Re: R: Re: Alpha Thalassemia
From: The-Hung Bui (The-Hung.Bui@ks.se)
Tue Jan 16 09:08:08 2001
Received: from atd.hazara.net.pk ([203.135.2.161])
by mail.medispecialty.com (8.9.3/8.9.3) with ESMTP id KAA16531
for <ultrasound@obgyn.net>; Tue, 16 Jan 2001 10:07:53 -0600
Received: from atd.hazara.net.pk ([203.135.2.180])
by atd.hazara.net.pk (8.9.3/8.9.3) with ESMTP id VAA18978
for <ultrasound@obgyn.net>; Tue, 16 Jan 2001 21:11:25 +0500
Message-ID: <3A6468F3.5839CC12@atd.hazara.net.pk>
Date: Tue, 16 Jan 2001 20:29:55 +0500
From: Dr Fazeel uz Zaman <fazeel@atd.hazara.net.pk>
X-Mailer: Mozilla 4.7 [en] (Win95; I)
X-Accept-Language: en
MIME-Version: 1.0
To: ultrasound@obgyn.net
Subject: Re: Alpha Thalassemia
References: <20010115.223810.-3807149.2.tjdubose@juno.com>
Content-Type: text/plain; charset=us-ascii
Content-Transfer-Encoding: 7bit
Terry,............I agree, and couldn't have said better than you.
Thank you Dr. Smeltzer and Terry :-)
Dr. Fazeel
Terry J DuBose wrote:
> Dr. Smeltzer, this is very interesting and exciting... what a wonderful
> thing for you to be able to share your literature search with someone
> with an on going case in Taiwan.
>
> Now, you say the VMax is 74... I did not see the numbers in the abstract,
> but do you know if that is the upper 95% confidence in the normal
> population? I assume this is due to the reduced viscosity with anemia.
>
> Thanks for this... good job.
>
> Peace, Terry J DuBose, M.S., RDMS
> Little Rock, ARkansas USA
>
> On Mon, 15 Jan 2001 22:18:02 -0600 "James S. Smeltzer, MD"
> <gaperina@mindspring.com> writes:
> > Hi,
> >
> > Regarding testing for fetal anemia, Mari has shown that the MCA
> > maximum
> > velocity is strongly predictive of hematocrit. Weekly testing may be
> > required, though. Last week I transfused a fetus with early
> > hydrops, an MCA
> > VMax of 74 (high) and a hemoglobin of 3 at 25 weeks, one week after
> > there
> > were no signs of hydrops and the MCA VMax was 42 (upper normal).
> >
> > Here is his reference:
> > Title
> > Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due
> > to
> > maternal red-cell alloimmunization. Collaborative Group for Doppler
> > Assessment of the Blood Velocity in Anemic Fetuses [see comments]
> > Author
> > Mari G; Deter RL; Carpenter RL; Rahman F; Zimmerman R; Moise KJ Jr;
> > Dorman
> > KF; Ludomirsky A; Gonzalez R; Gomez R; Oz U; Detti L; Copel JA;
> > Bahado-Singh
> > R; Berry S; Martinez-Poyer J; Blackwell SC
> > Address
> > Department of Obstetrics and Gynecology, Yale University School of
> > Medicine,
> > New Haven, Conn 06520-8063, USA. giancarlo.mari@yale.edu
> > Source
> > N Engl J Med, 342(1):9-14 2000 Jan 6
> > Abstract
> > BACKGROUND: Invasive techniques such as amniocentesis and
> > cordocentesis are
> > used for diagnosis and treatment in fetuses at risk for anemia due to
> > maternal red-cell alloimmunization. The purpose of our study was to
> > determine the value of noninvasive measurements of the velocity of
> > blood
> > flow in the fetal middle cerebral artery for the diagnosis of fetal
> > anemia.
> > METHODS: We measured the hemoglobin concentration in blood obtained
> > by
> > cordocentesis and also the peak velocity of systolic blood flow in
> > the
> > middle cerebral artery in 111 fetuses at risk for anemia due to
> > maternal
> > red-cell alloimmunization. Peak systolic velocity was measured by
> > Doppler
> > velocimetry. To identify the fetuses with anemia, the hemoglobin
> > values of
> > those at risk were compared with the values in 265 normal fetuses.
> > RESULTS:
> > Fetal hemoglobin concentrations increased with increasing
> > gestational age in
> > the 265 normal fetuses. Among the 111 fetuses at risk for anemia, 41
> > fetuses
> > did not have anemia; 35 had mild anemia; 4 had moderate anemia; and
> > 31,
> > including 12 with hydrops, had severe anemia. The sensitivity of an
> > increased peak velocity of systolic blood flow in the middle
> > cerebral artery
> > for the prediction of moderate or severe anemia was 100 percent
> > either in
> > the presence or in the absence of hydrops (95 percent confidence
> > interval,
> > 86 to 100 percent for the 23 fetuses without hydrops), with a false
> > positive
> > rate of 12 percent. CONCLUSIONS: In fetuses without hydrops that are
> > at risk
> > because of maternal red-cell alloimmunization, moderate and severe
> > anemia
> > can be detected noninvasively by Doppler ultrasonography on the
> > basis of an
> > increase in the peak velocity of systolic blood flow in the middle
> > cerebral
> > artery.
