Heterogeneous clinical spectrum of DNAJC12-deficient hyperphenylalaninemia: from attention deficit to severe dystonia and intellectual disability

Hyperphenylalaninemia is one of the most common inherited metabolic diseases diagnosed in the newborn screening and until now follow-up investigation included differential diagnosis of phenylketonuria (PKU) and tetrahydrobiopterin (BH4) deficiency. With the description of patients with biallelic variants in co-chaperone DNAJC12 (van Spronsen et al 2017), the paradigm of hyperphenylalaninemia needs reconsideration. DNAJC12-deficient patients may present initially without any symptoms, with only mild attention deficit or with a severe intellectual disability, and need immediate and appropriate treatment (BH4, l-dopa/Carbidopa and 5-hydroxytryptophan). Thus, every newborn with hyperphenylalaninemia, in which PKU and BH4 deficiency were excluded need to be tested for DNAJC12 variants. (By Prof. Dr. Beat Thöny, http://jmg.bmj.com/content/early/2017/08/09/jmedgenet-2017-104875 )