Founder effects of the homogentisate 1,2-dioxygenase (HGD) gene in a gypsy population and mutation spectrum in the gene among alkaptonuria patients from India.

INTRODUCTION: Alkaptonuria (AKU) is a rare metabolic disease. The global incidence is 1:100,000 to 1:250,000. However, identification of a founder mutation in a gypsy population from India prompted us to study the prevalence of AKU in this population and to do molecular typing in referred cases of AKU from the rest of India. OBJECTIVE: To determine the prevalence of AKU in the gypsy population predominantly residing in the seven districts of Tamil Nadu. To determine the molecular characteristic of AKU cases referred to our clinic from various parts of India. METHOD: Urine spot test to detect homogentisic acid followed by quantitative estimation using high-performance liquid chromatography in 499 participants from the gypsy population and confirming the founder mutation in those with high levels by sequencing. Sequence the homogentisate 1,2-dioxygenase (HGD) gene to identify mutations and variants in 29 AKU non-gypsy cases. RESULTS: The founder mutation was detected in homozygous state in 41/499 AKU-affected individuals of the gypsy community giving a high prevalence of 8.4%. Low back pain, knee pain, and eye and ear pigmentation were the most common symptoms and signs respectively. The commonest mutation identified in the non-gypsy AKU cases was p.Ala122Val. CONCLUSION: High prevalence of AKU in the inbred gypsy population at 8.4% was detected confirming the founder effect. Urine screening provided a cost-effective method to detect the disease early. Mutation spectrum is varied in the rest of the Indian population. This study identified maximum number of mutations in exon 6 of the HGD gene. Key Points • High prevalence (8.4%) of alkaptonuria (AKU) in the gypsy population due to founder mutation in the HGD gene. • Inbreeding exemplifies the founder effects of this rare genetic disorder. • Urinary screening is a cost-effective method in this community for early detection of AKU and intervention. • The mutation spectrum causing AKU is diverse in the rest of the Indian population.

A simplified staging system based on the radiological findings in different stages of ochronotic spondyloarthropathy.

This study describes a group of 26 patients with ochronotic spondyloarthropathy who were on regular treatment and follow-up at a tertiary level hospital and proposes a simplified staging system for ochronotic spondyloarthropathy based on radiographic findings seen in the thoracolumbar spine. This proposed classification makes it easy to identify the stage of the disease and start the appropriate management at an early stage. Four progressive stages are described: an inflammatory stage (stage 1), the stage of early discal calcification (stage 2), the stage of fibrous ankylosis (stage 3), and the stage of bony ankylosis (stage 4). To our knowledge, this is the largest reported series of radiological description of spinal ochronosis, and emphasizes the contribution of the spine radiograph in the diagnosis and staging of the disease.

Idiopathic chondrolysis of the hip: medium- to long-term results.

BACKGROUND: Chondrolysis of the hip secondary to severe trauma, prolonged immobilization and slipped capital femoral epiphysis have been well documented. There have not been many reports, however, of idiopathic chondrolysis of the hip. We here present our experience with 21 hips with an average follow-up of 23.4 months. METHODS: Twenty patients (21 hips), with gross deformities of the hip who presented with fibrous ankylosis were treated over a 23-year period. Average age at presentation was 13 years. None of the patients responded to a trial of conservative treatment (non-steroidal anti-inflammatory medications, traction and physiotherapy.) RESULTS: Most of the preoperative deformities were corrected following arthrotomy, capsulectomy and skeletal traction. However, return of normal hip motion was not seen in any of the patients. Fibrous ankylosis in a functional position was seen to develop in two patients; one patient underwent hip arthrodesis, while another with bilateral involvement underwent excision arthroplasties. CONCLUSIONS: Circumferential capsulectomy with aggressive mobilization of the hip can correct the deformities associated with this condition, although long-term results are uniformly disappointing with regard to return of hip joint motion in cases of late presentation.