Osteogenesis Imperfecta Type II with Patent Ductus Arteriosus, Severe Persistent Pulmonary Hypertension, Sepsis and Severe Thrombocytopenia in A Neonate: A Case Report.

Abstract

Background: Osteogenesis imperfecta type II is a rare congenital anomaly that usually causes death in utero or shortly after birth.
Case Presentation: This study reports a rare case of osteogenesis imperfecta type II in an Afghan girl who was one day old. The defect was accompanied by a patent ductus arteriosus, severe persistent pulmonary hypertension of the newborn, sepsis, severe thrombocytopenia, and low birth weight during the first four days of life. These disorders were diagnosed by medical history, physical examination, blood investigation, computed tomography, x-ray, and doppler ultrasonography. On the fifth day of life, the newborn suffered an abrupt cardio-pulmonary arrest that resulted in her death, presumably due to brainstem compression or severe persistent pulmonary
hypertension of the newborn.
Conclusion: Osteogenesis imperfecta type II can result in life-threatening complications during the first week of
life.

Full text

Global Pediatrics 9 (2024) 100203
Available online 5 July 2024
2667-0097/© 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
Osteogenesis imperfecta type II with patent ductus arteriosus, severe
persistent pulmonary hypertension, sepsis and severe thrombocytopenia in
a neonate: A case report
Mansoor Aslamzai
a
,
*
, Mohammad Sharif Sediqi
b
, Mohmand Mangal
b
, Ataullah Shinwarie
c
a
Professor, Department of Neonatology, Kabul University of Medical Sciences, 3rd district, 1003, Kabul, Afghanistan
b
Assistant Professor, Department of Pediatrics, Kabul University of Medical Sciences, 3rd district, 1003, Kabul, Afghanistan
c
Family Physician, Doctors at Underwood Medical Centre, Australia
ARTICLE INFO
Keywords:
Osteogenesis imperfecta
Congenital heart disease
Infection and Newborn
ABSTRACT
Background: Osteogenesis imperfecta type II is a rare congenital anomaly that usually causes death in utero or
shortly after birth.
Case Presentation: This study reports a rare case of osteogenesis imperfecta type II in an Afghan girl who was one
day old. The defect was accompanied by a patent ductus arteriosus, severe persistent pulmonary hypertension of
the newborn, sepsis, severe thrombocytopenia, and low birth weight during the rst four days of life. These
disorders were diagnosed by medical history, physical examination, blood investigation, computed tomography,
x-ray, and doppler ultrasonography. On the fth day of life, the newborn suffered an abrupt cardio-pulmonary
arrest that resulted in her death, presumably due to brainstem compression or severe persistent pulmonary
hypertension of the newborn.
Conclusion: Osteogenesis imperfecta type II can result in life-threatening complications during the rst week of
life.
1. Background
Osteogenesis imperfecta (OI) is a rare congenital and genetic con-
nective tissue disorder with a prevalence of one in 20,000–50,000 in-
dividuals.
1-5
OI mostly affects bone, but it also impacts other tissues that
contain a lot of type I collagen, including joints, eyes, ears, skin, and
teeth.
4
Skeletal fragility in OI predisposes patients to multiple fractures,
including the ribs.
1
According to Sillence and Rimoin, the clinical
severity of the OI can be classied as perinatally fatal (type II), severe
(type III), moderate (type IV), and mild (type I).
2
The diagnosis of OI
usually takes place clinically, with radiographic support.
1
Treatment of
Osteogenesis Imperfecta focuses on preventing fractures and correcting
bone deformities.
2
Most cases of OI lead to signicant physical disabil-
ities. Eighty percent of individuals with type II OI die during the rst
week of life, and survival beyond 1 year is very rare. Some cases of type
I, or mild form, live normally.
6
We reported this case because of a
scarcity of information in the current literature about osteogenesis
imperfecta type II accompanied by a patent ductus arteriosus, severe
persistent pulmonary hypertension of the newborn, sepsis, severe
thrombocytopenia, and low birth weight in a newborn baby.
2. Case report
A one-day-old Afghan newborn girl was admitted to the Neonatal
Unit of a Teaching Hospital due to poor feeding, respiratory distress, and
cyanosis at 12 h of birth. She was born by normal vaginal delivery at 38
weeks of gestation with a birth weight of 2 kg to a 29-year-old multi-
gravida mother at a tertiary hospital. The mother took only routine
medications and was in good health throughout her pregnancy. The
rst-trimester prenatal ultrasonography detected no fractures or other
abnormalities. There was no family history of a tendency to fractures,
nor had the infant experienced any trauma or surgery. Additionally,
there was no family history of any newborns with fractures at birth. In
terms of consanguinity, the parents were third-degree relatives. On
general physical examination, a frog-like position, bluish sclera, leth-
argy, an axillary temperature of 36.8ºC, a heart rate of 148/min, a res-
piratory rate of 72/min, a length of 37 cm, a head circumference of 35
cm, sluggish primitive reexes, and an oxygen saturation of 72 % were
* Corresponding author at: Professor at the Department of Neonatology, KUMS,1003, 3rd district, Kabul, Afghanistan.
E-mail address: mansooraslamzai@gmail.com (M. Aslamzai).
Contents lists available at ScienceDirect
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journal homepage: www.elsevier.com/locate/gpeds
https://doi.org/10.1016/j.gpeds.2024.100203
Received 4 December 2023; Accepted 25 June 2024

