1 PMH PMH Medical HxP: Pregnancy: Normal, no drugs taken - - PDF document

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Pediatric Pulmonary Arterial Hypertension: Case Presentation

Susan Richards RN, MN, NP Pediatric Pulmonary Hypertension, Stollery Children’s Hospital 2

Objectives

• Case presentation
• Brief review of the topic
• Review of the literature- issues surrounding the case

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Case Presentation

• J.K. , 4/12 male

PC

• Peripheral and central cyanosis. Sats okay with

supplemental O2 4L. Mod to severe resp. distress

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HPC

• January 15 2018: History of coughing since January 10

2018, greyish appearance prior to this time. CXR: suggestive for cardiac enlargement. No pulmonary disease.

• January 21 2018: Cardiac enlargement; no pulmonary
• disease. Desaturations into low 80’s (responsive to O2).
• January 22 2018: Transferred to Stollery Children's

Hospital ER. – Resp Distress – FTT (3.5kg) – Sats okay on 4L NC

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PMH

• Pregnancy: Normal, no drugs taken
• Perinatal/Delivery: SVD, no complications, 2100grams

(approx 4lbs 10 oz)

• Postnatal: 24 hours post delivery cyanotic (Sats low

70%), RR 100, normal BS, septic workup, abx – 0.00 neutrophil – WBC 0.8 – NP aspirate: + Human metapneumovirus

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PMH

• Medical HxP:

– G6PC3 deficiency – ASD – Undescended testicles – Small for gestational age – Osteopetrosis – FTT

• Med: G-CSF
• Allergies: NKA
• Immunizations: none

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FH/SH

• First Child
• Caucasian
• No one in family with known genetic defect
• No Hx of consanguinity
• Parents healthy (young)
• Lives in a Hutterite Colony Rural Alberta
• No recent travel

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O/E

• General: Alert, irritable with examination,

adequate head control. Wt 3.6kg /Ht: 59 cm

• CNS: Anterior fontanelle soft
• Resp: 40-50 mild in-drawing; suprasternal, tracheal tug.

Cry, squeaky but audible 2L O2

• CVS: WWP centrally; cool extremities.HR 109-157

SR;S2 split with increase P2; mild RV heave

• Abdomen: Liver 1 cm below RCM GU: undescended

testes

• Skin: superficial venous angiectasis

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CXR

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ECG

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ECHO

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Investigations

• CXR: Cardiac Enlargement; lung and pleural spaces

clear

• ECG: SR, RAE, RVH, and LVH by voltage; towards

RAD

• Echocardiogram: small secundum ASD; bidirectional

shunting RVSp 74 mmHg+Rap (SBP 98mmHg); PR mean PAp 32 mmHg; RVFAC 13%; small pericardial effusion.

• Blood work: WBC 34.1; Neut.,30.2; ALT 72; NTproBNP

1624.0 pmol/L; Blood Culture,neg; NP aspirate;+ Human metapnemovirus &entero-rhinovirus;

• MRSA, neg

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Management

• Echocardiogram assessing pulmonary veins.
• Start sildenafil 0.25 mg/kg x2 doses. Then 0.5 mg/kg x2

doses, and then 1 mg/kg per dose q8h

• Aldactazide1mg/kg BID.
• Add in ETA
• Hematology to follow neutropenia

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Pro Beta Natriuretic Peptide

NT proBNP Test Number 1 2 3 4 5 Collection Date 24-Jan-18 02-Feb-18 08-Feb-18 21-Feb-18 13-Mar-18 pmol/L 1624.0 162.5 67.3 92.7 211.1

200 400 600 800 1000 1200 1400 1600 1800 1 2 3 4 5

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G6P Classification

General Points

• Genetic disease autosomal recessive mutations on

17q21.31

• Member of G6P family

– G6PC1 (liver, gut and kidney) – G6PC2 (pancreas)

• G6PC3 ubiquitously: Features congenital neutropenia,

superficial skin venous pattern heart and urogenital, SHNL, FTT,PAH, cognitive impairment and/or endocrine abn

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G6PC3 Pathophysiology

• Glucose-6-phosphatase enzyme is located in the

endoplasmic reticulum (ER) and hydrolyses glucose-6- phosphate to glucose and phosphate.

• Loss of G6PC3 function shown to result in prevention of

glucose recycling from the ER to the cytoplasm in the neutrophil

• Loss of G6PC3 activity also shown to increased

susceptibility to apoptosis in skin fibroblasts, neutrophils, and myeloid cells

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Pathophysiology Con’t

• Identification of the genetic basis of Dursun syndrome

adds to the existing knowledge that mutations in G6PC3 can cause PPH.

• PPH is a known complication of type 1 glycogen

storage and establishing PPH as part of SCN4 phenotype may suggests an important link between glucose metabolism and PPH.

• Further studies needed

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G6PC3 Deficiency

• Mutations in G6PC3 cause SCN4.
• Recurrent infections and prominent superficial venous

pattern are the most frequent clinical features

• Congenital heart defects and urogenital malformations
• Dursun syndrome is triad of familial PPH, leucopenia,

and ASD.

• Dursun syndrome expands the pre-existing knowledge
• f the phenotypic effects of mutations in G6PC3
• Should Dursun syndrome be considered as a subset of

SCN4 with PPH as an important clinical feature?

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Management/Challenges

• Treatment with G-CSF
• Bacterial and viral infections
• Pulmonary vasodilator (s)
• Timing of images and invasive procedures
• Size of ASD
• No immunizations
• Medication compliance
• Multidisciplinary team approach

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References

• Boztug, K.,et al. A syndrome with congenital neutropenia and mutations in G6PC3. New Eng. J. Med. 360: 32-

43, 2009.

• McDermott, D. H., et al. Severe congenital neutropenia resulting from G6PC3 deficiency with increased

neutrophil CXCR4 expression and myelokathexis. Blood 116: 2793-2802, 2010.

• Arikoglu, T., et al. A novel G6PC3 gene mutation in severe congenital neutropenia: pancytopenia and variable

bone marrow phenotype can also be part of this syndrome. European Journal of Hematology. 94: 79-82, 2014.

• Banka, S. & Newman, W. A clinical and molecular review of ubiquitous glucose-6-phosphatase deficiency

caused by G6PC3 mutations. Journal of Rare Diseases. 8:84 1-17, 2013.

• Banka, S., et al. Mutations in the G6PC3 Gene Cause Dursun Syndrome. American Journal of Medical Genetics.

52A:2609–2611, 2010

• Lammers, A. et al. Diagnostics, monitoring and outpatient care in children with suspected pulmonary

hypertension/paediatric pulmonary hypertensive vascular disease. Expert consensus statement on the diagnosis andtreatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease. Heart BMJ. 102:ii1-ii13, 2016.

• Kozlik-Feldmann, R., et al. Pulmonary hypertension in children with congenital heart disease (PAH-CHD,

PPHVD-CHD). Expert consensus statement on the diagnosis and treatment of paediatric pulmonary

• hypertension. The European Paediatric Pulmonary Vascular Disease. Heart BMJ. 102:ii42-ii48, 2016.