PC2149: One Enzyme, Two Generations: The Impact of Phenylketonuria and Poverty

Introduction: Phenylketonuria is an autosomal recessive phenylalanine hydroxylase deficiency, causing buildup of phenylalanine (Phe). The mainstay treatment is lifelong low-Phe diet although adherence often drops in young adulthood. In gestational parents, poor control of Phe levels not only affects their neurological status, but also impacts the next generation via maternal PKU syndrome.

Case Description: A 5-week-old male infant who presented to the ED with seizure-like activity, described as bilateral jerking of the head and arms without cyanosis or post-ictal period. The patient was noted to have microcephaly (0.08th percentile) with hypotonia and a systolic murmur. The newborn screen was normal. On EEG, no epileptiform activity noted; the movements were deemed benign myoclonus of infancy. Further history revealed that the patient’s mother has phenylketonuria (PKU) and the child had been diagnosed with an ASD after birth. Due to this history and constellation of microcephaly, hypotonia, and cardiac abnormalities, the patient was diagnosed with maternal PKU syndrome.

Throughout the pregnancy, diagnosed in the first trimester, the mother’s Phe levels were >500mg/dL. The parent of the patient is a 37-year-old woman with a history of PKU who had already experienced a TIA and periodically experienced headaches and “brain fog.” She worked temp jobs without health insurance, buying high-Phe foods near her workplaces. Due to housing insecurity, her family was living in a motel without a full kitchen. The patient’s mother endorsed motivation to follow up, attending dietician and social-work meetings with her son at Genetics clinic, but was lost to follow up.

Discussion: Maternal PKU syndrome is a constellation of symptoms that can include congenital heart disease, developmental delay, microcephaly, and elevated seizure risk. For gestational parents with PKU, control of Phe levels ( < 6mg/dl) is recommended for at least 3 months prior to conception since the teratogenic effects of Phe are most potent in the first trimester. Inconsistent adherence to the low-Phe diet often begins in adolescence, driven by social pressures, changes in material support, and the restrictive nature of the diet. The patient’s mother was diagnosed at her newborn screen, started a low Phe diet, but stopped at age 10. High Phe levels lead to neurological/psychiatric sequalae including depression and issues with information processing, posing barriers for patient insight and adherence. Early diagnosis and follow up with a multidisciplinary clinic familiar with PKU are vital to long term management, but a dearth of wider social safety nets guaranteeing housing and food security poses steep challenges to optimal care.

Conclusion: A 5-week-old male infant of a mother with PKU presented with spasm was found to have microcephaly, hypotonia, and ASD on exam, diagnosed with maternal PKU syndrome, stemming from the neuropsychiatric sequelae of inadequate PKU management and the social determinants of health affecting both mother and child.