Global Pediatrics 9 (2024) 100203
2
detected. On local physical examination, softening of the skull, curved
lower limbs, and multiple skeletal deformities with skin folds on all
extremities were observed (Fig. 1). An analysis of the blood showed a
hemoglobin of 16 g/dl, a white blood cell count of 21,000/mm
3
(neutrophil 54.6 %, lymphocytes 36 %, eosinophils 4 %, monocytes 4.4
% and basophils 1 %), a red blood cell count of 4.9 million/ mm
3
(mean
corpuscular hemoglobin of 34 pg, mean corpuscular volume of 99.5 ), a
thrombocyte count of 37,000/mm
3
, a reticulocyte count of 2 %, a C-
reactive protein of 12 mg/dl and a blood sugar of 89 mg/dl. Arterial
blood gas analysis showed pH (7.36), pCO
2
(30 mmHg), pO
2
(60
mmHg), and bicarbonate (20meq/L). Neonatal sepsis and severe
thrombocytopenia were diagnosed based on abnormal clinical and
laboratory ndings, such as lethargy, sluggish primitive reexes, fast
breathing, leukocytosis, an elevated level of C-reactive protein, and a
low platelet count. The patient received 20 ml of platelet transfusion
over 30 min and was put on intravenous glucose 10 % as maintenance
uid, oxygen, and antibiotics consisting Cefotaxime and Ampicillin
intravenously during the rst and second days of life. In addition to the
mentioned management, we started giving expressed breast milk
through a nasogastric tube and, began to the add sodium and potassium
to the intravenous uid on the third day. Demineralization and multiple
deformities with fractures of all long bones and ribs were visible on the
x-ray of the chest and extremities (Fig. 2). On the fourth day of life, the
doppler echocardiography revealed a 3 mm patent ductus arteriosus
(PDA) (Fig. 3) and severe persistent pulmonary hypertension of the
newborn (PPHN) with a pressure of 69 mmHg (Fig. 4), as well as
computed tomography (CT) of the head showed low-density and insuf-
cient skull bones. There was no evidence of intraventricular hemor-
rhage (Fig. 5). Ultimately, osteogenesis imperfecta type II with patent
ductus arteriosus, severe PPHN, sepsis, severe thrombocytopenia, and
low birth weight (LBW) was the nal diagnosis. Therefore, diuretic
therapy, restriction of maintenance uid, and three doses of oral
ibuprofen were recommended as medical care for PDA. Respiratory
support and Sildenal were used to treat severe PPHN, together with the
management of neonatal sepsis and severe thrombocytopenia. Inhaled
nitric oxide (iNO), the most effective pulmonary vasodilator, is not
available in our country. A sudden cardio-pulmonary arrest occurred on
the fth day of life, possibly as a result of brainstem compression or
severe persistent pulmonary hypertension of the newborn. The infant
died despite advanced cardiopulmonary resuscitation.
3. Discussion
Osteogenesis imperfecta, or brittle bone disease, is a rare inherited
disorder of connective tissue with the common feature of excessive
fragility of bones.
4
The Latin term osteogenesis imperfecta, which means
imperfect bone formation, was used in the 1840s by Willem Vrolik to
denote a newborn with many fractures.
2
Autosomal dominant inheri-
tance is the most common form of the OI, while recessive and X-chro-
mosome-linked variants are rarely discovered.
4
According to its
severity, OI is clinically categorized into four types (I-IV).
1
Type I, the
mildest phenotype, accounts for 71 % of cases, whereas type II, the most
severe phenotype, accounts for 12 % of cases. Clinical signs include
recurrent fractures, bowing of the long bones, blue sclera, stunted
growth, generalized low bone mass, and ligamentous and joint laxity.
1,2
Fig. 1. Softening of the skull, curved lower limbs, and multiple skeletal deformities with skin folds on all extremities were observed.
Fig. 2. The x-ray of the chest and extremities shows demineralization and
multiple deformities along with fractures of all long bones and ribs on the rst
day of life which are diagnostic ndings of OI type I in the index neonate.
M. Aslamzai et al.

