International Journal of Contemporary Pediatrics

Venkat CG et al. Int J Contemp Pediatr. 2021 Jun;8(6):1102-1106

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DOI: https://dx.doi.org/10.18203/2349-3291.ijcp20212056
Case Series

Thiamine responsive pulmonary hypertension: case series

Cuddapah Gaurav Venkat1, Vallivedu Chennakesavulu Pujitha1*,
Kanchan S. Channawar2, Vadde Vasavi3

1
Kamineni Academy of Medical Sciences and Research Centre Hyderabad, Telangana, India
2
Critical care medicine, Kamineni Academy of Medical Sciences and Research Centre Hyderabad, Telangana, India
3
Kamineni Academy of Medical Sciences and Research Centre Hyderabad, Telangana, India

Received: 22 March 2021

Accepted: 30 April 2021

*Correspondence:
Dr. Vallivedu Chennakesavulu Pujitha,
E-mail: [email protected]

Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Pulmonary hypertension (PH) is most commonly related either to a cardiac or a pulmonary cause. But less commonly
various hematological, hepatic, genetic causes are also associated. Infantile PH due to vitamin deficiencies is very rare
though few cases with thiamine deficiencies causing PH have been reported lately. Lack of awareness and late
recognition of thiamine deficiency may result in high mortality. A high index of suspicion is required for early
diagnosis and management to decrease the severity and morbidity and thereby preventing long term implications on
neurological development. Here, we described three cases of infants admitted to Kamineni academy of medical
sciences diagnosed with PH who responded dramatically to thiamine supplements. The lack of rapid diagnostic
capacity and the severe outcome of thiamine deficiency justify the use of a therapeutic thiamine challenge in cases
with high clinical suspicion. Increased awareness about thiamine deficiency and low threshold for thiamine use
should guide clinicians in their practice.

Keywords: Thiamine, Pulmonary hypertension, 2D ECHO, Cardiomegaly

INTRODUCTION chain alpha ketoacid dehydrogenase (MSUD);

erythrocyte transketolase.
Infantile PH due to vitamin deficiencies is very rare
though few cases with thiamine deficiencies causing PH Deficiency can also cause dry and wet beri beri. Wet beri
have been reported lately. Thiamine being an essential beri can cause congestive heart failure most commonly
water soluble B1 vitamin needs to be supplied right heart failure, which can lead to decrease in
exogenously with limited body stores and high turnover circulatory volume, lactic acidosis, but lately PH in
rate.1,2 Thiamine diphosphate (TDP) is the predominant thiamine deficiency cases were reported in India.3
intracellular metabolite. TDP levels provide a better
measure of body thiamine status but do not assess Lack of awareness and late recognition of thiamine
thiamine metabolic function. Erythrocyte transketolase deficiency may result in high mortality. A high index of
activity (ETKA) is more accurate in assessing the suspicion is required for early diagnosis and management
functional thiamine status of the body. Thiamine is a co to decrease the severity and morbidity and thereby
factor in many enzymatic processes like pyruvate to preventing long term implications on neurological
acetyl CoA by pyruvate dehydrogenase (lactic acidosis) ; development.3
alpha ketoglutarate to succinyl CoA by alpha
ketoglutarate dehydrogenase (krebs cycle); branched

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CASE SERIES Case 2

Case 1 A 5 month old baby was brought to EMD with

complaints of cold and cough, increase work of
A 2 month old male baby presented to the EMD with breathing, decrease of feeds and lose stools since 3 days,
complaints of cold and cough since 7 days, increased shortness of breath since 1 day. No similar complaints in
work of breathing, decrease in urine output since 4 days, the past. No significant family history.
decrease intake of feeds since 3 days and fever since 1
day associated with vomiting. Baby had similar
complains 3 weeks ago for which the baby was
hospitalized and supportive care was given. Baby had
similar history of respiratory infections since birth. No
significant family history or any chronic respiratory
illnesses.

Antenatal history

The antenatal history was uneventful.

Birth history

The birth history was third degree consanguinous a

marriage, term, LSCS, birth weight of 3 kgs, cried
immediately after birth.

Immunization history

No immunizations were taken (at birth and other

vaccination).

Anthropometry

Weight=5 kgs (3-50th centile), length=55 cm (1-3

centile), HC:40 cms (50th centile). On examination child
was looking sick, dull. PR=153 bpm, RR=53 cpm,
RESP=wheeze present, b/l crepts present, subcostal b
retractions present, inspiratory stridor present, CFT
<3secs, CVS and CNS were normal. Baby was shifted to Figure 1 (a and b): Chest X-ray of mild cardiomegaly.
PICU and started on oxygen support via HHHFNC, IV
antibiotics, IV fluids and other supportive care. Antenatal history

Hemogram The antenatal history was uneventful.

