A CASE REPORT ON PHENYLKETONURIA: EARLY INTERVENTION AND TREATMENT

Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine metabolism, most commonly caused by deficiency of phenylalanine hydroxylase (PAH), the hepatic enzyme that converts phenylalanine (Phe) to tyrosine. Untreated or inadequately treated PAH deficiency results in persistent elevation of blood and brain Phe and can cause neurocognitive impairment, developmental delay, seizures, behavioural abnormalities and psychiatric manifestations. [1-4] We report an 8-year-old male child, second-born to non-consanguineous parents,who presented with hyperactivity, speech delay and behavioural problems. The child had an abnormal urine odour and dysmorphic features including triangular facies, blond hair, low-set ears, long pointed nose, hypopigmented eyes and prominent columella.Developmental assessment demonstrated significant global developmental delay. Psychological assessment showed features of combined-type attention-deficit/hyperactivity disorder (ADHD), with oppositional defiant and conduct features. In view of the behavioural phenotype, developmental delay, hypopigmentation and abnormal urine odour, a metabolic disorder was suspected. Serum amino-acid analysis demonstrated markedly elevated phenylalanine,and whole exome sequencing identified a pathogenic PAH variant consistent with autosomal-recessive PAH deficiency. MRI brain demonstrated abnormalities involving the periventricular white matter, posterior fossa, pons and putamina, with thinning of the corpus callosum. The child was managed through a multidisciplinary approach involving a pediatrician, metabolic/dietetic team,speech therapist,occupational therapist,special educator, ophthalmologist and geneticist. Treatment included lifelong phenylalanine-restricted dietary therapy, rehabilitation and behavioural interventions.