Evaluation of Patients Diagnosed with Congenital Glycosylation Defects: A Rainbow of Inherited Metabolic Disorders

Sebile Kılavuz; Fatma Derya Bulut; Deniz Kor; Berna Şeker; Atıl Bişgin; Fadli Demir; Bahriye Atmış; Derya Alabaz; H. Neslihan Önenli Mungan

Makale detayları

Evaluation of Patients Diagnosed with Congenital Glycosylation Defects: A Rainbow of Inherited Metabolic Disorders

Yazarlar:

Sebile Kılavuz | Fatma Derya Bulut | Deniz Kor | Berna Şeker | Atıl Bişgin | Fadli Demir | Bahriye Atmış | Derya Alabaz | H. Neslihan Önenli Mungan

Yayıncı:

Istanbul University

Ana Başlıklar:

Klinik Tıp Bilimleri (Diğer)

Dergi:

Çocuk Dergisi Vol.23 Issue 3, pp.233-242

Belge Tipi:

Makale

Yayın Tarihi:

10/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001303682

pISSN:

1308-8491

Anahtar kelimeler:

Özet:

 Introduction: Congenital glycosylation defects CDGs manifest with multisystemic symptoms involving the immune, central nervous, endocrine, and musculoskeletal systems. A total of 137 distinct CDG types have been identified to date. Materials and Methods: Patients diagnosed with CDG in the Division of Pediatric Metabolism and Nutrition, at Çukurova University, between 2013 and 2019 were included in the study. The patients files were retrospectively reviewed, and demographic, clinical, laboratory and radiological findings and molecular analyses were recorded and evaluated. Results: The mean age at diagnosis for a total of 11 6 Female; 5 Male patients Four with PMM2-CDG, one with MPI-CDG, one with DOLK-CDG, one with B4GALT1-CDG, three with TMEM165-CDG, and one with PIGNCDG was 6.94 years ranging from 11 months to 22 years. Amongst the patients, 45 5 individuals were male. Sixty-three percent of patients exhibited low weight and height below the 5th percentile. Elevated liver enzymes were observed in 82 of cases, while 82 showed neurodevelopmental delay, 72 had cerebellar atrophy, and 72 experienced growth retardation. Additionally, 73 of patients displayed hepatomegaly and thrombocytopenia, and 63 had renal involvement. An homozygous p.V129M c.385GA mutation in the PMM2 gene confirmed PMM2-CDG diagnosis in four patients. Furthermore, distinct homozygous mutations were detected: p. I399T c.1193TC in the MPI gene, p. Y441S c.1322AC in the DOLK gene, p. Arg126Cys c.376CT in the TMEM165 gene, a novel p. Tyr239 c.717TG mutation in the B4GALT1 gene, and a novel p. Thr266Ala c.2356AG mutation in the PIGN gene. Conclusion: CDGs exhibit a diverse clinical spectrum, earning them the moniker the rainbow of hereditary metabolic disorders. While PMM2- CDG is the most prevalent subtype, only a few instances of other subtypes have been documented. Inverted nipples and abnormal fat pads are primary features of CDGs. The intricate nature of our cases and the rarity of DOLK-CDG, PIGN-CDG, and TMEM-165-CDG diagnoses stand out as notable aspects of this report.

