what will happen if genes of thal a2 and hbd will come together in the newborn

HI, I AM IN MUMBAI,INDIA ,IN THE YEAR 2001 WHILE MY WIFE WAS PREGNANT WITH 7 MONTH'S ,PERIOD  SO DURING DIAGNOSE, SHE CAME TO KNOW THAT SHE HAS MINOR THALASSAEMIA , THE DOCTOR SUGGESTED HAEMOGLOBIN  ELECTROPHPRESIS TEST TO MY WIFE,  HER REPORT OF THE TEST WAS REAVLED AS UNDER:

FOETAL HAEMOGLOBIN                       : 0.6%

HAEMOGLOBIN ELECTROPHORESIS   : A+A2 PATTERN SEEN

HAEMOGLOBIN A2 FRACTION            : 5.0%
(COLUMN CHROMATGRAPHY)

ABNORMAL HAEMOGLOBIN               : ABSENT

SICKLE CELL TEST                                   : NEGATIVE


IMPRESSION                                         : B THALASSAEMIA  (THALASSAEMIA MINOR)


SO IMMEDIATELY DOCTOR HAD TOLD ME TO GO FOR CERTAIN BLOOD TEST FOR KNOWING THAT IS THERE ANY THALASSAEMIA MINOR?

SO I HAD GONE FOR THE ABNORMAL HAEMOGLOBIN STUDY

THE STATICS OF MY REPORT ARE AS UNDER :

TYPE OF HB                             RESULT                    NORMAL VALUE

HB    -      F %                :        0.8                             LESS THAN 2.0
 
HB    -      A2 %              :        2.1                            LESS THAN 3.5
 
HB    -      D                    :        24.                             NOT DETECTABLE

HB    -      S                    :       NOT DETECTED        NOT DETECTABLE

HB    -      C                    :       NOT DETECTED        NOT DETECTABLE

RETICULOCYTE               :       0.8%

SICKLING PHENOMENON   :       NEGATIVE

OTHER ABNORMALITY     :        -------------

IMPRESSION                   :      HETEROZYGOUS    FOR HB - D

AFTER OBSERVING THIS REPORT THE DOCTOR TOLD ME THAT NOW THERE IS NO NEED TO WORRY BECAUSE YOU DON'T HAVE THE THALASSAEMIA MINOR SO THE NEW BORN CHILD WILL MAXIMUM TO MAXIMUM WILL HAVE THALASSAEMIA MINOR

AND THAN MY WIFE DELIVERED A GIRL CHILD SHE IS NOW 10 YEARS OLD , HEIGHT 128 CMS,WEIGHT 29KG AND HAVE BEEN NEVER DIGNOISED FOR ANY TYPE OF DISEASE IN FACT NEVER ANY CLINICAL ISSUE HAS ACCRUED FOR WHICH SHE HAVE REQUIRED ANY MEDICAL HELP.
WHEN SHE WAS 6 AND HALF YEARS OLD AND WE HAD DONE HER
HAEMOGRAM TEST REPORT OF WHICH DONE ON SYSMEX KX-21-NORMAL VALUE ACCRDING TO SEX AND AGE

HER REPORT REVEALED AS UNDER:

   TEST                                                 RESULT                                      NORMAL VALUE

HAEMOBLOBIN                                     10.1     G/DL                          11.5-14.5     G/DL

TOTAL WBC COUNT                              8000    /CMM                       5000-14500 /CMM

DIFFERENTIAL LEUCOCYTE COUNT

POLYMORPHS                                      40         %                                 36-66   %

LYMPHOCYTES                                    48         %                                  37-47   %

EOSINOPHILS                                      09        %                                   UPTO 7  %

MONOCYTES                                       03        %                                 UPTO  10  %


SMEAR STUDY
--------------------
ON SMEAR         RBCS: MILDLY HYPOCHROMIC & MICROCYTIC
                        PLATELETS: ADEQUATE & NORMAL
                        PREMATURE CELLS : NOT SEEN
                        BLOOD PARASITES : NOT SEEN

RBC INDICES                               RESULT                                 NORMAL VALUE
------------------                            -----------------                            ------------------------

