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Fifth stage 

Pediatric 

Lec-8

 

أوس

 

22/2/2016

 

 

Autosomal recessive inheritance 

Many hundred disorders resulting from this type of inheritance are known        

An affected individual is homozygous for the abnormal gene, having inherited an abnormal 
allele from each parent, both of whom are unaffected heterozygous carriers  

 

For two carrier parents, the risk of each child, male or female, being affected is 1 in 4 (25%) 

All offspring of affected individuals will be carriers 

 

Consanguinity 

It is thought that we all carry at least one abnormal recessive gene. Fortunately, our 
partners usually carry a different one. Marrying a cousin or other relative increases the 
chance of both partners carrying the same abnormal autosomal recessive gene, inherited 
from a common ancestor. A couple who are cousins therefore have a small increase in the 
risk of having a child with a recessive disorder 

 


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Racial factor: 

Recessive gene frequencies may vary between racial groups 

cystic fibrosis is common in north Europeans, sickle cell disease in black Africans and 
Americans, thalassaemias in Mediterranean or Asian ethnicity and Tay-Sachs disease in 
Ashkenazi Jews.  

 

 

Inborn errors of metabolism: 

Although individually rare, inborn errors of metabolism are an important cause of 
paediatric morbidity and mortality. The specialised nature of the diagnostic tests and 
subsequent management often means that these patients are managed in specialist 
centres. However, as the prognosis for most patients depends upon the speed of diagnosis, 
all doctors need to be familiar with their variable presentation and diagnosis. 

 

Presentation: 

An inborn error of metabolism may be suspected before birth from a positive family history 
or previous unexplained deaths in the family     

After birth, inborn errors of metabolism usually, but not invariably, present in one of five 
ways 


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1.  as a result of newborn screening, e.g. phenylketonuria (PKU), or family screening, e.g. 
familial hypercholesterolaemia  

2.  after a short period of apparent normality, with a severe neonatal illness with poor 
feeding, vomiting, encephalopathy, acidosis, coma and death, e.g. organic acid or urea cycle 
disorders  

3.  as an infant or older child with an illness similar to that described above but with 
hypoglycaemia as a prominent feature or as an ALTE (acute life-threatening episode) or 
near-miss 'cot death', e.g. a fat oxidation defect such as medium-chain acyl-CoA 
dehydrogenase deficiency (MCADD) 

4.   in a subacute way, after a period of normal development, with regression, 
organomegaly and coarse facies, e.g. mucopolysaccharide disease or other lysosomal 
storage disorder or with enlargement of the liver and/or spleen alone, with or without 
accompanying biochemical upset such as hypoglycaemia, e.g. glycogen storage disease  

5.   as a dysmorphic syndrome.  

 

Phenylketonuria: 

It is either due to a deficiency of the enzyme phenylalanine hydroxylase (classical PKU) or in 
the synthesis or recycling of the biopterin cofactor for this enzyme. Untreated, it usually 
presents with developmental delay at 6-12 months of age. There may be a musty odour .  

Many affected children are fair-haired and blue-eyed and some develop eczema and 
seizures. Fortunately, most affected children are detected through the national biochemical 
screening programme (Guthrie test). 

Treatment of classical PKU is with restriction of dietary phenylalanine, whilst ensuring there 
is sufficient for optimal physical and neurological growth. The blood plasma phenylalanine 
is monitored regularly. The current recommendation is to maintain the diet throughout life. 
This is particularly important during pregnancy, when high maternal phenylalanine levels 
may damage the fetus 

 

Galactosaemia:  

This rare, recessively inherited disorder results from deficiency of the enzyme galactose-1-
phosphate uridyl transferase, which is essential for galactose metabolism 

Presentation: 

 

When lactose-containing milk feeds such as breast or infant formula are introduced, 
affected infants feed poorly, vomit and develop jaundice and hepatomegaly and 
hepatic failure    


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Chronic liver disease, cataracts and developmental delay are inevitable if the condition 
is untreated. 

Treatment: 

Management is with a lactose- and galactose-free diet for life. Even if treated early, there 
are usually moderate learning difficulties (adult IQ 60-80). 

 

Glycogen storage disorders: 

These mostly recessively inherited disorders have specific enzyme defects which prevent 
mobilisation of glucose from glycogen, resulting in an abnormal storage of glycogen in liver 
and/or muscle. There are nine main enzyme defects 

The disorder may predominantly affect muscle (e.g. types II, V), leading to skeletal muscle 
weakness. In type II (Pompe's disease) The heart is severely affected, leading to death from 
cardiomyopathy. In other types (e.g. I, III) the liver is the main organ of storage, and 
hepatomegaly and hypoglycaemia are prominent  

Management is to maintain blood glucose by frequent feeds or by carbohydrate infusion 
via a gastrostomy or nasogastric tube in infancy. In older children, glucose levels can be 
maintained using slow-release oligosaccharides (corn starch 

 

 




رفعت المحاضرة من قبل: Abdalmalik Abdullateef
المشاهدات: لقد قام 12 عضواً و 136 زائراً بقراءة هذه المحاضرة








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