Erişkin Yaşta Tanı Alan Kalıtsal Metabolik Hastalıklar: Tek Merkez Deneyimi

Öz

Kalıtsal metabolik hastalıklar (KMH) geleneksel olarak çocukluk çağında başlayan hastalıklar olarak kabul edilmekle birlikte, giderek artan sayıda hasta adolesan ve erişkin dönemde tanı almakta ve sıklıkla heterojen ve özgül olmayan klinik bulgularla başvurmaktadır. Bu çalışmada, geçiş yaşı ve erişkin dönemde tanı alan KMH’li hastalarda klinik spektrumun, biyokimyasal bulguların, genetik tanıların ve tedavi yaklaşımlarının değerlendirilmesi amaçlanmıştır. Bu retrospektif çalışmaya KMH tanısı almış 18 hasta dahil edilmiştir. ≥16 yaşındaki bireyler, pediatrik ve erişkin dönem arasındaki örtüşmeyi yansıtmak amacıyla geçiş yaşı olarak tanımlanmıştır. Demografik, klinik, biyokimyasal ve genetik veriler toplanmış; uygulanan tedavi yaklaşımları kaydedilmiştir. Tanısal değerlendirme, hastalığa özgü biyokimyasal testler ve moleküler genetik analizlerle gerçekleştirilmiştir. Çalışma grubunda 10 kadın ve 8 erkek hasta yer almakta olup, ortalama tanı yaşı 34,2 yıl (dağılım: 16–61 yıl) olarak bulunmuştur. Tanı spektrumu heterojen olup en sık tanı alkaptonüri (n=4) olarak saptanmış, bunu glikojen depo hastalığı tip V (n=2) izlemiştir; diğer hastalıklar ise tekil olarak gözlenmiştir. Egzersiz intoleransı, miyalji veya rabdomiyoliz gibi kasla ilişkili semptomlar 8 hastada (%44,4) izlenmiş, 9 hastada (%50,0) kreatin kinaz yüksekliği saptanmıştır. Tüm hastalarda kesin moleküler tanı konulmuş olup, olguların büyük çoğunluğunda hastalığa özgü tedavi veya hedefe yönelik yönetim stratejileri uygulanabilmiştir. Erişkin başlangıçlı KMH’ler belirgin klinik ve genetik heterojenite göstermekte olup sıklıkla özgül olmayan nöromüsküler veya nörolojik bulgularla prezente olmaktadır. Bu bulgular, açıklanamayan multisistem tutulumlu erişkin hastalarda KMH’lerin ayırıcı tanıda düşünülmesi gerektiğini ve doğru tanı ile zamanında tedavi için biyokimyasal ve genetik değerlendirmelerin birlikte kullanılmasının önemini vurgulamaktadır.

Anahtar Kelimeler

• kalıtsal metabolik hastalıklar
• erişkin başlangıçlı
• tanısal gecikme

Inherited Metabolic Disorders Diagnosed in Adulthood: A Single Center Experience

Öz

Inherited metabolic disorders (IMDs) are traditionally considered pediatric-onset conditions; however, an increasing number of patients are diagnosed in adolescence and adulthood, often presenting with heterogeneous and nonspecific clinical manifestations. This study aimed to describe the clinical spectrum, biochemical findings, genetic diagnoses, and management approaches in transition-age and adult patients diagnosed with IMDs. This retrospective analysis included 18 patients diagnosed with IMDs. Patients aged ≥16 years were included and defined as transition-age individuals to account for the overlap between pediatric and adult presentations. Demographic, clinical, biochemical, and genetic data were collected, and treatment strategies were recorded. Diagnostic evaluation was based on disease specific biochemical assays supplemented by molecular genetic testing. The cohort included 10 females and 8 males, with a mean age at diagnosis of 34.2 years (range: 16–61 years). The diagnostic spectrum was heterogeneous, with alkaptonuria (n = 4) as the most frequent diagnosis, followed by glycogen storage disease type V (n = 2), while the remaining disorders were individually rare. Muscle-related symptoms, including exercise intolerance, myalgia, or rhabdomyolysis, were observed in 8 patients (44.4%), and elevated creatine kinase levels were detected in 9 patients (50.0%). A definitive molecular diagnosis was established in all patients, allowing implementation of disease-specific treatment or targeted management strategies in the majority of cases. Adult-onset IMDs show marked clinical and genetic heterogeneity and frequently present with nonspecific neuromuscular or neurological findings. These results highlight the importance of considering IMDs in adult patients with unexplained multisystem involvement and underscore the role of integrated biochemical and genetic evaluation for accurate diagnosis and timely management.