> >
> > Regarding the etiology, given the name of the author (and it's Asian
> > origin), I agree that alpha-thalassemia is the most likely
> > diagnosis, as the
> > fetus is unable to make any normal hemoglobin tetrameres of any type:
> > embryonic, fetal or adult.
> >
> > It is quite common in Asian populations:
> > Title
> > Frequency of alpha-thalassemia-1 of the Southeast Asian-type among
> > pregnant
> > women in northern Thailand determined by PCR technique.
> > Author
> > Kitsirisakul B; Steger HF; Sanguansermsri T
> > Address
> > Human Genetics Unit, Faculty of Medicine, Chiang Mai University,
> > Thailand.
> > Source
> > Southeast Asian J Trop Med Public Health, 27(2):362-3 1996 Jun
> > Abstract
> > Five hundred pregnant women were analyzed for the presence of
> > alpha-thalassemia-1 of the Southeast Asian (SEA)-type by polymerase
> > chain
> > reaction (PCR) technique at the Maharaj Nakhon Chiang Mai University
> > Hospital in Chiang Mai during the period from April to June 1995.
> > Forty-four
> > of them (8.8%) were recognized as carriers, corresponding to a
> > frequency of
> > 0.044. Homozygous alpha-thalassemia-1 of the SEA-type, the fatal
> > condition
> > of hemoglobin Bart's hydrops fetalis, has an expected frequency of
> > 0.00194,
> > or about 2 hydrops fetalis cases per 1,000 births in this population.
> >
> > If this is the case, both parents will be microcytic and not
> > necessarily
> > very anemic. If this is the case, the risk for any particular future
> > child
> > to have this problem is 1/4. I believe that DNA testing is available
> > and
> > likely to be informative.
> >
> > Prenatal identification is important because this disease is
> > potentially
> > cureable by a stem cell transplant into the fetus, on an
> > investigational
> > compassionate need basis. Abortion is not really a factor because the
> > disease is universally fatal in its homozygous severe form (the one
> > seen in
> > the fetal hydrops deaths).
> >
> > Theoretically another alternative would be serial intrauterine
> > transfusions
> > like for Rh, and an ultimate curative bone marrow transplant, which
> > is now
> > done for beta thalassemia:
> >
> > Berloni Foundation
> > against thalassemia
> > THE BONE MARROW TRANSPLANTATION CENTER OF PESARO
> > All founds assigned to the Berloni Foundation are directed towards
> > the Bone
> > Marrow Transplantation Center, Pesaro - Haematology Division of the
> > Hospital
> > San Salvatore - which occupies a position of international
> > leadership in the
> > fight of Thalassemia due to the development of the Center's Clinical
> > and
> > Scientific Research programmes.
> > Thalassemia, in its homozigote form, is the most widespreaded genetic
> > disease in the world. In the Mediterranean and Middle East only,
> > there are
> > over 200,000 thalassemic children. In Italy there are 8,000 and
> > 250,000 are
> > born every year. Their survival depens on the possibulity of
> > transfusion
> > from age of 3 to 6 months, every 15 days and receiving subcutaneous
> > injections of desferrioxamine every day - continuosly - for serious
> > anaemia
> > and to remove part of the iron contained in the trasfusions. During
> > the
> > first 10 years the mortality rate in 5%, in the next ten years
> > between 5%
> > and 10% and after the age of twenty it reaches 50%.
> >
> > Up until december 1981 thalassemic children and their families were
> > left
> > completely in the dark when it came the possibility of a cure. Since
> > then,
> > however, against all odds, criticism and biological barriers
> > considered
> > insurmountable, the Bone Marrow Transplantation Center, after
> > surviving the
> > initial mortalities has performed hundreds and hundreds transplants,
> > 65% of
> > them in thalassemic children. Today the 80% of those children are at
> > home
> > cured of the disease.
> >
> > Apart from childrem Sardinia, Sicily, Calabria, Lombardia, Piemonte
> > and alla
> > other regions in Italy, transplants have been performed on children
> > from
> > Iran, India, Palestine, Arab Countries and many other nations
> > including USA,
> > Russia, Romania, Argentina, South Africa, Tobago. Due to the
> > requests for
> > transplants arriving from all over the world the current waiting
> > list at the
> > Bone Marrow Transplantation Center of Pesaro has reached 14 months.
> >
> > The impact of this discovery in Italy on the international scientific
> > community has been of enormous proportions, but still more important
> > has
> > been the light of hope instilled in hearts of the families with
> > thalassemic
> > children.
