a consultant in all aspects of their use. The medical biochemist
directs clinical laboratories, consults, diagnoses and treats patients
with a variety of metabolic disorders and biochemical abnormalities.

4. Pediatrics
• Pediatrics is the branch of medicine dealing with the health and medical care
of infants, children, and adolescents from birth up to the age of 18. The
word “pediatrics” means “healer of children” .

6. Good nutrition is essential for the growth and development that occurs during
an infant’s first year of life. When developing infants are fed the appropriate
types and amounts of foods, their health is promoted. Positive and supportive
feeding attitudes and techniques demonstrated by the caregiver help infants
develop healthy attitudes toward foods, themselves, and others.
Malnutrition in children:
Malnutrition generally refers both to undernutrition and overnutrition, but the
term is most commonly used to refer solely to a deficiency of nutrition. It’s
caused mainly by poor inadequate diet and disease states. Malnutrition in
children may lead to:
1-Stunting
2-Wasting
3-Underweight
4-Marsmus
5-Kwashiorker

7. 1-Stunting
• Characterized by a too
short body for age,
impaired physical and
mental development and
increased susceptibility
to disease and infection.

8. 2-Wasting
Wasting (too thin for height) , Wasting results from an acute shortage of food
and it is reversible with re-feeding. It has a relatively high mortality rate.
3-Underweight
A combination of wasting and stunting .
4-Marasmus
Severe weight loss due to inadequate diet deficient in all nutrients. The child
become extremely emaciated (fat & muscle tissue grossly reduced), having thin
flaccid skin hanging in loose folds “old man’s appearance”. There is frequent
association with dehydration, alertness & irritability.

9. 5-Kwashiorkor
• Bilateral pitting edema, beginning in the
lower legs and feet, can become more
generalized (hands and arms, “moon
face”). Occurs due to diet deficient in
protein. Characterized by bloated
appearance due to water accumulation
(edema), Reduced fat muscle tissue,
Skin lesions and hypo-pigmentation.

11. A) Disorders in carbohydrates metabolism
1-Glycogen Storage Disorders
2-Lactose Intolerance
3-hereditary Fructose intolerance
4-Favism or Primaquine sensitivity
5-Diabetes Mellitus

12. 1- Glycogen Storage Disorders
Defects in the enzymes that are responsible for either glycolysis or glycogenolysis → ↑ storage of either normal or
abnormal glycogen .
• Type I (Von Gierke's disease): Glucose-6-phosphatase deficiency.
Leads to: hepatomegaly- severe fasting hypoglycemia - mild ketosis - severe hyperlipidemia - hyperuricemia - lactic
acidosis, anemia and failure to thrive.
• Type II (Pompe's disease): Lysosomal acid maltase deficiency.
Leads to: Hypertrophic cardiomyopathy – macroglossia and failure to thrive.
• Type III (Cori's disease): Glycogen debrancher deficiency.
Leads to: Generalized muscle weakness and cramps – hepatomegaly - possibly cirrhosis (ascites, splenomegaly)
• Type IV (Andersen's disease): Glycogen branching enzyme deficiency.
Leads to Proximal myopathy - hepatomegaly - possibly cirrhosis (ascites, splenomegaly) .
• Type V (McArdle's disease): Muscle phosphorylase deficiency.
Leads to: Generalized muscle weakness - exercise intolerance - rhabdomyolysis – myoglobinuria .

