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Case Repo s in Obs e ics and Gynecology
Volume 2013, A icle ID 472356, 4 pages
h p://dx.doi.o g/10.1155/2013/472356
Case Repo
Hype ophic Ca diomyopa hy due o Mi ochond ial Disease:
P ena al Diagnosis, Managemen , and Ou come
Lu ga do Ga cía-Díaz,
1
Félix Cose ia,
2
and Guille mo An iñolo
1, 3
1
Unidad de Ges ión Clínica de Gené ica, Rep oducción y Medicina Fe al, Ins i u o de Biomedicina de Se illa (IBIS),
Hospi al Uni e si a io Vi gen del Rocío, CSIC, Uni e sidad de Se illa, 41013 Se illa, Spain
2
Unidad de Ges ión Clínica de Pedia ía, Sección de Ca diología In an il, Hospi al In an il, Hospi al Uni e si a io Vi gen del Rocío,
41013 Se illa, Spain
3
Cen o de In es igación Biomédica en Red de En e medades Ra as (CIBERER), Hospi al Uni e si a io Vi gen del Rocío,
A enida Manuel Siu o s/n, 41013 Se illa, Spain
Co espondence should be add essed o Guille mo An iñolo; guille mo.an inolo.sspa@jun adeandalucia.es
Recei ed 6 No embe 2012; Accep ed 3 Decembe 2012
Academic Edi o s: C. S. Hsu and L. Sen ilhes
Copy igh © 2013 Lu ga do Ga cía-Díaz e al. is is an open access a icle dis ibu ed unde he C ea i e Commons A ibu ion
License, which pe mi s un es ic ed use, dis ibu ion, and ep oduc ion in any medium, p o ided he o iginal wo k is p ope ly
ci ed.
A case o p ena ally diagnosed e al hype ophic ca diomyopa hy is epo ed. e mo he was e e ed o ou depa men a
37 weeks’ ges a ion because o suspec ed congeni al hea disease. P ena al echoca diog aphy showed bi en icula hype ophy
and pe ica dial effusion, wi hou addi ional abno mali ies. Pos na al echoca diog aphy con� med p ena al diagnosis. Neona al
EKG showed bi en icula hype ophy and Wolff-Pa kinson-Whi e synd ome. Skele al muscle biopsy was consis en wi h
mi ochond ial oxida i e phospho yla ion de ec in ol ing a combined de ec o espi a o y complexes I and IV. Echoca diog aphic
ollowup du ing he � s yea o li e showed p og essi e eg ession o hype ophy and e olu ion o le en icula myoca dial
noncompac ion.
1. In oduc ion
Ca diomyopa hies a e among he clinical p esen a ions
associa ed wi h mi ochond ial oxida i e phospho yla ion
de ec s [1]. Ca diomyopa hies a e a signi�can clinical p ob-
lem associa ed wi h sudden dea h, which can be isola ed
o associa ed o o he ca diac and nonca diac condi ions
[1].
Neona al mi ochond ial ca diomyopa hies a e oen
cha ac e ized by hype ophy o one, gene ally le, o bo h
en icles. Ven icula dys unc ion may be p og essi e in-
u e o and ae bi h. Neona al ca diomyopa hy oen lead
o a al hea ailu e, al hough may e en ually p og ess in o
a dila ed o m [2], in o noncompac ion o le en icle,
imp o e o e en eg ess comple ely [3].
We p esen he case o a e us diagnosed wi h hype -
ophic ca diomyopa hy a 37 weeks’ ges a ion, which was
�nally ound o ha e a mi ochond ial oxida i e phospho y-
la ion de ec .
2. Case Repo
A 30-yea -old woman, g a ida 3, was e e ed o ou
Depa men a 37 weeks’ ges a ion due o an abno mal
obs e ic ul asound. Pe sonal and p egnancy his o y we e
un ema kable. Familial his o y e ealed a p e ious child
died because o congeni al ca diac anomaly, namely double
ou le igh en icle. Fe al echoca diog aphic e alua ion
showed bi en icula hype ophy and pe ica dial effusion
(see Figu e 1), and le en icula ejec ion ac ion was 55%.
e e us showed no o he sign o ca diac ailu e o addi ional
hea abno mali ies. Fe al ul asound examina ion e ealed
an o he wise heal hy male e us. A 38 weeks’ ges a ion, a
2,836 g male was bo n by elec i e caesa ean sec ion. Apga
sco e was 10 a 1 minu e and 10 a 5 minu es. e neona al
echoca diog am con� med e al diagnosis (see Figu e 2) and
le en icula ejec ion ac ion was 52%. Elec oca diog am
(EKG) showed bi en icula hype ophy wi h p eexci a ion,
which was consis en wi h Wolff-Pa kinson-Whi e synd ome
2 Case Repo s in Obs e ics and Gynecology
F 1: Fe al echoca diog aphy a 37 weeks shows ca diac hype ophic in ol ing he igh en icula , le en icula and in e en icula
sep um, and pe ica dial effusion.