RBC COUNT                              5.38     M/UL                             4.0  -   5.3  M/UL

HCT                                        32.7     %                                  33   -  43   %

MCV                                        60.8   FL                                    76   -  90   FL

MCH                                       18.8  PG                                     25   -  31   PG

MCHC                                     30.9  G/DL                                  32   -  36  G/DL

RDW                                      10.2  %                                     11.5  -   15.0   %

PLATELETS COUNT                362000  /CUMM                          142000-524000 /CUMM[/b]
------------------------                      

       ANOTHER TEST REPORT OF MY DAUGHTER OF NORMAL AND ABNORMAL HAEMOGLOBIN QUANTIFICATION BY HPLC (BY BIORAD VARIANT)

    TEST                                        RESULTS                                     NORMAL VALUE
--------------                                   ------------------                                -----------------------

HBA (ADULT)                                 29.00   %       L (LOW)              94.30   -  98.50

HBA2 QUANTIFICATION                    3.20     %                                 1.50   -   3.70

HBS  (SICKLE)                                 0.00     %                                  0.00   -  0.00
 
FOETAL HB                                    6.00     %     H H (VERY HIGH)      0.00    -  2.00

SICKLING TEST                              NEGATIVE
(BY SODIUM DITHIONATE )

ABNORMAL HAEMOGLOBIN             HBD IS 61% OF TOTAL HAEMOGLOBIN

INTERPRETATION OF                    HP;C PATTERN IS SUGGESTIVE OF HBD DISEASE
CHROMATOGRAM                

SO HERE PLEASE LET ME ADVICE WHAT IS HBD61% HAS BEEN DETECTED TO MY DAUGHTER  SO IS IT A TYPE OF THALASSAEMIA IF YES THAN WHAT TYPE MINOR OR INTERMEDIA WHERE AS SHE IS HAVING A VERY NORMAL LIFE, IS THERE ANY PROBLE SHE MAY FACE IN THE FUTURE, DOCTOR ARE SAYING THAT SHE IS NOT HAVING THE  MINOR THALASSAEMIA BUT PROBLEM OF ANEMIA SHE HAS.

NOW AT THE PRESENT MOVEMENT MY WIFE IS AGAIN PREGNANT SINCE MY WIFE IS THAL. MINOR AND I HAVE BEEN DETECTED HBD  SO PLEASE ADVICE US THAT HOW MUCH POSSIBILITY IS THERE  THAT OUR NEW BORN CHILD WILL HAVE:

(1) THALASSAEMIA MAJOR/INTERMEDIA/MINOR/NORMAL  

(2)IF NEW BORN GETS BOTH THE GENES THAT IS THALASSAEMIA MINOR FROM MOTHER AND HBD FROM  FATHER  THAN WHAT WILL HAPPEN TO ITS HEALTH

(3) IS THERE ANY TEST BY DOING THAT WE CAN COME TO KNOW THAT WHAT EXACTLY OUR CHILD WILL HAVE LIKE THALASSAEMIA MAJOR/INFOMEDIA/MINOR/NORMAL AND WILL YOU SUGGEST US TO GO FOR THAT TEST AND IN THAT TEST WILL THERE BE ANY PROBLE OF LIFE TO THE NEW BORN OR TO MY WIFE.

PLEASE REPLY,

THANKS IN ADVANCE,

Your daughter appears to have Heterozygous Hemoglobin D/Beta (β)-thalassemia. This is a result of the mother carrying beta plus thal trait and you carrying HbD trait. I say beta plus because your daughter has HbA present and there would be none if your wife carrier beta zero. This condition manifests in a mild anemia, as noted in your daughter's Hb of 10. This is anemic but not serious. This is also as severe as this condition normally will be, and since it is the result of both parents passing on a gene defect, this means that your new child will be either like your 10 year old or not be affected much at all if only one or neither gene defect is carried.

http://health.utah.gov/newbornscreening/Disorders/English/HB/FactSheetProv_HBD_En.pdf