13. 2- Lactose intolerance
Lactose intolerance is the body’s inability to digest lactose, a sugar found in milk and other dairy products. Due
to Lactase enzyme deficiency. Because of this, lactose cannot be absorbed and the metabolism of this sugar produces
uncomfortable gas and bloating.
Congenital Lactase Deficiency is a life-threatening medical emergency that is usually detected soon after birth. These
babies cannot digest lactose, and may exhibit: severe diarrhea, bloating, lack of weight gain or weight loss, and
dehydration. These babies cannot breastfeed or drink cow’s milk based formula, but need a formula free of lactose.
3-Hereditary fructose intolerance
Hereditary fructose intolerance (HFI) or fructose poisoning is a hereditary condition caused by a deficiency of
liver enzymes that metabolize fructose. It is also known as hereditary fructosemia. Caused by aldolase-B enzyme
deficiency , which converts fructose-1-phosphate to DHAP and glyceraldehyde. This means that fructose-1-phosphate
will be accumulated without further metabolism. In addition, Aldolase A plays an important role in gluconeogenesis.
But, glucose may still be released through the breakdown of glycogen. Although, it cannot be synthesized from
gluconeogenesis, resulting in severe hypoglycemia.
Symptoms: Hypoglycemia, vomiting, abdominal pain, hemorrhage, hepatomegaly, jaundice, liver failure, renal failure
and death.
Patient should eat Fructose-free diet.

14. 4-Favism or Primaquine sensitivity
Favism is a hemolytic disease due to deficiency of glucose-6-phosphate dehydrogenase enzyme. This
enzyme is linked to X chromosome so it’s more common in males than females.
Favism leads to acute, massive intravascular hemolysis. Its main clinical features are:
-Acute back and/or abdominal pain.
-Acute pallor due to anemia.
-Hemoglobinuria causing the passage of dark or orangey-yellow urine.
-Jaundice.
-Gallstones and splenomegaly due to recurrent episodes of hemolysis.
Patients should avoid ingestion of broad beans.
Drugs like; Primaquine, Niridazole , Nitrofurans , Quinolones , Chloramphenicol , Sulfonamides
, Methylene blue , Dapsone , Para-amino salicylic acid should be avoided.

15. 5-Diabetes Mellitus
• Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes, rare disease, which can
occur in the first 6 months of life. Infants with NDM do not produce enough insulin, leading
to an increase blood glucose. In about half of those with NDM, the condition is lifelong and
is called permanent neonatal diabetes mellitus (PNDM). In the rest, the condition is
transient and disappears during infancy but can reappear later in life - transient neonatal
diabetes mellitus (TNDM). Neonatal diabetes is now understood to arise from mutations in
genes that play critical roles in the development of the pancreas, of β-cell apoptosis and
insulin processing and the regulation of insulin release . Majority of the cases present
decreased subcutaneous fat, and low or undetectable C-peptide levels.
• Clinical manifestations at the time of diagnosis include intrauterine growth retardation
(IUGR), hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to
thrive.

16. B) Disorders in amino-acid metabolism:
1-Phenylketonuria
2-Tyrosinemia

17. 1-Phenylketonuria
One of the most frequent metabolic disorder associated with amino acid enzymatic disturbance,
caused by inborn deficit of phenyl alanine hydroxylase (PAH). It’s an Autosomal recessive
disease.
The accumulation of phenylalanine which is trans-aminated to phenylpyruvate. Both,
Phenylalanine and phenylpyruvate are very toxic with a predilection to the central nervous system.
Child looks normally at birth If left untreated PKU leads to: Severe brain damage and intellectual
disability - Seizures - Spasticity - Albinism (fair skin and hair) – mouse’s urine odor “Musty odor”
- Microcephaly - Eczema and Behavioral disorders.
Phenylalanine-restricted diet is the only and fully effective treatment option.
2-Tyrosinemia
Tyrosinemia 1 occurs when an enzyme, called fumarylacetoacetase (FAH), is either missing or not
working properly. So, tyrosine isn’t broken down. Tyrosine and other harmful substances then
build up in the blood. One of these substances is called succinylacetone. When it builds up in the
blood, it causes serious liver and kidney damage. It may also cause episodes of weakness or pain.

18. C) Disorders in lipid metabolism
Familial hypercholesterolemia (FH):
A high cholesterol concentration in the blood caused by an inherited genetic defect. Leads
to early development of atherosclerosis and coronary heart disease. The disease is
transmitted from generation to generation in such a way that siblings and children of a
person with FH have a 50% percent risk of having FH.
Early detection and treatment with hydroxy-methyl-glutaryl coenzyme A (HMG CoA)
reductase inhibitors (statins) has been shown to reduce morbidity and mortality in those
with heterozygous FH (reduction in LDL receptors). LDL apheresis and liver
transplantation are treatment options for individuals with homozygous FH (Complete
absence of LDL receptors).

