Spectrum of clinical features and genetic variants in mevalonate kinase (MVK) gene of South Indian families suffering from Hyperimmunoglobulin D Syndrome.

Hyper-IgD syndrome (HIDS, OMIM #260920) is a rare autosomal recessive autoinflammatory disorder caused by pathogenic variants in the mevalonate kinase (MVK) gene. HIDS has an incidence of 1:50,000 to 1:5,000, and is thought to be prevalent mainly in northern Europe. Here, we report a case series of HIDS from India, which includes ten patients from six families who presented with a wide spectrum of clinical features such as recurrent fever, oral ulcers, rash, arthritis, recurrent diarrhea, hepatosplenomegaly, and high immunoglobulin levels. Using whole exome sequencing (WES) and/or Sanger capillary sequencing, we identified five distinct genetic variants in the MVK gene from nine patients belonging to six families. The variants were classified as pathogenic or likely pathogenic as per the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines for annotation of sequence variants. Over 70% of patients in the present study had two recurrent mutations in MVK gene i.e. a nonsynonymous variant p.V377I, popularly known as the 'Dutch mutation', along with a splicing variant c.226+2delT in a compound heterozygous form. Identity by descent analysis in two patients with the recurrent variants identified a 6.7 MB long haplotype suggesting a founder effect in the South Indian population. Our analysis suggests that a limited number of variants account for the majority of the patients with HIDS in South India. This has implications in clinical diagnosis, as well as in the development of cost-effective approaches for genetic diagnosis and screening. To our best knowledge, this is the first and most comprehensive case series of clinically and genetically characterized patients with HIDS from India.

Clinical profile and juvenile arthritis damage index in children with juvenile idiopathic arthritis: A study from a tertiary care center in south India.

AIM: This study was designed to determine the clinical profile of juvenile idiopathic arthritis (JIA) and its morbidity using the juvenile arthritis damage index (JADI) score at a tertiary care center in northern Kerala and to compare with data from India and abroad. METHODS: A hospital-based cross-sectional study was carried out over a period of one and half years from January 2011 to July 2012. Clinical and laboratory profiles and morbidity were assessed. RESULTS: There were 62 children (mean age 8.9 ± 3.8 years) with JIA during this period with a median duration of disease of 24 months (2-151 months). The most common subgroup was polyarticular JIA (n = 26; 41.9%) followed by systemic JIA (sJIA) (n = 20; 32.3%), oligoarticular JIA (n = 15; 24.2%) and enthesitis-related arthritis (n = 1; 1.6%). The most common joints involved at presentation were the knee (38.7%) followed by the ankle (25.8%). Weights and heights were less than the fifth centile in 25.8% and 11.3%, respectively, being most affected in sJIA. The frequencies of articular and extra-articular morbidities were highest in sJIA and showed negative correlation with age at onset and positive correlation with the duration of illness. Macrophage activation syndrome was diagnosed in 50% of sJIA with a mortality of 33.3%. We experienced lower frequency of articular (30.6% vs. 60.7%) and extra-articular damage (24.2% vs. 39.3%), growth failure (19.3% vs. 68.5%) and pubertal delay (4.8% vs. 20.2%) compared to another study from north India. CONCLUSIONS: Our study shows lower frequency of morbidity in JIA; probably related to a better healthcare system facilitating early diagnosis and treatment in this part of the country.