Heterozygous Hemoglobin D/Beta (β)-thalassemia:
Infants with heterozygous Hb D/β-thalassemia may be asymptomatic and have mild to moderate
hemolytic anemia depending upon the degree of β-thalassemia affecting the A gene. It usually develops
in the first few months of life as the amount of Hb F decreases and Hb D increases. Those with Hb
D/β+-thalassemia have some Hb A and are more likely to have mild to moderate anemia and a nonpalpable
spleen. Children with hemoglobin D/βº-thalassemia syndrome have no Hb A, exhibiting
symptomatic anemia with splenomegaly and may have a moderately severe clinical disorder. Because
RBC indices are abnormal in Hb D/β-thalassemia, iron deficiency may develop.
Essential Steps

You can check the status of the fetus later on during the pregnancy with an amniocentesis, but I see no reason for any obtrusive test. Your daughter would be considered thalassemia minor. She can expect a lifelong mild anemia and may find some benefit in certain vitamins and supplements, along with a nutritious diet. I do encourage folic acid as a supplement to help build healthy red blood cells. The traditional Indian spices used in cooking are known to be beneficial and are encouraged. Your new child will be either normal or thal minor. I see no reason for concern. Your doctor is correct to say thal minor at the most.

As a general point of interest in this combination, I do want to mention that if beta zero minor is combined with HbD, a more severe condition will be found, possibly leading to splenectomy and even occasional transfusion. The fact that in this particular case, there is an HbA level of 29% in the daughter shows that the mother is a beta plus thal carrier and not beta zero, as there would be no HbA in that case and the health would hinge on how much HbD and HbF was produced. I am happy to see that in this case it is the milder form.

first of all thank you very much for providing the great services to the human being sir your knowledge on the thal is more than the doctors .sir once again i am asking that are are sure that there is no need of amniocentesis test ? Because as you are advising that at the  most, maximum to maximum our new born child will have thal minor and not the thal intermedia or thal major, we also don't want the thal intermedia or thal major child.
secondly i would like to know that in the amniocentesis test can we come to know that our new born is normal/ thal minor/thal intermedia/thal major or we can come to know only about thal minor and thal major further can we come to know the count (precentage) of the deffected genes in the new born because it is the result of both parents passing on a gene since mother carrying  beta plus thal trait and you (father) carrying HbD trait.

hanks in advance.
 

I see no reason to do an amnio. Your daughter appears to carry the two thalassemia genes from the parents, both beta thal minor and HbD thal. The high HbF of 6% is typical for beta thal minor. The HbA2 level is normal and not usually seen with thal minors, where it is higher, as in your wife (5%). This is due to the effect of the HbD, which masks the presence of thal minor, but in this case, the HbF level is what would be expected if beta minor is present. The presence of HbA in your daughter shows that her beta gene cannot be zero, because the gene she received from you produces HbD and no HbA, so her HbA production has to come from the mother's gene, which means it has to be beta plus and not beta zero. Interestingly, since I last posted on this topic, we have a new member who does have HbD beta zero thal and still carries a good Hb level without transfusion. The HbD compensates for HbA, but it does break down sooner, sometimes causing some enlargement of the spleen. This is unlikely to be much, if any problem for your daughter. Your daughter already has the defective genes from each parent without any problem other than very mild anemia and any other children should be no worse.

I had previously mentioned that Hb lepore is sometimes seen with HbD, but there is no mention of any other hemoglobin variants in the tests, and there would be no HbA present if your daughter carried the lepore variation, so this seems impossible in this case.

OK FINE PLEASE REPLY FOR MY CURIOSITY THAT:

(1)WHAT IS THE DIFFERENCE BETWEEN CHORIONIC VILLUS TEST OR AMNIOTIC TEST OR BOTH
THE TEST ARE SAME ONLY THE NAMES ARE DIFFERENT?

(2)WHAT THESE TESTS SHOWS IN THEIR RESULTS?

(3)IS IT POSSIBLE THROUGH THESE TESTS THAT THE INFANT HAS GOT  MINOR / INTERMEDIA MAJOR THAL?

(4)HOW MUCH IS THEIR ACCURACY? ARE THESE TEST ARE 100% ACCURATE?

(5) DO THE REPORT OF THESE TESTS GIVE THE PERFECT RESULTS OF HAEMOGLOBIN I MEAN TO SAY PERCENTAGE/QUANTITY OF DIFFERENT DIFFERENT CONTENTS LIKE  HB F, HBA ,HB A2 , HBD ,HB,HBF,HB RETICULOCYTE, SICKLING PHENOMENON ETC.