(a) (b)
(c) (d)
F 2: Neona al echoca diog aphy showing ca diac mo phology simila o ha in e al echoca diog aphy.
(see Figu e 3). Ches X- ay showed mode a e ca diomegaly.
T ea men was s a ed wi h diu e ics and digoxin and
he pa ien emained s able, wi hou ca diac symp oms o
a hy hmia.
Skele al muscle his opa hological and spec opho ome -
ic s udies we e diagnos ic o a mi ochond ial oxida i e
phospho yla ion de ec in ol ing espi a o y complexes I
and I V.
Follow-up echoca diog aphy showed p og essi e eg es-
sion o hype ophy, excep a le pos e io wall and in e -
en icula sep um, wi h no changes in en icula unc ion
and no pe ica dial effusion. A he same ime, le en ic-
ula myoca dium de eloped abecula ions accomplishing
le en icula noncompac ion c i e ia. Pa en s echoca dio-
g aphic s udy was no mal. In addi ion, he pa ien p esen s
a no mal psychomo o de elopmen . Cu en ly he pa ien
Case Repo s in Obs e ics and Gynecology 3
(a) (b)
F 3: Neona al elec oca diog am showing bi en icula hype ophy.
has h ee yea s old and is ea ed wi h enalap il and i amin
complex.
3. Discussion
Ca diomyopa hies a e a e y a e disease in e uses wi h a
e y poo ou come. Only isola ed case epo s and small case
se ies we e epo ed. In se ies o neona es and in an s he CM
occu in abou 2–7%, bu p obably du ing he e al li e he
p e alence is highe : 6%–11%[4].
Neona al ca diomyopa hies due o mi ochond ial oxida-
i e phospho yla ion de ec s a e se e e condi ions which can
beei he isola edo pa o amul io gandiseasein ol ing
b ain, skele al muscle, li e , and kidney, in addi ion o hea
[5].
Incidence o neona al mi ochond ial ca diomyopa hies
can only be app oached using he epo s o e e al diagnos-
ic cen e s. Gibson e al., in a se ies o 32 newbo ns, epo ed
29%o mi ochond ialdiseaseswi haneona alonse [6].
Ga cía-Cazo la e al., in a se ies o 57 newbo ns, epo a
much lowe p opo ion, 5,2%[7].
Ca diomyopa hy is mo e oen hype ophic han dila ed.
Howe e , i may e en ually p og ess in o a dila ed o m o
le en icula noncompac ion ca diomyopa hy. An ena al
mani es a ions such as e al hype ophic ca diomyopa hy,
a hy hmia, and/o hyd ops ha e been epo ed [2]. In
ex emely se e e cases, neona al ca diogenic shock may
occu [2].
Ca diomyopa hy pa hophysiological mechanisms a e
complex, and neona al myoca dium equi es a no mal mi o-
chond ial unc ioning o i s me abolic shi om p ena al
anae obic glycolysis o pos na al me abolism, elying on
a y acid oxida ion, ke one body ca abolism, and oxida i e
phospho yla ion [8]. Complex I de�ciency is ega ded as
he mos common de ec associa ed wi h ca diomyopa hy
[9]. Complex I is he � s , la ges , and mos complica ed
espi a o y complex in mi ochond ia. Al e a ions a his le el
can cause mal unc ion o a mi ochond ial a ge ing signal
and e en ually lead o human diseases. In an s and child en
ca ying complex I de�ciency can de elop p ima y lac ic
acidosis, which may lead o se e e mic ocephaly and ce eb al
a ophy and is associa ed wi h ea ly-onse hype ophic ca -
diomyopa hy and encephalopa hy [1]. Biopsies om skele al
muscle, li e o hea can be pe o med in o de o con� m
he disease [10].
In neona al ca diomyopa hy, EKG moni o ing is neces-
sa y o ea ly de ec ion o en icula a hy hmias, which a e
some imes p ecu so s o episodes o sudden dea h [2]. In en-
si e ca e is oen equi ed o hese se e e diseases o su i e
he neona al pe iod, as many pa ien s need en ila o y and
ci cula o y suppo [2].
