Download Genes and CHI

Royal Manchester Children’s Hospital
Genes and CHI
Congenital Hyperinsulinism (CHI)
Patient/Carer Information Booklet 4
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Mutation positive and mutation negative CHI
Genes are the ‘blueprints’ of who we are, as individuals. There
are many genes in the body and put together, they form the
genetic code. Mutations are ‘spelling mistakes’ or ‘faults’
in these genetic codes. There are several genes in the body
that help in controlling how insulin is made and pushed out.
‘Spelling mistakes’ in these genes can cause CHI. The two most
important genes, ABCC8 and KCNJ11 code for how the KATP
channel is put together. A fault in ABCC8/KCNJ11 means a fault
in the KATP channel. Other genes such as HNF4A, GLUD1 and
GCK may also occur, but are rare.
Gene mutations are found in about 40% of children with CHI. In
the rest, no mutations are found. This does not mean that your
child does not have a genetic cause. The absence of a known
mutation simply means that we do not have a known genetic
basis for the disease. In about half of children who do not have
a gene mutation, there is a good chance that the low sugars will
improve and these children will not require treatment in the
long run. However, it is also true that some children with gene
mutations also get better. The reasons for this improvement are
unclear.
How do we inherit CHI?
Although gene mutations are not found in every child with
CHI, it is generally believed that there is a strong genetic basis
for the occurrence of CHI. It is useful to understand how these
genes are inherited to understand how certain types mutations
go with certain types of CHI.
All of us have two copies of every gene in our body. We inherit
one copy of each gene from each parent. Some genetically
inherited diseases only require one copy of the gene from
either parent to be abnormal to cause the disease. This is called
dominant inheritance. Some conditions require both copies of
the gene to be abnormal. This is called recessive inheritance.
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Some people carry only one faulty gene, but the other copy
of the gene is normal, which compensates for the fault. These
people become carriers of the faulty gene, but do not have the
condition themselves.
Most mutations that cause CHI in the ABCC8/KCNJ11 area are
recessively inherited. If one mutation is inherited from each
parent, the child has two mutations, which causes diffuse CHI.
In contrast, if the child inherits the mutation from the father
only, there is a chance of having focal CHI. This will depend
on another event that might have happened in the child’s
pancreas, something called maternal ‘silencing’. In this event,
the good gene copy inherited from the mother is ‘silenced’ and
therefore unable to compensate for the mutation inherited
from the father. This maternal ‘silencing’ cannot be determined
by blood tests. It is only after surgery that this can be tested.
Fortunately, PET-CT scans can be done before surgery to
know whether or not a child has focal CHI. At surgery, the
doctors take a bit of the pancreas and examine this under the
microscope to confirm the diagnosis.
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Congenital Hyperinsulinism Specialist Nurses:
Monday – Friday 9 am to 5 pm
Lindsey Rigby:
(0161) 701 2460
Louise Bowden:
(0161) 701 0518
Endocrine Department:
Monday – Friday 9 am to 5 pm
Manchester:
(0161) 701 1675
Alder Hey:
(0151) 252 5281
Dietitians and speech and language therapists:
Monday – Friday 9 am to 5 pm
Manchester:
(0161) 701 2640
Alder Hey:
(0151) 252 5231
Psychology:
Monday – Friday 9 am to 5 pm
(0161) 701 4514
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Suggestions, Concerns and Complaints
If you would like to provide feedback you can:
• Ask to speak to the ward or department manager.
• Write to us: Patient Advice and Liaison Services, 1st Floor,
Cobbett House, Manchester Royal Infirmary, Oxford Road,
Manchester M13 9WL
• Log onto the NHS Choices website www.nhs.uk - click on
‘Comments’.
If you would like to discuss a concern or make a complaint:
• Ask to speak to the ward or department manager – they
may be able to help straight away.
• Contact our Patient Advice and Liaison Service (PALS) –
Tel: 0161 276 8686 e-mail: [email protected]. Ask for our
information leaflet.
We welcome your feedback so we can continue to improve our
services.
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TIG 37/15 Produced March 2015 Review Date March 2017 (SF Taylor CM15539)