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. 2022 Oct 27;12(11):1721.
doi: 10.3390/life12111721.

Three-Country Snapshot of Ornithine Transcarbamylase Deficiency

Berna Seker Yilmaz  1 , Julien Baruteau  1   2   3 , Nur Arslan  4 , Halil Ibrahim Aydin  5 , Magalie Barth  6 , Ayse Ergul Bozaci  7 , Anais Brassier  8 , Ebru Canda  9 , Aline Cano  10 , Efstathia Chronopoulou  11 , Grainne M Connolly  12 , Lena Damaj  13 , Charlotte Dawson  14 , Dries Dobbelaere  15 , Claire Douillard  15 , Fatma Tuba Eminoglu  16 , Sahin Erdol  17 , Melike Ersoy  18 , Sherry Fang  3 , François Feillet  19 , Gulden Gokcay  20 , Emine Goksoy  21 , Magali Gorce  22 , Asli Inci  23 , Banu Kadioglu  24 , Fatih Kardas  25 , Cigdem Seher Kasapkara  26 , Gonca Kilic Yildirim  27 , Deniz Kor  28 , Melis Kose  29 , Cecilia Marelli  30   31 , Helen Mundy  32 , Siobhan O'Sullivan  33 , Burcu Ozturk Hismi  34 , Radha Ramachandran  35 , Agathe Roubertie  30   31 , Mehtap Sanlilar  36 , Manuel Schiff  8 , Srividya Sreekantam  37 , Karolina M Stepien  38 , Ozlem Uzun Unal  39 , Yilmaz Yildiz  40 , Tanyel Zubarioglu  41 , Paul Gissen  1   2   3
Affiliations

Three-Country Snapshot of Ornithine Transcarbamylase Deficiency

Berna Seker Yilmaz et al. Life (Basel). .

Abstract

X-linked ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle defect. The disease severity ranges from asymptomatic carrier state to severe neonatal presentation with hyperammonaemic encephalopathy. We audited the diagnosis and management of OTCD, using an online 12-question-survey that was sent to 75 metabolic centres in Turkey, France and the UK. Thirty-nine centres responded and 495 patients were reported in total. A total of 208 French patients were reported, including 71 (34%) males, 86 (41%) symptomatic and 51 (25%) asymptomatic females. Eighty-five Turkish patients included 32 (38%) males, 39 (46%) symptomatic and 14 (16%) asymptomatic females. Out of the 202 UK patients, 66 (33%) were male, 83 (41%) asymptomatic and 53 (26%) symptomatic females. A total of 19%, 12% and 7% of the patients presented with a neonatal-onset phenotype in France, Turkey and the UK, respectively. Vomiting, altered mental status and encephalopathy were the most common initial symptoms in all three countries. While 69% in France and 79% in Turkey were receiving protein restriction, 42% were on a protein-restricted diet in the UK. A total of 76%, 47% and 33% of patients were treated with ammonia scavengers in Turkey, France and the UK, respectively. The findings of our audit emphasize the differences and similarities in manifestations and management practices in three countries.

Keywords: ammonia scavengers; asymptomatic; hyperammonaemia; late-onset; liver transplantation; neonatal-onset; ornithine transcarbamylase deficiency; protein restriction.

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Conflict of interest statement

PG is an academic co-founder of Bloomsbury Genetic Therapies, UCL spinout developing a gene programme in OTC deficiency.

Figures

Figure 1
Figure 1
Gender distribution of OTCD patients in France, Turkey and the UK. Blue: male; orange: female asymptomatic; grey: female symptomatic.
Figure 2
Figure 2
Age groups of OTCD patients in France, Turkey and the UK. Blue:0–6 years old; orange:6–12 years old; grey: 12–18 years old; yellow: >18 years old.
Figure 3
Figure 3
Clinical phenotypes of OTCD patients in France, Turkey and the UK. Blue: Neonatal presentation; orange: late-onset presentation; grey: asymptomatic.
Figure 4
Figure 4
Initial clinical symptoms of OTCD patients in France, Turkey and the UK. Percentages of reported initial clinical symptoms. In blue France; in orange Turkey; in grey the UK.
Figure 5
Figure 5
Protein restriction in OTCD patients in France, Turkey and the UK. Blue: Protein restriction; orange: no protein restriction.
Figure 6
Figure 6
Ammonia scavenger usage in OTCD patients in France, Turkey and the UK. Yellow: sodium benzoate usage; green: sodium/glycerol phenylbutyrate usage; orange–red: dual therapy (sodium benzoate and sodium/glycerol phenylbutyrate) usage; orange: no-scavengers. SB: sodium benzoate; SPB: sodium phenylbutyrate; GPB: glycerol phenylbutyrate 3%, 6% and 7% of the patients underwent liver transplantation in France, Turkey and the UK, respectively.
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