20. The most common congenital disorder of live in neonates is the accumulation of
bilirubin (Hyperbilirubinemia).
When red blood cells break down, a substance called bilirubin is formed. Babies
are not easily able to get rid of the bilirubin and it can build up in the blood and
other tissues and fluids of the baby's body. This is called hyperbilirubinemia.
Because bilirubin has a pigment or coloring, it causes a yellowing of the baby's
skin, eyes, and other tissues. This is called jaundice. The most common reasons
are:
1-Crigler-Najjar syndrome.
2-Gilbert syndrome.
3-Dubin-Johnson syndrome.
4-Rotor syndrome.

21. 1-Crigler-Najjar syndrome:
It’s an autosomal recessive disorder in which patients have no UGT1A1 gene
activity ,“UDP-glucuronyl transferase 1 member A1”, (an enzyme that conjugates
bilirubin with glucuronic acid). So the unconjugated bilirubin backs up into the
blood, producing severe jaundice and icterus. It’s a rare syndrome.
2-Gilbert syndrome:
It’s a common syndrome. It can be autosomal recessive or autosomal dominant
depending on the mutated genes. Patients have a decreased activity of UGT1A1.
Patients usually have only mild unconjugated hyperbilirubinemia and there is no
clinical consequence (other than an increased sensitivity to drugs that are
metabolized by UGT1A1 and the anxiety that occurs when your skin turns yellow).

22. 3-Dubin-Johnson syndrome:
This one is an autosomal recessive disorder in which patients have an increase
in conjugated bilirubin in the blood. It’s caused by a defect in secretion of
bilirubin glucuronides across the canalicular membrane (patients are missing a
canalicular protein that transports bilirubin glucuronides into bile). The liver
looks darkly pigmented because of coarse granules within the hepatocyte
cytoplasm. Most patients are
asymptomatic .
4-Rotor syndrome:
Another autosomal recessive disorder in which patients have an increase in
conjugated bilirubin in the blood. The exact molecular defect is unknown – but it
seems these patients have multiple defects in hepatocyte uptake and excretion of
bilirubin pigments. The liver looks normal, and as in Dubin-Johnson syndrome,
most patients are asymptomatic .

24. Nephrotic Syndrome
The nephrotic syndrome (NS) is characterized by a triad of massive proteinuria,
hypoalbuminemia and hyperlipidemia (serum cholesterol >200 mg/dl ) . Other
supporting characteristics include the presence of edema and a raised β2
globulin on serum electrophoresis, although these are not essential for the
diagnosis. In physicians managing young children in whom 24 hour urine
collections are difficult, the Children’s Nephrotic Syndrome Study Group
Consensus Conference recommended the use of the protein: creatinine ratio on a
spot early morning sample of urine with a urine protein: creatinine (Up/Ucr)
ratio ≥2.0.

25. • Congenital nephrotic syndrome (CNS) is a rare form of nephrotic syndrome
(NS) that presents at birth or within the first three months of life. It is due in
most cases to genetic defects in the components of the glomerular basement
membrane. NS presenting after three months up to one year of age is called
infantile NS. The precise diagnosis of the glomerular lesion is based on
clinical, laboratory and histological criteria.
• CNS in its most severe form presents with anasarca (generalized edema),
severe proteinuria and severe hypoalbuminemia. Presence of extra-renal
malformations may point to syndromic forms of CNS. These include genital
abnormalities, eye defects and neurological disorders. Cardiac
ventricular hypertrophy without structural defects is common.
At the time of diagnosis blood urea and serum creatinine are
usually normal but kidney failure develops depending on etiology.

27. This research has been done by:
Alaa ElSayedElBadrawy