Long-term clinical results of the Metasul metal-on-metal total hip arthroplasty: 12.6 years follow-up of 128 primary total hip replacements.

INTRODUCTION: The purpose of the present study is to report the long-term clinical results of an uncemented total hip arthroplasty (THA) using a Metasul metal-on-metal (MoM) 28-mm bearing and to evaluate the long-term serum cobalt levels. METHODS: At an average of 12.6 years following primary THA, we retrospectively reviewed the clinical results of the first 116 consecutive patients (128 THAs) in our institution who underwent 28-mm Metasul MoM THA. Of the 78 patients who were able to visit our outpatient clinic, serum cobalt levels were evaluated. RESULTS: The overall survival rate of the cohort was 96.1% (95% confidence interval [CI], 93.2-99.6), 12.6 years (95% CI, 12.3-12.7 years) following surgery. 3 patients had undergone revision due to aseptic loosening of the stem and 2 patients sustained a periprosthetic fracture. The average modified Harris Hip Score was 90 (72-97) and the average Oxford Hip Score was 56 (48-60), representing both excellent outcome scores. The average serum cobalt of the entire cohort was 20.1 nmol/L (range 8.5-227.7 nmol/L). Serum cobalt levels of patients with a bilateral MoM THA were significantly higher (35.0 nmol/l, p<0.01). No relation between serum cobalt levels, subjective outcome, radiolucent lines on radiographs and survivorship of the implant was noted. CONCLUSIONS: Long-term results of the metasul MoM bearing articulation in THA seem to be excellent, although cobalt serum levels should be monitored closely.

Recessive ITPA mutations cause an early infantile encephalopathy.

OBJECTIVE: To identify the etiology of a novel, heritable encephalopathy in a small group of patients. METHODS: Magnetic resonance imaging (MRI) pattern analysis was used to select patients with the same pattern. Homozygosity mapping and whole exome sequencing (WES) were performed to find the causal gene mutations. RESULTS: Seven patients from 4 families (2 consanguineous) were identified with a similar MRI pattern characterized by T2 signal abnormalities and diffusion restriction in the posterior limb of the internal capsule, often also optic radiation, brainstem tracts, and cerebellar white matter, in combination with delayed myelination and progressive brain atrophy. Patients presented with early infantile onset encephalopathy characterized by progressive microcephaly, seizures, variable cardiac defects, and early death. Metabolic testing was unrevealing. Single nucleotide polymorphism array revealed 1 overlapping homozygous region on chromosome 20 in the consanguineous families. In all patients, WES subsequently revealed recessive predicted loss of function mutations in ITPA, encoding inosine triphosphate pyrophosphatase (ITPase). ITPase activity in patients' erythrocytes and fibroblasts was severely reduced. INTERPRETATION: Until now ITPA variants have only been associated with adverse reactions to specific drugs. This is the first report associating ITPA mutations with a human disorder. ITPase is important in purine metabolism because it removes noncanonical nucleotides from the cellular nucleotide pool. Toxicity of accumulated noncanonical nucleotides, leading to neuronal apoptosis and interference with proteins normally using adenosine triphosphate/guanosine triphosphate, probably explains the disease. This study confirms that combining MRI pattern recognition to define small, homogeneous patient groups with WES is a powerful approach for providing a fast diagnosis in patients with an unclassified genetic encephalopathy.