The hemogram was normal. CRP=positive (24). Blood Birth history

culture and sensitivity=showed no growth after 48 hours
of aerobic incubation. Initial ABG was suggestive of pH- The birth history was born of second degree
7.376, HCO3=9.7, pCO2=28 mmhg, pO2=85.6 mmhg, consanguinous marriage, term, 2.5 kg, LSCS, cried
lactate=8.4. LFT showed increase in alkaline phosphate. immediately after birth. History of NICU admission for
2D echo showed severe PH with RVSP=55 mmhg, NNJ for 1 day.
dilated right atrium, dilated right ventricle with right
ventricular dysfunction. Thiamine levels were evaluated Immunization
which showed 11 ng/dl .
BCG scar was present on left deltoid and vaccination
Baby was started on milrinone and sildenafil infusions upto 14 weeks were done.
and gradually tapered. Baby was initiated on trial of
thiamine which showed significant improvement in Anthropometry
baby’s condition. Repeat 2D echo showed decrease in
RSVP=19 mmhg and no pulmonary artery hypertension. The anthropometry was weight=6 kgs, length=69 cm,
Later with improving saturations baby was weaned off HC=42 cms. On examination baby was conscious,
from HHHFNC to low flow O2 and then to room air.

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irritable, PR=145 bpm, RR=64 cpm, RESP=wheeze Antenatal history

present, b/l ronchi with crepts present, subcostal
retractions present, P/A=soft no tenderness, liver The antenatal history was uneventful.
palpable 2 cm below right subcostal margin, liver span=8
cm, CVS and CNS were normal. Baby was shifted to Birth history
PICU i/v/o respiratory distress with tachypnoea and
subcostal retractions and started on oxygen support via The birth history was born of non consanguinous
HHHFNC and supportive care was given. marriage, term, 2.8 kgs, LSCS, cried immediately after
birth. History of NICU admission for NNJ for 1 day.
Hemogram
Immunization
The hemogram was normal and CRP=negative. 2D echo
showed mild pulmonary hypertension with mildly dilated BCG scar present on left deltoid and vaccination upto 14
RA and RV, RSVP=65 mmhg and no dysfunction of right weeks were done.
ventricle. X-ray has shown mild cardiomegaly. Thiamine
levels were sent for evaluation and showed 17 ng/dl. Anthropometry

Baby was started on tablet sildenafil, injection thiamine The anthropometry was weight=4.5 kgs, length=62 cm,
and other supportive care. Baby showed clinical HC=40 cms. On examination baby was conscious,
improvement and there was no distress or fever spikes irritable, temperature=98.6◦F PR=166 bpm, RR=62 cpm,
during the hospital stay. Repeat 2D echo showed RESP=wheeze present, b/l ronchi with crepts present,
decrease in pressure PSVP=22 mmhg and no PH. subcostal retractions present, P/A=soft no tenderness,
liver palpable 1 cm below right subcostal margin, liver
Later saturations were maintained and baby was weaned span=7 cm, CVS and CNS were normal. Baby was
off from HHHFNC to low flow O2 and then to room air. shifted to PICU i/v/o respiratory distress with tachypnoea
and subcostal retractions and started on oxygen support
via HHHFNC.

Hemogram

The hemogram was normal and CRP=negative. 2D echo

showed mild PH with mildly dilated RA and RV,
RSVP=48 mmhg and no dysfunction of right ventricle.
Thiamine levels were not sent for evaluation as parents
were not willing due to financial constraints. Baby was
started on tablet sildenafil, injection thiamine and other
supportive care. Baby showed clinical improvement and
there was no distress or fever spikes during the hospital
stay. Patients attenders were not affordable for chest X-
ray and 2D echo. So patient was monitored accordingly
and later when saturations were maintained and baby was
weaned off from HHHFNC to low flow O2 and then to
room air and discharged when patient has improved
symptomatically and was active.
Figure 2: Chest X-ray of mild cardiomegaly.
Follow up
Case 3
On follow up for 3 months, all the babies recovered and
A 4 month old male baby was brought to EMD with their repeat 2D echo and blood tests of first two cases
complaints of cough and cold, increase work of breathing were normal. They were symptomatically stable
and decrease intake of feeds since 4 days, shortness of constitutional symptoms. The babies along with their
breath since 1 day. mothers were prescribed thiamine tablets for 6 months.
On follow up for another 6 months they remained well
No similar complaints were there in the past. No and their symptoms fully resolved.
significant family history or history of any chronic
respiratory illness. Differential diagnosis4

Encephalitis, cardiomyopathy, meningitis, metabolic

encephalopathy, respiratory and metabolic acidosis of
any etiology, congenital heart disease.

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Table 1: Clinical presentation of three cases of thiamine-responsive acute pulmonary hypertension of early infancy.

