IntroductionIsovaleric acidemia (IVA, OMIM #243500) is an autosomal recessive metabolic disorder caused by deficiency of isovaleryl-CoA dehydrogenase (IVD) in the leucine catabolic pathway. This enzymatic defect typically leads to the accumulation of alternative metabolites, including isovaleric acid, isovalerylcarnitine (C5), isovalerylglycine (IVG), and 3-hydroxyisovaleric acid, which, subsequently, can result in acute metabolic acidosis and multi-organ dysfunction [1]. The clinical manifestations of IVA are non-specific, and the disorder is generally classified into acute neonatal, chronic intermittent, and asymptomatic forms, according to age at onset and clinical presentation [2]. The acute neonatal form typically presents shortly after birth with feeding difficulties, vomiting, ketoacidosis, and a characteristic “sweaty feet” odor caused by unbound isovaleric acid, which is most noticeable in the patients’ sweat. Besides, laboratory findings often reveal increased anion-gap metabolic acidosis, hyperammonemia, hypo- or hyperglycemia, and ketosis. Unlike other organic acidemias, bone marrow suppression with pancytopenia, neutropenia, and thrombocytopenia is a distinguishing feature of IVA [1]. If not treated promptly, affected infants may develop cerebral edema accompanied by intracranial hemorrhage, consequently leading to coma or death. It is not uncommon that those who survive the neonatal crisis progress to the chronic intermittent form, which, however, is usually diagnosed after the neonatal period. These patients typically present with recurrent, non-specific developmental delay. Episodes are frequently precipitated by upper respiratory infections or ingestion of high-protein diets, manifesting as recurrent vomiting and lethargy, which may further progress to coma, and metabolic acidosis with ketonuria. With increasing age, the frequency of metabolic decompensations generally declines due to fewer infections and reduced protein intake. Without intervention during the neonatal period, survivors are at a significantly increased risk of developmental delay or intellectual disability. Even among patients who receive standardized management, some still exhibit varying degrees of developmental delay or mild-to-severe cognitive impairment, and most display aversion to high-protein foods [3]. According to previous reports, the asymptomatic form is typically identified by newborn screening. Affected individuals may remain free of clinical symptoms throughout life, presenting only with mild-to-moderate elevation of blood C5 and trace amounts of urinary isovalerylglycine [4]. Management usually centers on dietary restriction of leucine, along with glycine and L-carnitine supplementation. Moreover, during acute episodes, correction of metabolic acidosis and hyperammonemia is also essential. With early intervention, neurocognitive outcomes can approximate those of the general population [5].This report describes a pediatric patient with chronic intermittent IVA, in which the genetic analysis identified a previously unreported homozygous IVD variant, c.899_905delinsCCCACAG (p.Asp300_Thr302delinsAlaHisSer). The following summarizes the patient’s diagnostic evaluation, treatment, and follow-up course.