Mi ochond ial ca diomyopa hies a e mo e se e e han
mi ochond ial diseases wi hou hea in ol emen , being
he su i al a e a 16 yea s o age o ca diomyopa hic
pa ien s 18% e sus 95%su i al a he same age in non-
ca diomyopa hic pa ien s [11].
Al hough hea dys unc ion may be no p og essi e o
e en eg ess ae wa ds, neona al mi ochond ial ca diomy-
opa hies oen ha e a apidly a al ou come. P ena al diag-
nosis and e al echoca diog aphy may imp o e pe ina al
ca e based on he expec ed na u al his o y and pos na al
cou se. In addi ion, de ailed e alua ion o e al and ma e nal
condi ion and s anda dized diagnos ic p ocedu es p o ide
p ognos ic in o ma ion o gene ic counseling and u he
po en ial p ena al diagnosis.
Re e ences
[1] P. Béni , R. Beugno , D. Ch e ien e al., “Mu an NDUFV2 sub-
uni o mi ochond ial complex I causes ea ly onse hype ophic
ca diomyopa hy and encephalopa hy,” Human Mu a ion, ol.
21, no. 6, pp. 582–586, 2003.
4 Case Repo s in Obs e ics and Gynecology
[2] D. Le , A. Nissenko n, E. Leshinsky-Sil e e al., “Clinical
p esen a ions o mi ochond ial ca diomyopa hies,” Pedia ic
Ca diology, ol. 25, no. 5, pp. 443–450, 2004.
[3] J. Fins e e , “Ca diogene ics, neu ogene ics, and pa hogene ics
o le en icula hype abecula ion/noncompac ion,” Pedi-
a ic Ca diology, ol. 30, no. 5, pp. 659–681, 2009.
[4] M. Mongio ì, V. Fesslo a, G. Fazio, G. Ba ba o, and S. Pipi one,
“Diagnosis and p ognosis o e al ca diomyopa hies: a e iew,”
Cu en Pha maceu ical Design, ol. 16, no. 26, pp. 2929–2934,
2010.
[5] M. Schiff, H. Ogie de Baulny, and A. Lombès, “Neona al
ca diomyopa hies and me abolic c ises due o oxida i e phos-
pho yla ion de ec s,” Semina s in Fe al and Neona al Medicine,
ol. 16, no. 4, pp. 216–221, 2011.
[6] K. Gibson, J. L. Halliday, D. M. Ki by, J. Yapli o-Lee, D. R. o -
bu n, and A. Boneh, “Mi ochond ial oxida i e phospho yla ion
diso de s p esen ing in neona es: clinical mani es a ions and
enzyma ic and molecula diagnoses,” Pedia ics, ol. 122, no. 5,
pp. 1003–1008, 2008.
[7] A. Ga cía-Cazo la, P. De Lonlay, M. C. Nassogne, P. Rus in, G.
Toua i, and J. M. Saudub ay, “Long- e m ollow-up o neona al
mi ochond ial cy opa hies: a s udy o 57 pa ien s,” Pedia ics,
ol. 116, no. 5, pp. 1170–1177, 2005.
[8] J. C. Von Kleis -Re zow, V. Co mie -Dai e, G. Vio e al.,
“An ena almani es a ions o mi ochond ial espi a o y chain
de�ciency,” Jou nal o Pedia ics, ol. 143, no. 2, pp. 208–212,
2003.
[9] J. Yapli o-Lee, R. Wein aub, K. Jamsen, C. W. Chow, D. R.
o bu n, and A. Boneh, “Ca diac mani es a ions in oxida i e
phospho yla ion diso de s o childhood,” Jou nal o Pedia ics,
ol. 150, no. 4, pp. 407–411, 2007.
[10] P. Rus in, J. Lebidois, D. Ch e ien e al., “Endomyoca dial
biopsies o ea ly de ec ion o mi ochond ial diso de s in
hype ophic ca diomyopa hies,” Jou nal o Pedia ics, ol. 124,
no. 2, pp. 224–228, 1994.
[11] F. Scaglia, J. A. Towbin, W. J. C aigen e al., “Clinical spec um,
mo bidi y, and mo ali y in 113 pedia ic pa ien s wi h mi o-
chond ial disease,” Pedia ics, ol. 114, no. 4, pp. 925–931, 2004.
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