(6) DO THESE TESTS CARRY ANY RISK TO THE INFANT OR MOTHER

(7) IS THE TESTS OF PARENTS ARE ALSO REQUIRED FOR COMPARING TO OR FOR KNOWING THE RESULT OF THESE TESTS ?

 PLEASE REPLY, THANKS

I can answer some of your questions on the testing as I have done both; an amnio and a CVS. 

A CVS is an earlier test done when the fetus is between 10-14 weeks. This is definitely a more invasive test as they will be gathering CELLS from the Chorionic villi.  These are tiny finger-shaped growths found in the placenta. The genetic material in chorionic villus cells is the same as that in the baby's cells. During CVS, a sample of the chorionic villus cells is taken for biopsy. 

The Amnio is usually done in the 4th to 5th month of pregnancy and this test takes fluid from the amniotic sac. 

The difference between both these test are as follows:
- CVS can be done earlier and this is beneficial for the mother as attachment to the baby grows so quickly.
 
- CVS was at one point considered to have a higher risk of miscarriage - however, these days this test is performed so often that the risks are the same as having an amnio. 

-CVS test can be done via the abdomen or via the cervix. 

-the pain associated with this is pretty minimal.  I have heard some people say they experience a slight cramping feeling.  This test for me was done through the abdomen and I personally did not feel anything during the process.

-The Amnio is done through the abdomen only.  It is supposed to be a lower risk for miscarriage however, as I explained both tests seem to be the same now.   The results just come a lot later and unlike a CVS this testing actually detects Spin bifida where as the CVS does not. 

-I would definitely recommend talking to your doctor about sending you to a center which specializes in these procedures.  2 years ago when I was sent to do my first CVS my doctor wasn’t comfortable for me going to the local hospital as they weren’t as experienced with CVS’s at the time.  This year I did go to the local hospital because they had been doing CVS’s often and were more comfortable.

As far as the other questions.  Yes, the test of the parent is required so that they are able to accurately look for and detect what they need from the sample.  They will also take blood from both or 1 parent at the time of the test to ensure that the sample they have taken is not contaminated with the mother’s cells.  This is done because when samples are taken it is possible for cells to be confused with that of the mother’s.

The test is about 98% accurate.  My test was sent to 2 labs to ensure accuracy.  However, I have heard of instances where the test was inaccurate.  Many times the inaccurate results are the ones that show the negative for thal major because it is a very difficult disorder to detect.  ESPECIALLY when they are unsure of the exact deletions. 

I hope that helps a bit.  TC and good luck!!

Thanks Cari, this is very informative 
Manal

DEAR SIR,

MY WIFE IS PREGNANT WITH 3-4 MONTH'S ,PERIOD  SO DURING DIAGNOSE, SHE CAME TO KNOW THAT HER HB IS VERY LOW SO THE  DOCTOR SUGGESTED HAEMOGLOBIN  ELECTROPHPRESIS TEST TO MY WIFE, AND IN THE REPORT IT IS DETECTED THAT SHE HAS MINOR THALASSAEMIA  HER REPORT OF THE TEST WAS REAVLED AS UNDER:

FOETAL HAEMOGLOBIN                       : 0.6%

HAEMOGLOBIN ELECTROPHORESIS   : A+A2 PATTERN SEEN

HAEMOGLOBIN A2 FRACTION            : 5.0%
(COLUMN CHROMATGRAPHY)

ABNORMAL HAEMOGLOBIN               : ABSENT

SICKLE CELL TEST                                   : NEGATIVE


IMPRESSION                                         : B THALASSAEMIA  (THALASSAEMIA MINOR)

SO IMMEDIATELY DOCTOR HAD TOLD ME TO GO FOR CERTAIN BLOOD TEST FOR KNOWING THALASSAEMIA MINOR IN ME ?