> > All results obtained at the Bone Marrow Transplantation Center are
> > passed on
> > to University Clinics an Italian and foreign Hospitals who are
> > committed to
> > curing Thalassemia by way of transplant protocol which is today
> > known as
> > "The Pesaro Protocol". Due to the increase od doctors' request for
> > clinical-scientific training at the Pesaro Center, exchanges on an
> > international basis are expected. To this end, scientific and
> > didactic
> > collaboration programmes have been established, in according whit the
> > Ministery of foreign Countries, with various countries including
> > Iran,
> > Russia, Romania and India. It is the hope that one day, in these
> > countries,
> > autonomous Bone Marrow Transplantation Centers will be in operation,
> > like
> > the one already realized at Minsk in Belarousse with the finances of
> > the
> > Berloni Foundation.
> >
> > Prof. Guido Lucarelli
> > Scientific Programme Chief
> > Bone Marrow Transplantation Center
> > Chief Physician
> > Haematology Department
> > San Salvatore Hospital, Pesaro
> >
> > The following from OMIM may be helpful:
> >
> > http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?141800
> >
> > TEXT
> > The alpha and beta loci determine the structure of the 2 types of
> > polypeptide chains in the tetrameric adult hemoglobin, Hb A,
> > alpha-2/beta-2.
> > The alpha locus also determines a polypeptide chain, the alpha
> > chain, in
> > fetal hemoglobin (alpha-2/gamma-2), in hemoglobin
> > A2(alpha-2/delta-2), and
> > in embryonic hemoglobin (alpha-2/epsilon-2). The number of normal
> > alpha
> > genes (3, 2, 1 or none) in Asian cases of alpha-thalassemia results
> > in 4
> > different alpha-thalassemia syndromes (Kan et al., 1976). Three
> > normal alpha
> > genes gives a silent carrier state. Two normal alpha genes results in
> > microcytosis (so-called heterozygous alpha-thalassemia). One normal
> > alpha
> > gene results in microcytosis and hemolysis (so-called Hb H disease).
> > No
> > normal alpha gene results in 'homozygous alpha-thalassemia'
> > manifested as
> > fatal hydrops fetalis.
> > By studies of somatic cell hybrids, Deisseroth et al. (1976) showed
> > that the
> > alpha and beta loci are on different chromosomes. Gandini et al.
> > (1977)
> > concluded, incorrectly as it turned out, that the alpha loci are on
> > the long
> > arm of chromosome 4 (4q28-q34). The conclusion was based on a
> > finding of
> > excessive synthesis of alpha chains in patients with duplication of
> > this
> > region. Deisseroth et al. (1977) combined the methods of somatic cell
> > hybridization and DNA-cDNA hybridization to establish assignment of
> > the
> > alpha-globin locus to chromosome 16. This represents an extension of
> > the
> > cell hybridization method permitting mapping of genes that are not
> > functional in the cultured cell. Weitkamp et al. (1977) presented
> > data
> > concerning linkage of the alpha and beta loci to 34 marker loci.
> > Data on
> > alpha-thalassemia, combined with those on the Hopkins-2 variant,
> > excluded
> > linkage of alpha and haptoglobin at a recombination fraction less
> > than 0.15.
> > Deisseroth and Hendrick (1978) confirmed the assignment of the alpha
> > locus
> > to chromosome 16 by means of cotransfer of this gene with the human
> > APRT
> > gene, known to be on 16 (see 102600), into mouse erythroleukemia
> > cells. (The
> > APRT gene is on the long arm of chromosome 16.) On the basis of
> > findings in
> > a case of partial trisomy 16, Wainscoat et al. (1981) concluded that
> > the
> > alpha-globin genes are on segment 16p12-pter. By combining somatic
> > cell
> > hybridization with a cDNA probe in the study of a cell line with
> > reciprocal
> > translocation between 16q and 11q, Koeffler et al. (1981) showed
> > that the
> > alpha-globin genes are on the short arm of 16. Gerhard et al. (1981)
> > used an
> > improved method of in situ hybridization to confirm the assignment
> > of the
> > alpha-globin cluster to chromosome 16p. The evidence on the precise
> > location
>
> > > fetal infection and karyotype), you should screen both parents for
> > alpha
> > > (in particular but also beta)-thalassemia (because some fetuses
> > from Asia
> > > may have both disorder) in view of previous obstetric history and
> > patient
> > > from Taiwan.
> > >
> > > *****************************************************************
> > > The-Hung Bui, M.D.
> > > Senior Consultant
> > > Director, Fetal Diagnosis Programme
> > > Department of Molecular Medicine
> > > Clinical Genetics Unit
> > > Karolinska Hospital
> > > S-171 76 Stockholm, Sweden
> > >
> > > phone: +46 8 517 74989 or 517 72472 (secretary)
> > > fax: +46 8 32 77 34
> > > E-mail: The-Hung.Bui@ks.se
> > > ******************************************************************
> > >
> >
>