Case report 1 Case report 2 Case report 3

Age 2 months 5 months 4 months
Gender Male Female Male
Birth weight 3 kgs 2.5 kgs 2.8 kgs
Current weight 5 kgs 4.7 kgs 4.5 kgs
Consanguinity Yes (third degree) Yes (second degree) No
Family history Not significant Not significant Not significant
Increased work of breathing, Cold and cough, increase
Increased work of
decrease in urine output and work of breathing,
Initial S/S breathing, cough and
cold and cough, decrease decrease of feeds and
cold, poor feeding
intake of feeds and fever lose stools
Heart rate 153 bpm 145 bpm 166 bpm
Respiratory rate 53 cpm 64 cpm 62 cpm
Polished rice and food
Maternal diet Polished rice Polished rice
avoidance postpartum
Severity of PH Severe Mild Mild
2D echo
RVSP before thiamine
55 mmhg 65 mmhg 48 mmhg
infusion
RVSP after thiamine
19 mmhg 22 mmhg -
infusion
Respiratory support given HHHFNC HHHFNC HHHFNC
Pulmonary vasodilators used Injection sildenafil Tablet sildenafil Tablet sildenafil
Circulatory support Milrinone - -
Thiamine levels
Mother 20 ng/dl - -
Infant 11 ng/dl 17 ng/dl -
Response to thiamine
weaned to room air 5 days 2 days 3 days
improvement seen within
5 hours 5 hours 4 hours
Resolution seen by
1 week 3 days 4 days

DISCUSSION consanguineous marriage and one did not receive regular

vaccinations.
The review of literature including our patients have
shown infantile PH due to thiamine deficiency, which is Thiamine deficiency can cause wet beri beri which leads
mostly seen in developing countries like South Asian, to cardiac dysfunction but PH in beri beri patients is
African and other sub continents and very few cases have extremely rare.2
been noticed in developed countries like UK and USA. 3
Main source of thiamine in developing countries includes There are 2 proposed theories showing us the
rice, whole grains, poultry, nuts, soyabeans.5 The mechanisms by which thiamine deficiency can cause
recommended daily intake (RDI) levels in infancy are 0.2 pulmonary hypertension. Thiamine deficiency leads to
mg/day and its RDI levels slightly increase with age.5 cardiac dysfunction (left) which causes decrease in
From the above cases we reported the factors leading to cardiac output and back flow of accumulated blood,
thiamine deficiency can be due to excessive use of increased pressure in pulmonary veins. This leads to PH
polished rice (rice is rinsed many times under running and right heart failure (bi-ventricular dysfunction).6 In
water before it being cooked-one of the reason for B1 another proposed theory, thiamine deficiency leads to
loss along with washed water), food avoidance by generation of super oxide ions which results in decrease
mothers and exclusive breast feeding, similarly these in production of nitric oxide, vasoconstriction of
were one of the factors reported by other studies.2,3 pulmonary arteries, thereby causing PH.3 Criteria
Infants who are in rapid growth phase and increased considered for diagnosing infantile thiamine responsive
metabolic rate still require higher levels to maintain the pulmonary hypertension were it’s a denovo diagnosis of
bodily functions. From our three cases two were from a PH2; no other relatable cause for PH3; patient may be
presenting with metabolic acidosis along with lactic

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 Venkat CG et al. Int J Contemp Pediatr. 2021 Jun;8(6):1102-1106

acidosis4; mothers who are exclusively breast feeding A similar case of a 3 months old baby was reported in
have thiamine deficient diet5; rapid response over hours Africa presented with pneumonia and thiamine treatment
to days to week to thiamine. was given as a last resort due to economic/financial
constraints and lack of early diagnosis. The baby had
All our cases presented to EMD with signs and symptoms exaggerated symptoms of PH as baby was initially on
of typical pulmonary hypertension with accompanying dextrose fluids on first 48 hours that lead to severe
respiratory illness. The frequent complaints were deficiency.1
increased work of breathing, shortness of breath,
tachypnoea and one of our case even had tachycardia. On CONCLUSION
examination the patients had wheeze, crepts, rhonchi and
inspiratory stridor along with subcoastal retractions. 2D Thiamine deficiency is still a deficiency that requires a
echo of all cases had shown bi-ventricular failure with spotlight before serious consequences occur in an infant
dilated RA and RV. Case 1 had similar complaints in past like cardiac and pulmonary conditions. Infantile
but due to unrecognized thiamine deficiency baby had pulmonary hypertension is a budding disease with
progressed to severe PH. All our patients were given immediate recognition and treatment.
respiratory support by HHHFNC. On infusion of
thiamine there was rapid improvement in patients within Funding: No funding sources
4-5 hours. The patients were continued post discharge on Conflict of interest: None declared
oral thiamine for 6 months and mothers were asked to Ethical approval: Not required
continue supplements till babies were on breast feeding.
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in our case 1. Cite this article as: Venkat CG, Pujitha VC,
Channawar KS, Vasavi V. Thiamine responsive
pulmonary hypertension: case series. Int J Contemp
Pediatr 2021;8:1102-6.

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