DNAJC12 Deficiency, an Emerging Condition Picked Up by Newborn Screening: A Case Illustration and a Novel Variant Identified

DNAJC12 deficiency is a recently described inherited metabolic disorder resulting in hyperphenylalaninemia and neurotransmitter deficiency. The effect of treatment on the prevention of neurological manifestations in this newly reported and heterogenous disorder is not fully understood, and the optimal treatment strategy remains to be elucidated. The global or regional incidence of the disease is yet to be estimated. Here, we report the first individual diagnosed with DNAJC12 deficiency in Hong Kong; the condition was picked up by newborn screening due to hyperphenylalaninemia after ruling out phenylalanine hydroxylase deficiency and other tetrahydrobiopterin related disorders. Compound heterozygous variants in the <i>DNAJC12</i> gene were identified, which included a novel missense change and a nonsense pathogenic variant. Treatment with neurotransmitter precursors (tetrahydrobiopterin, levodopa, and oxitriptan) was initiated at four months of age, and dietary protein restriction was started at four years and six months of age. He remains asymptomatic at four and a half years of age, apart from having mildly impaired socio-communication and language development. In this report, we discuss the current diagnostic approach to hyperphenylalaninemia in newborn screening and the uncertainties that exist in the clinical outcome from earlier detection, treatment, and monitoring of DNAJC12-deficiency patients.