Global Pediatrics 9 (2024) 100203
3
Congenital heart disease (CHD) and heart problems may be associated
with OI.
4
Clinical feature and radiographic ndings are usually used to
make a diagnosis of OI.
1
These patients are more susceptible to the in-
fections of the respiratory tracts. The most serious form of OI, type II,
causes death in utero or shortly after birth.
1
In this type, fetal and
neonatal deaths are mainly due to respiratory failure, basilar invagina-
tion, brain stem compression, and intracranial hemorrhage.
6-8
Patients
with type I, or mild form, sometime live normally. A vessel known as the
ductus arteriosus (DA) connects the descending aorta to the pulmonary
artery. In term newborns, a patent ductus arteriosus (PDA) is an open DA
following the rst three days of life.
9,10
Since PDA has a negative impact
on respiratory outcomes, its closure improves lung function. Diuretic
therapy, restriction of maintenance uid, and three doses of oral
ibuprofen provide the medical management of PDA.
9,11
PPHN is dened as consistently high pulmonary vascular resistance
in the newborn. This causes blood to shunt from right to left through the
foramen oval and ductus arteriosus.
12
PPHN frequently manifests early
after birth, causing signicant respiratory distress and hypoxia. Echo-
cardiography is one of the most efcient diagnostic techniques.
13
The
management of PPHN includes respiratory support and using pulmonary
vasodilators in order to minimize pulmonary vascular resistance and
reduce the magnitude of the right-to-left shunt.
12
A systemic inammatory response syndrome due to a conrmed or
suspected infection describes as neonatal sepsis. The diagnostic mani-
festations include a uctuating body temperature, tachycardia,
tachypnea, chest retraction, leukopenia or leukocytosis, cyanosis, hyp-
oxia, and an increased C-reactive protein. The cornerstones of man-
agement are antibiotic therapy and supportive care.
14,15
Low-birth-weight (LBW) newborns are referred to those weighing be-
tween 1500 and 2500 g at birth.
14
According to the clinical and imaging ndings, the present baby had
Fig. 3. The doppler echocardiography demonstrates a 3 mm patent ductus arteriosus (PDA).
Fig. 4. The doppler echocardiography shows a severe persistent pulmonary
hypertension of the newborn (PPHN) with a pressure of 69 mmHg.
Fig. 5. The computed tomography (CT) of the head shows low-density and
insufcient skull bones in the index baby. There is no evidence of intraven-
tricular hemorrhage.
M. Aslamzai et al.

