Difficulties in diagnostics of urea synthesis cycle disturbance

Abstract

Introduction. Hereditary metabolic diseases include a large group of diseases caused by genetic mutations with a high potential risk of transmitting this disorder to future offspring. Manifesting at any age and accompanied by recurrent and progressive clinical symptoms, some of these mutations become incompatible with life, while most lead to gross violations of the normal physiological process of child development. The paper presents a clinical case of hereditary urea synthesis disorder caused by deficiency of ornithine transcarbamylase of mitochondrial matrix in liver (hyperammonemia type 2) as a result of mutation of the OTC gene (MIM 300461). The disease recessive, linked with the X-chromosome and is associated with a high risk of mortality due to accumulation of toxic concentrations of ammonia. Materials and methods. The boy E., born in 2015. Introduction of protein-based complimentary foods and increase in its portion volume is associated with decrease in appetite, regurgitation, nausea, vomiting, flatulence, dyspepsia appear, and sharp weakness progresses. There is a significant increase in the blood concentration of intracellular liver enzymes. Physical development is slowed due to poor weight gain, and neuropsychiatric development lags significantly. Repeatedly examined in the hospital at the place of residence. Results obtained. A total of 47 genes with mutations causing hereditary diseases with predominant liver damage were studied by mass parallel sequencing. Substitution of c.523G>A (p.Asn175Asp) in the OTC gene in hemizygous state was detected. Clinical diagnosis was established: urea cycle metabolism disorder, hyperammonemia, ornithine transcarbamylase deficiency, E 72.2. Dietary recommendations were given. Carbaglu, Recordati, France at the rate of 100 mg/kg/24 h was prescribed on vital signs. Against the background of the therapy and dietary recommendations the condition of the child had a pronounced positive trend. Conclusions. Since the true incidence of this pathology in Russia has not been established (many cases of metabolic disorders of the urea cycle remain undiagnosed), the presented clinical case will allow clinicians, using modern possibilities of structural and functional analysis of the human genome, to make a timely diagnosis and prescribe adequate therapy, thereby not only prolonging the life of a young patient but also significantly improving its quality.