Treatment resistant hyperammonemia in beta ketothiolase deficiency in an infant: A case report

Beta-keto thiolase deficiency, also known as Alpha-methyl acetoacetic aciduria, T2 deficiency, 2-methyl acetoacetyl-CoA thiolase (MAT) deficiency, is a rare genetic organic aciduria caused by mitochondrial enzyme acetoacetyl-CoA thiolase (T2) deficiency that affects both ketone body metabolism and the catabolism of isoleucine, both of which are crucial for energy production. A 12-month-old baby girl, meeting typical developmental milestones, presented with a wide range of symptoms, including altered sensorium, fever, rapid breathing, lethargy, and irritability over three days. History revealed consanguineous marriage between her parents and the death of an undiagnosed sibling. Physical examination showed a lethargic, pale, and dehydrated child with tachypnea and characteristic acidotic breath. Laboratory tests revealed anemia, severe metabolic acidosis with a high anion gap, hyperkalemia, and high serum ammonia. Urine organic acids analysis showed elevated levels of 2-methyl-3-hydroxybutyric acid and 3-hydroxybutyric acid, which confirmed the diagnosis of beta-keto thiolase deficiency.Genetic testing further supported this diagnosis by identifying an ANTXR2 gene mutation. A supportive treatment plan included adequate fluid to correct dehydration, bicarbonate to correct metabolic acidosis, and sodium benzoate to reduce ammonia levels. The patient was also advised to follow a protein-restricted diet and take biotin and sodium bicarbonate in the long run to manage the condition. With treatment, the patient's condition improved, and she began to achieve developmental milestones. However, the crisis affected her speech, and speech therapy was recommended. This case report highlights the importance of early neonatal screening in Pakistan, particularly in light of the increasing rate of consanguineous marriages and the rising incidence of organic acidemias, which can lead to early diagnosis and prompt management. • Beta-keto thiolase deficiency is a rare metabolic disorder in children. • Caused by mutations in the ACAT1 gene, it disrupts isoleucine and ketone body metabolism. • Case of a infant girl with treatment-resistant hyperammonemia, later diagnosed with beta-keto thiolase deficiency.