Journal of Women's Health Care
Open Access
ISSN: 2167-0420
ISSN: 2167-0420
Maha Alotaibi
King Saud Medical City, Saudi Arabia
Scientific Tracks Abstracts: J Women's Health Care
Aim: Recurrent ketoacidosis and hyperammonemia are two of the symptoms of mitochondrial disorders. We report the case of a girl who presented with recurrent ketoacidosis, hyperlactatemia, and hyperammonemia. Between crises, the patient’s cognitive function is completely normal. Complex III deficiencies are rare, and their phenotypes can vary significantly, even among patients with the same genotype. With this discovery, the differential diagnosis of hyperammonemia broadens and the challenge grows. Methods: An 8-year-old girl, the second child of healthy Yamani consanguineous parents, presented to the emergency room with a one-day history of vomiting, lethargy, tachypnea, and tachycardia; no fever was documented. She has previously been well, with uneventful birth and neonatal periods, and she had normal growth and development prior to the recent crisis with a history of recurring similar metabolic crises occurring more than four times. Laboratory investigations in the last admission showed severe high-anion gap metabolic acidosis (pH 7.13, pCO2 10.6 mmHg, and HCO3 7.2 mmol/L). The ammonia level was 201 mcg/dl, the plasma glucose level was normal, and there was 3+ ketonuria. Lactic acid concentration is 6.1 mmol/L.Whole-exome sequencing (WES) was performed on the parent-offspring trio. The patient was homozygous for the UQCRH c.77T>A p (Leu26*) variant, which results in a premature stop codon within a biologically relevant subunit of mitochondrial complex III. Genetic analyses were performed after obtaining a signed informed consent from the patient’s parent. Results: As no variant which could be clinically relevant to the described phenotype was identified in the exome dataset, the search filters were relaxed and the search was expanded to cover variants in genes with no or only partial experimental evidence for their involvement in human disease, with potential relevance to the described phenotype. A novel homozygous nonsense variant NM_006004.3: c.77T>A p.(Leu26*) in UQCRH gene was detected . This variant is predicted to create a premature stop codon within a biologically relevant subunit of mitochondrial complex III. A recent genetic studies revealed a homozygous deletion mutation in UQCRH (hinge protein), which plays a role in the assembly of Complex III (Vidali et al). The nonsense variant c.77T>A p.(Leu26*) is very rare and was not reported before in Genome Aggregation Database (gnomAD), ClinVar, HGMD, Exome Sequencing Project (ESP), 1000Genome project (1000G) and CentoMD® (latest database available, June 2021). Therefore, and based on the ACMG recommendations, the detected variant was classified as likely affecting protein function (class 2P). Both parents were confirmed heterozygous carriers for this variant. Conclusion: A homozygous UQCRH deletion mutation was first described as a cause of mitochondrial disorder with recurrent episodes of severe lactic acidosis, hyperammonaemia, hypoglycemia, and encephalopathy in two cousins, 8 and 11-year-old boys, born consanguineous with a normal clinical phenotype between crisis and good cognitive function. Our patient has similar clinical findings with the same UQCRH mutation, and this provided a more detailed description of the phenotypic spectrum of the cause of hyperammonemia (Algorithm attached) and Complex III deficiency. In conclusion, our findings show that the homozygous UQCRH pathogenic mutation, as evidenced by the CIII defect in patients with recurrent metabolic crises and one of differential diagnosis of hyperammonemia.
Dr Maha Alotaibi is a champion of genetic disease in ministry of health. She has plenty of researches in genetic and metabolic disorders and Ad-Hoc Reviewer. She is training and teaching the medical students from different medical collages and residents in Riyadh. She also participates as a speaker in international and local conferences.