Obstetric implications of being an ornithine transcarbamylase (OTC) deficiency carrier - a case series

A case series looking at two cases and the successful obstetric management of the rare metabolic disorder OTC deficiency, at York hospital in March 2022.

Authors Dr Thomas Hanton, Miss Jacqueline Tang

Affiliations York and Scarborough Teaching Hospitals NHS Foundation Trust, York Hospital, Wigginton Road, Clifton, York, YO31 8HE, United Kingdom

Acknowledgements 

Dr Gisela Wilcox (Consultant in medical biochemistry and metabolic medicine at The Mark Holland Metabolic Unit, Salford Royal Foundation HHS Trust).

Dr Emily Christie (Consultant in anaesthetics at York and Scarborough Teaching Hospitals NHS Foundation Trust).

Introduction

Ornithine Transcarbamylase deficiency is an X-linked with variable phenotypic expression in females who carry the disease. Ornithine transcarbamylase is one of six enzymes in the urea cycle, a process which converts ammonia into urea (1).

Objective

This case series of two women with heterozygous OTC (Ornithine transcarbamylase) deficiency who had successful deliveries in March 2022 at York hospital. Managing this very rare metabolic disorder is complex and involves input from a wider MDT.

Case 1

31-year-old lady, P2G5, who has heterozygous OTC deficiency, who successfully delivered a female baby in March 2022. She has a 5-year-old daughter who is an asymptomatic OTC carrier and sadly had a neonatal death of her son at 4-days postpartum. In this pregnancy she had a NIPT which revealed she was carrying a female fetus. She declined further invasive testing of her fetus. On postnatal testing her daughter was found to have heterozygous OTC deficiency.

Case 2

29-year-old lady, P2G7, who has heterozygous OTC deficiency, who successfully delivered a male baby in March 2022. She has a 4-year-old son who was diagnosed OTC deficiency presenting with hyperammonaemia neonatally and had a successful liver transplant at 6 months old. In this pregnancy she had a NIPT which revealed she was carrying a male fetus. She underwent invasive testing with a CVS which revealed that the pregnancy had not inherited the OTC gene alteration.

Key drugs - to aid excretion of nitrogen

• Sodium benzoate - Forms hippurate which is excreted in the urine
• Sodium phenylbutyrate - Forms phenylacetylglutamine which is excreted in the urine
• L-Arginine - To replace arginine which cannot be synthesised in the urea cycle

 

The drugs should be made up in 10% glucose in either a 50 ml syringe or 500 ml bag (maximum concentration 2.5g in 50mls or 25 g in 500 ml bag) and given by a syringe pump or by an infusion pump (2). These drugs are only to be given for immediate emergency management prior to seeking advice from the local metabolic disease centre.

See BIMDG (British Inherited Metabolic Disease Group) guidelines for exact doses and infusion rates (3) (4).

Obstetric management plan for OTC deficiency carriers

In order to aid with the management of this rare metabolic disorder during pregnancy, a management plan has been created with input from specialists in: obstetrics; anaesthetics; metabolic disease; and dieticians. In addition, further input and advice around the management of the above cases was made with paediatricians and geneticists.

Antenatal care

• Serial fetal growth scans
• Monthly ammonia levels
• MDT management plan alongside Metabolic disease centre
• Amino acid profile to be done at metabolic disease centr
• Vitamin replacement (Solvazinc 1 tablet BD, Vitamin B12 replacement, Vitamin D replacement)
• Paediatrics referral
• CT head and ophthalmology review to assess for raised ICP.

Intrapartum care

• Prepare key drugs (see key drugs and BIMDG guidelines)
• Consider epidural in the first stage of labour to blunt the stress response (avoid if raised ICP)
• Avoid exhaustion and prolonged labour. Avoid a prolonged second stage, can have a passive 1 hour second stage but active second stage should be limited to 1 hour with instrumental delivery considered after 1 hour of active second stage.
• Maintain 2000kcals of protein free calories.
• For Caesarean sections patients should take their usual medicines orally until the point of fasting. Once fasting IV 10% dextrose +/- electrolytes should be started at 125mls/hr pre- and post-partum until oral intake is satisfactory.
• Caesarean section can be performed under epidural, spinal or GA, but raised ICP must be excluded.
• Cord bloods should be taken with a genetic request form to check the baby’s OTC gene variant status.