SO I HAD GONE FOR THE ABNORMAL HAEMOGLOBIN STUDY

THE STATICS OF MY REPORT ARE AS UNDER :

TYPE OF HB                             RESULT                         NORMAL VALUE

HB    -      F %                :        0.8                               LESS THAN 2.0
 
HB    -      A2 %              :        2.1                               LESS THAN 3.5
 
HB    -      D                    :        24.30                           NOT DETECTABLE

HB    -      S                    :       NOT DETECTED               NOT DETECTABLE

HB    -      C                    :       NOT DETECTED               NOT DETECTABLE

RETICULOCYTE               :       0.8%

SICKLING PHENOMENON   :       NEGATIVE

OTHER ABNORMALITY     :        -------------

IMPRESSION                   :      HETEROZYGOUS    FOR HB – D

NOW SIR ADVICE ME THAT ON THE BASIS OF THE ABOVEMENTIONED REPORTS IS THERE ANY POSSIBILITY THAT OUR NEW BORN CHILD WILL HAVE THAL MAJOR/INTERMEDIA

NOW HERE I WOULD LIKE TO KNOW HOW MUCH IS THE PERCENTAGE THAT OUR NEW BORN CHILD WILL HAVE THAL MINOR/MAJOR/INTERMEDIA

IS THERE ANY TEST,WHICH CAN DETERMINE THIS?

No worries for you , as you are not the THAL MINor , Baby will be effected only when both the parenets are Thal minor .

I have merged the two topics. The questions have all been answered. Please read the replies.

Hello,

Me and my wife are expecting our first child. Her POG is 17 Weeks + 3 days. Our HPLC report status is a follows

WIFE HPLC

Hb F            2.40 %     

PEAK 2        4.80 %

PEAK 3         4.60 %

Hb ADULT     82 %

Hb A2             5.00 %

Hb D(PUNJAB)  0.00

Hb Sickle          0.00

Hb C                 0.00

HB E                0.00

Hemoglobin       10.9 gm/dl

Interpretation : HPLC Findings are consistent with a Thalassemia trait/Minor.

HUSBAND HPLC

Hb F             < 1.00 %

Peak 2           2.60 %

Hb Adult        56.30 %

Hb A2            3.0 %

Hb D             40.7 %

others             7.20 %

Hemoglobin      15.40 g/dl

RBC Count        5.40 mill/mm3

PCV                    51.80 %

MCV                   95.90 fL

MCH                  28.50 pg

RDW                 13.50 %

Interpretation: HB D (PUNJAB) Trait (Heterozygous State). Hb A2 may be suppressed in HB D thus masking the presence of Beta Thalassemia Minor.


Based on the above results we also gone through a GENETIC ANALYSIS for HBB Gene Sequencing (ENST00000335295.4). Results of that are as follows:

Wife : was found to be heterozygous for variation c.27_28insG in HBB Gene and
Husband : was found to be homozygous for variation c.364 G>C in HBB Gene.

Details of Mutation: This variation has been reported in dbSNP, 1000 Genomes, ExAC and HGMD as disease causing respectively.

Methods : In the DNA sample extracted from EDTA Blood, HBB gene was amplified by PCR and was sequenced using Bidirectional Sanger Sequencing (Bigdye v3.1)

Now, I wanted to know, based on the above case history what are the chances of our baby to be Thal Minor/Thal Major/Thal Intermedia/Normal/HBD or any other problem?

Are there chances of any other problem to the child?   

We have been told to go for CVS to confirm, so Should we go for CVS to confirm this?

Our CVS is planned for tomorrow, and we want to avoid that looking at the Risks involved, but we also don't want our child to be suffer from any thalassemia problems.

PLEASE SUGGEST ASAP.

If the fetus carries both, it can result in a mild to moderate outcome for the baby. The child could be anywhere from thal minor to mild thal intermedia. Not a severe condition.

Thanks for replying.

What are the consequences of having mild to moderate thalassemia intermedia..? Will the child have normal growth..? At any stage will child require transfusion..?

Should we go for cvs to confirm?? And will cvs confirm thalassemia status clearly in the child..?  Please confirm

Your wife is thal minor, so that is what it would be like if the child had that phenotype. If it is a mild intermedia phenotype, the Hb would probably be in the 8-9 range, where transfusions are not needed, but anemia would definitely be present. There is a 25% chance the fetus will carry both genes. CVS isn't absolutely necessary, but it would do a lot to ease your minds during the pregnancy if you know what the fetus is carrying.