P2.237: Late Diagnosis of Metabolic Disorder in the Setting of Acute Illness

Introduction: Inborn errors of metabolism include a wide variety of conditions associated with disruptions in metabolic pathways. Beta-ketothiolase deficiency (BKD) is a metabolic disorder that typically presents before 2 years of age. We report an unusual presentation of BKD that presented later in childhood as encephalopathy during admission for perforated appendicitis.

Case Description: A developmentally normal 7-year-old male with no significant past medical history presented to the Emergency Department with a 3-week history of peri-umbilical pain. His initial labs were notable for hypoglycemic ketoacidosis thought to be secondary to his anorexia. He was diagnosed with complicated perforated appendicitis with subsequent IR drainage and initiation of ceftriaxone and metronidazole. Within 24 hours, he developed hyperreflexia. He was transferred to the PICU where he developed hypotonia, choreiform movements, and dysarthric speech. Workup included video EEG, lumbar puncture, and nerve conduction studies, all of which were unrevealing. MRI brain and spine revealed symmetric punctate foci of diffusion restriction and T2 prolongation of the posterior globi pallidi concerning for toxic material exposure or viral infection. Initial suspicion was for metronidazole-induced encephalopathy. However, due to lack of response post-drug cessation the differential diagnosis was expanded to include metabolic disorders.
The patient was started on a mitochondrial cocktail, thiamine, and dextrose. Speech, mentation, and choreiform movements improved throughout admission and he was able to be discharged home. After discharge, he was diagnosed with BKD at an outpatient Neurology follow-up visit via genetic testing. He continued to improve outpatient and is doing well on levocarnitine.

Discussion: BKD is typically diagnosed via newborn screening with elevated serum acylcarnitine profile. The typical presentation of BKD is episodic ketoacidosis during periods of poor oral intake. Normo- or hypo-glycemic ketoacidosis can be suggestive of endocrine disorders or metabolic disorders, including organic acidurias such as BKD, and should be thoroughly evaluated in children.
Although BKD typically presents within the first 2 years of life, it may not be diagnosed until later in life after periods of prolonged fasting. Certain BKD mutations can present asymptomatically at birth, leading to these cases going undetected in the early years of life. BKD can be missed on newborn screening and should still be considered even in patients with negative newborn screens. Delays in diagnosis of BKD can lead to outcomes including encephalopathy, neurological impairment, and even death.

Conclusion: This case report highlights an unusual case of BKD diagnosed in childhood, explores the impact of delayed diagnosis of an inborn error of metabolism, and presents symptoms of BKD that manifest in childhood. In acute care settings, physicians should include metabolic conditions on the differential for patients who present with acute MRI and neurological changes during periods of high stress or illness.