 Introduction: Congenital glycosylation defects CDGs manifest with multisystemic symptoms involving the immune, central nervous, endocrine, and musculoskeletal systems. A total of 137 distinct CDG types have been identified to date. Materials and Methods: Patients diagnosed with CDG in the Division of Pediatric Metabolism and Nutrition, at Çukurova University, between 2013 and 2019 were included in the study. The patients files were retrospectively reviewed, and demographic, clinical, laboratory and radiological findings and molecular analyses were recorded and evaluated. Results: The mean age at diagnosis for a total of 11 6 Female; 5 Male patients Four with PMM2-CDG, one with MPI-CDG, one with DOLK-CDG, one with B4GALT1-CDG, three with TMEM165-CDG, and one with PIGNCDG was 6.94 years ranging from 11 months to 22 years. Amongst the patients, 45 5 individuals were male. Sixty-three percent of patients exhibited low weight and height below the 5th percentile. Elevated liver enzymes were observed in 82 of cases, while 82 showed neurodevelopmental delay, 72 had cerebellar atrophy, and 72 experienced growth retardation. Additionally, 73 of patients displayed hepatomegaly and thrombocytopenia, and 63 had renal involvement. An homozygous p.V129M c.385GA mutation in the PMM2 gene confirmed PMM2-CDG diagnosis in four patients. Furthermore, distinct homozygous mutations were detected: p. I399T c.1193TC in the MPI gene, p. Y441S c.1322AC in the DOLK gene, p. Arg126Cys c.376CT in the TMEM165 gene, a novel p. Tyr239 c.717TG mutation in the B4GALT1 gene, and a novel p. Thr266Ala c.2356AG mutation in the PIGN gene. Conclusion: CDGs exhibit a diverse clinical spectrum, earning them the moniker the rainbow of hereditary metabolic disorders. While PMM2- CDG is the most prevalent subtype, only a few instances of other subtypes have been documented. Inverted nipples and abnormal fat pads are primary features of CDGs. The intricate nature of our cases and the rarity of DOLK-CDG, PIGN-CDG, and TMEM-165-CDG diagnoses stand out as notable aspects of this report.

 Introduction: Congenital glycosylation defects CDGs manifest with multisystemic symptoms involving the immune, central nervous, endocrine, and musculoskeletal systems. A total of 137 distinct CDG types have been identified to date. Materials and Methods: Patients diagnosed with CDG in the Division of Pediatric Metabolism and Nutrition, at Çukurova University, between 2013 and 2019 were included in the study. The patients files were retrospectively reviewed, and demographic, clinical, laboratory and radiological findings and molecular analyses were recorded and evaluated. Results: The mean age at diagnosis for a total of 11 6 Female; 5 Male patients Four with PMM2-CDG, one with MPI-CDG, one with DOLK-CDG, one with B4GALT1-CDG, three with TMEM165-CDG, and one with PIGNCDG was 6.94 years ranging from 11 months to 22 years. Amongst the patients, 45 5 individuals were male. Sixty-three percent of patients exhibited low weight and height below the 5th percentile. Elevated liver enzymes were observed in 82 of cases, while 82 showed neurodevelopmental delay, 72 had cerebellar atrophy, and 72 experienced growth retardation. Additionally, 73 of patients displayed hepatomegaly and thrombocytopenia, and 63 had renal involvement. An homozygous p.V129M c.385GA mutation in the PMM2 gene confirmed PMM2-CDG diagnosis in four patients. Furthermore, distinct homozygous mutations were detected: p. I399T c.1193TC in the MPI gene, p. Y441S c.1322AC in the DOLK gene, p. Arg126Cys c.376CT in the TMEM165 gene, a novel p. Tyr239 c.717TG mutation in the B4GALT1 gene, and a novel p. Thr266Ala c.2356AG mutation in the PIGN gene. Conclusion: CDGs exhibit a diverse clinical spectrum, earning them the moniker the rainbow of hereditary metabolic disorders. While PMM2- CDG is the most prevalent subtype, only a few instances of other subtypes have been documented. Inverted nipples and abnormal fat pads are primary features of CDGs. The intricate nature of our cases and the rarity of DOLK-CDG, PIGN-CDG, and TMEM-165-CDG diagnoses stand out as notable aspects of this report.

