Hello XXXXXXX

Thanks for posting your query.

High bilirubin levels may be seen in physiological neonatal jaundice, persistent breast milk jaundice and in neonatal hepatitis (liver inflammation.)

But if low AAT levels are detected then further testing is required to confirm the type of AAT deficiency. These are genetic tests like AAT phenotyping and DNA testing for AAT gene variants.

Most likely your niece is suffering from AAT deficiency and cholestatic jaundice and not physiological jaundice.

AAT deficiency is a genetic disorder which predisposes an infant to either lung or liver disease in future.
But the effects of disease progression and severity are very variable in each patient.

So much so that only 10-20% infants with AAT deficiency have neonatal hepatitis with cholestatic
jaundice; others may have abnormal liver enzymes. A very small proportion (1-2%) of children
with AAT deficiency actually need a liver transplant due to cirrhosis in childhood. In the
remainder, liver abnormalities tend to diminish or disappear although mild hepatomegaly or mild
elevations in liver enzymes may persist.

So please do not panic though there is no absolute cure but nowadays many treatment modalities are available and complications are preventable.

Majority of infants do not develop liver failure, remember high bilirubin alone is not indicative of liver failure.

So do not lose hope and do continue the treatment and follow up with her doctor.

Hope I have answered your query. Please write back to me if you have any doubts.

Wishing your niece good health.

Regards,

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Hello.

Thanks for the follow up.

It is not easy to tell you the exact mechanisms without using medical jargon or without explaining the details of normal physiology of liver, but I will try my best to clear your doubts.

Answer 1.

AAT is a protein synthesized by liver cells and other blood cells like monocytes. Its' one of the major function is to inhibit an enzyme called neutrophil elastase which normally helps body to fight bacteria and sometimes cause inflammation. When there is AAT, deficiency or abnormal AAT the neutrophil elastase action goes unchecked and causes damage and inflammation to normal tissues like lung, skin liver.

In addition, this abnormal or misfolded AAT accumulates or sticks in liver cells and cause liver cells to be injured or die i.e. cirrhosis or liver failure. Cholestatic jaundice means jaundice due to bile stasis i.e. inability for normal bilirubin excretion in a damaged liver.

The treatment is just symptomatic and sometimes surgical drainage and lastly liver transplant.
There is no cure as of now but genetic and biochemical research to replace diseased AAT gene or
protein are in progress.

Answer 2:

Three AAT genes regulate the synthesis of this protein. In patients with AAT deficiency, there is defect in the genes, which causes decreased, or no AAT protein or misshapen abnormal AAT
protein. Yes, the prognosis is better in XXXXXXX variant than sz or zz out of many variants.

Null null genotype means no normal AAT found in circulation making lung disease worse.
However, even among same genotypes the prognosis is very variable from patient to patient.

Answer 3:

Yes, parents should be tested in similar manner i.e. for AAT levels and genetic tests. Since this is definitely a hereditary disorder.

Hope I have cleared your doubts.

For detailed study, you may refer to WWW.WWWW.WW or similar sites for patients of AAT deficiency.

Regards.

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