Phenotype-genotype correlation and treatment outcomes in mevalonate kinase deficiency: A large Turkish cohort.
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Kaplan Melike Mehveş, Ekici Tekin Zahide, Kılıç Könte Elif, Balık Zeynep, Aydın Tuncay, Çağlayan Şengül, Arık Selen Duygu, Kurt Tuba, Yıldız Çisem, Karalı Yasin, Kışla Ekinci Miray, Çakan Mustafa, Doğantan Şeyda, Kılbaş Gülşah, Bozkaya Yücel Burcu, Tanatar Ayşe, Şener Seher, Esen Esra, Öner Nimet, Köker Oya, Demir Selcan, Sağ Erdal, Demir Yiğit Yasemin, Baba Özge, Kaya Akça Ümmüşen, Taşkın Semanur, Sunar Yayla Emine Nur, Yıldız Mehmet, Gezgin Yıldırım Deniz, Paç Kısaarslan Ayşenur, Kasap Demir Belde, Kalyoncu Mukaddes, Gürgöze Metin Kaya, Yüksel Selçuk, Kılıç Sara Şebnem, Bora Balahan, Sözeri Betül, Aktay Ayaz Nuray, Bilginer Yelda, Kasapçopur Özgür, Özen Seza, Çelikel Acar Banu
Аннотация
METHODS: This retrospective, multicenter cohort study included 107 genetically confirmed MKD patients followed between 2010 and 2024 across 25 pediatric rheumatology centers in Turkey. Demographic characteristics, clinical features, laboratory parameters, genotypic data, and treatment outcomes were recorded and analyzed.
RESULTS: Of the 107 patients, 48 (44.9%) were female. The median age at symptom onset was 7 (3-24) months, and the median age at diagnosis was 71 (27-115) months. The most frequent clinical features included fever in 105 (98.1%) patients, abdominal pain in 92 (86%), arthralgia in 74 (69.2%), diarrhea in 73 (68.2%), lymphadenopathy in 64 (59.8%), vomiting in 52 (48.6%), and oral aphthae in 50 (46.7%). Less frequent findings included pancreatitis in 2 (1.9%), genital aphthae in 2 (1.9%), neurosensory hearing loss in 3 (2.8%), and hidradenitis suppurativa in 1 (0.9%) patients. Amyloidosis and MAS were reported in 4 (3.7%) and 4 (3.7%) patients, respectively. Among the 107 patients, 45 (42%) had a homozygous V377I mutation (Group 1), 28 (26.2%) had a compound heterozygous mutation involving V377I and a non-V377I allele (Group 2), 15 (14%) had two non-V377I alleles (Group 3), and 19 (17.8%) had a single heterozygous mevalonate kinase gene mutation (Group 4). No statistically significant differences were observed between the groups in demographic features, attack characteristics, clinical manifestations, laboratory findings, or treatment outcomes. IL-1 antagonists were the primary therapeutic agents. Anakinra yielded no clinical response in 14 (13.1%), partial response in 17 (15.9%), and complete response in 13 (12.1%) patients. Canakinumab treatment resulted in no response in 2 (1.9%) patients, partial response in 34 (31.8%), and complete response in 56 (52.3%).
CONCLUSIONS: The variability in clinical manifestations and treatment responses across genotypes highlights the complexity and heterogeneity of MKD, suggesting that factors beyond genotype may influence disease expression and therapeutic outcomes. We also confirm that heterozygous individuals may express the disease phenotype.