Anahtar Kelimeler

• inherited metabolic disorders
• adult onset
• diagnostic delay

Kaynakça

1. 1. Saudubray JM, Garcia-Cazorla À. Inborn Errors of Metabolism Overview: Pathophysiology, Manifestations, Evaluation, and Management. Pediatr Clin North Am. 2018 Apr;65(2):179-208.
2. 2. Ferreira CR, Rahman S, Keller M, Zschocke J; ICIMD Advisory Group. An international classification of inherited metabolic disorders (ICIMD). J Inherit Metab Dis. 2021 Jan;44(1):164-177.
3. 3. Ferreira EA, Buijs MJN, Wijngaard R, Daams JG, Datema MR, Engelen M, van Karnebeek CDM, Oud MM, Vaz FM, Wamelink MMC, van der Crabben SN, Langeveld M. Inherited metabolic disorders in adults: systematic review on patient characteristics and diagnostic yield of broad sequencing techniques (exome and genome sequencing). Front Neurol. 2023 Jul 25;14:1206106.
4. 4. Sirrs S, Hollak C, Merkel M, Sechi A, Glamuzina E, Janssen MC, Lachmann R, Langendonk J, Scarpelli M, Ben Omran T, Mochel F; SFEIM-A Study Group; Tchan MC. The Frequencies of Different Inborn Errors of Metabolism in Adult Metabolic Centres: Report from the SSIEM Adult Metabolic Physicians Group. JIMD Rep. 2016;27:85-91.
5. 5. van Karnebeek CDM, Wortmann SB, Tarailo-Graovac M, Langeveld M, Ferreira CR, van de Kamp JM, Hollak CE, Wasserman WW, Waterham HR, Wevers RA, Haack TB, Wanders RJA, Boycott KM. The role of the clinician in the multi-omics era: are you ready? J Inherit Metab Dis. 2018 May;41(3):571-582.
6. 6. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-24.
7. 7. Gariani K, Nascimento M, Superti-Furga A, Tran C. Clouds over IMD? Perspectives for inherited metabolic diseases in adults from a retrospective cohort study in two Swiss adult metabolic clinics. Orphanet J Rare Dis. 2020 Aug 18;15(1):210.
8. 8. Vengalil S, Polavarapu K, Preethish-Kumar V, Nashi S, Arunachal G, Chawla T, Bardhan M, Mohan D, Christopher R, Bevinahalli N, Kulanthaivelu K, Nishino I, Faruq M, Nalini A. Mutation Spectrum of Primary Lipid Storage Myopathies. Ann Indian Acad Neurol. 2022 Jan-Feb;25(1):106-113.

9. 9. Ozturk Hişmi, B. (2021). Adult-onset inherited metabolic diseases: A single-center experience. Pamukkale Medical Journal, 14(2), 428–434.
10. 10. Sechi A, Fabbro E, Langeveld M, Tullio A, Lachmann R, Mochel F; SSIEM Adult Physicians Metabolic Group. Education and training in adult metabolic medicine: Results of an international survey. JIMD Rep. 2019 Jun 21;49(1):63-69.
11. 11. Moio MR, Milke JC, Moutapam-Ngamby-Adriaansen Y, Alberti AM, Gernay M, Schütz EA, Schwartz IVD, Maillot F. Diagnosis of Inherited Metabolic Disease in Older Patients: A Systematic Literature Review. J Inherit Metab Dis. 2025 May;48(3):e70038.
12. 12. Sirrs S, Fabbro E, Sechi A; SSIEM Adult Metabolic Medicine Training Competencies Working Group. Training competencies in adult metabolic medicine: A survey of working adult metabolic medicine physicians. JIMD Rep. 2022 Jun 30;63(5):468-474.
13. 13. Mochel F. What can pediatricians learn from adult inherited metabolic diseases? J Inherit Metab Dis. 2024 Sep;47(5):876-884.