Global Pediatrics 9 (2024) 100203
4
OI type II. Clinical diagnostic ndings of OI type II were frog-position,
short stature, softening of the skull, blue sclera, curved lower limbs,
and multiple skeletal deformities with skin folds on all four extremities
of the infant that were observed at birth (Figs. 1 and 2). Demineraliza-
tion and multiple deformities with fractures of all long bones and ribs
were visible on the x-ray of the chest and extremities [Fig. 3]. The head
CT scan showed low-density and insufcient skull bones [Figure 7]. The
parental consanguinity, suggesting a possible role of genetics, was pos-
itive in the current case. The clinical and radiographic features, the
normal rst trimester ultrasonography and possible role of genetics are
similar to those in the literature.
1,5,16,17
Osteopenia of prematurity and
achondroplasia may be considered in the differential diagnosis of OI.
Osteopenia of prematurity typically presents between weeks 5 and 11
after birth in extremely preterm and very low birth weight.
1
In contrast
to OI, infants with achondroplasia suffer short limbs, hands and ngers,
frontal bossing, a depressed nasal bridge, and a large head in the absence
of multiple skeletal deformities and fractures.
18
The baby in our case
was died on the fth day of life due to cardiopulmonary arrest, pre-
sumably caused by brain stem compression or severe persistent pul-
monary hypertension. Such a poor prognosis for OI type II was observed
in many studies.
6-8,16
The doppler echocardiography of the baby revealed a 3 mm patent
ductus arteriosus (PDA) and severe persistent pulmonary hypertension
of the newborn with a pressure of 69 mmHg [Figs. 4-6]. Neonatal sepsis,
severe thrombocytopenia, and LBW were diagnosed on the basis of
abnormal clinical and laboratory ndings, including leukocytosis, an
elevated level of C-reactive protein, a low thrombocyte count, and a
birth weight of 2 kg. The current case was accompanied by PDA,
neonatal sepsis and LBW, suggesting a possible predisposing role of OI in
the pathogenesis of CHD, infection and LBW. This hypothesis is consis-
tent with the ndings of the two studies.
1,4
A notable distinction from
earlier reported cases is highlighted in our case by the presence of PDA,
severe PPHN, sepsis, severe thrombocytopenia and LBW with OI type
II.
1,3,4,16,17
4. Conclusion
OI type II is a lethal and rare type of brittle bone disease that may
complicate critical events, including severe PPHN, brain stem
compression, and death during the rst week of life. Since the current
case was accompanied by PDA, neonatal sepsis and LBW, OI may be an
associated factor of CHD, infection, and LBW. It will be better to eval-
uate the mentioned issues by analytical studies.
CRediT authorship contribution statement
Mansoor Aslamzai: Conceptualization, Data curation, Investiga-
tion, Methodology, Writing – original draft, Writing – review & editing.
Mohammad Sharif Sediqi: Data curation. Mohmand Mangal: Data
curation. Ataullah Shinwarie: Writing – review & editing.
Declaration of competing interest
The authors declare that they have no known competing nancial
interests or personal relationships that could have appeared to inuence
the work reported in this paper.
Acknowledgements
We would like to thank the personnel of the Neonatal Unit at Mai-
wand Teaching Hospital for their assistance with this study, especially
Dr. Abdul Basir Abdurrhimzai.
Ethics approval and consent to participate
This case report was approved by the Department of Neonatology
(Protocol No. 4, dated 17/6/2023), Kabul University of Medical
Sciences.
Consent for publication
The mother of the baby gave her written informed agreement for the
publication of this case report and the accompanying images. The Hel-
sinki Declaration was taken into consideration. A copy of the written
consent is available for review by the Editor-in-Chief of this journal.
Availability of data and materials
The documents used during the current study are available from the
corresponding author on reasonable request.
Funding
The authors received no specic grant from any funding agency in
the public, commercial, or not-for-prot sectors.
Authors’ contributions
MA evaluated the baby’s clinical features, x-ray, CT scan and doppler
ultrasonography in order to reach a denitive diagnosis, as well as
provided the manuscript. MSS and MM collected the data. AS reviewed
the manuscript. All authors read and approved the nal manuscript.
Authors’ information
Mansoor Aslamzai is a professor at the Department of Neonatology,
Kabul University of Medical Sciences, Afghanistan. He became a mem-
ber of the European Society for Pediatric Research in 2021. Mohammad
Sharif Sediqi and Mohmand Mangal are assistant professors at the
Department of Pediatrics, KUMS. Ataullah Shinwarie is Family Physi-
cian, at the Doctors Underwood Medical Centre, Australia.
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