 Giriş: Konjenital glikozilasyon kusurları CDG, immün, merkezi sinir, endokrin ve kas-iskelet sistemlerini içeren multi sistemik belirtilerle ortaya çıkar. Bugüne kadar toplamda 137 farklı CDG türü tespit edilmiştir. Materyal ve Metod: Çukurova Üniversitesi Çocuk Metabolizma ve Beslenme Bilim Dalında 2013 ve 2019 yılları arasında takip edilen ve CDG tanısı alan hastalar çalışmaya dahil edildi. Hastaların kayıtları geriye dönük olarak incelendi ve demografik klinik, laboratıvar ve radyolojik bulguları kayıt edilerek değerlendirildi. Bulgular: Toplam 11 hastanın Dört PMM2-CDG, bir MPI-CDG, bir DOLKCDG, bir B4GALT1-CDG, üç TMEM165-CDG ve bir PIGN-CDG tanı anındaki ortalama yaşları 6.94 yıl 11 ay ile 22 yıl arası idi. Hastaların 45i 5 kişi erkekti. Hastaların 63ünde ağırlık ve boy, 5. persentilin altında bulunmaktaydı. 82sinde yüksek karaciğer enzimleri, 82sinde nörogelişimsel gecikme, 72sinde serebellar atrofi ve 72sinde büyüme geriliği gözlendi. Ek olarak, hastaların 73ünde hepatomegali ve trombositopeni, 63ünde ise böbrek tutulumu tespit edildi. PMM2 genindeki homozigot p.V129M c.385GA mutasyonu, 4 hastada PMM2-CDG tanısını doğruladı. Ayrıca, MPI geninde p. I399T c.1193TC homozigot mutasyonu, DOLK geninde p. Y441S c.1322AC homozigot mutasyonu, TMEM165 geninde p. Arg126Cys c.376CT homozigot mutasyonu, B4GALT1 geninde novel bir p.Tyr239 c.717TG mutasyonu ve PIGN geninde novel bir p. Thr266Ala c.2356AG mutasyonu tespit edildi. Sonuç: Konjenital glikozilasyon defektleri çeşitli klinik spektruma sahip olup, onları genetik metabolik bozuklukların gökkuşağı olarak adlandırmamıza sebep olmaktadır. Çalışmamızda PMM2-CDG en yaygın görülen tip iken, diğer tiplerden sadece birkaç örnek bulunmaktadır. Konjenital glikozilasyon defektlerinin ana özellikleri arasında ters meme uçları ve anormal yağ yastıkçıkları yer almaktadır. Vakaların karmaşıklığı ve DOLK-CDG, PIGNCDG ve TMEM-165-CDG tanılarının nadirliği, bu araştırmanın dikkat çeken yönlerini oluşturmaktadır.

Makale detayları

Evaluation of Patients Diagnosed with Congenital Glycosylation Defects: A Rainbow of Inherited Metabolic Disorders

Yazarlar:

Sebile Kılavuz | Fatma Derya Bulut | Deniz Kor | Berna Şeker | Atıl Bişgin | Fadli Demir | Bahriye Atmış | Derya Alabaz | H. Neslihan Önenli Mungan

Yayıncı:

Istanbul University

Ana Başlıklar:

Klinik Tıp Bilimleri (Diğer)

Dergi:

Çocuk Dergisi Vol.23 Issue 3, pp.233-242

Belge Tipi:

Makale

Yayın Tarihi:

10/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001303682

pISSN:

1308-8491

glycosylation

congenital glycosylation defects

PMM2

MPI

DOLK

TMEM-165

PIGN

CDglikozilasyon

konjenital glikozilasyon kusurları

PMM2

MPI

DOLK

TMEM-165

PIGN

CDG

Sayı

Makale detayları

Yazarlar: Sebile Kılavuz | Fatma Derya Bulut | Deniz Kor | Berna Şeker | Atıl Bişgin | Fadli Demir | Bahriye Atmış | Derya Alabaz | H. Neslihan Önenli Mungan

Yayıncı: Istanbul University

Ana Başlıklar: Klinik Tıp Bilimleri (Diğer)

Dergi: Çocuk Dergisi Vol.23 Issue 3, pp.233-242

Belge Tipi: Makale

Yayın Tarihi: 10/2023

Belge Dili: İngilizce

Document ID (Org No.): 2001303682

pISSN: 1308-8491

Sayı

Yazarlar:

Sebile Kılavuz | Fatma Derya Bulut | Deniz Kor | Berna Şeker | Atıl Bişgin | Fadli Demir | Bahriye Atmış | Derya Alabaz | H. Neslihan Önenli Mungan

Yayıncı:

Istanbul University

Ana Başlıklar:

Klinik Tıp Bilimleri (Diğer)

Dergi:

Çocuk Dergisi Vol.23 Issue 3, pp.233-242

Belge Tipi:

Makale

Yayın Tarihi:

10/2023

Belge Dili:

İngilizce

Document ID (Org No.):

2001303682

pISSN:

1308-8491