Late-diagnosed phenylketonuria mimicking x-linked adrenoleukodystrophy with heterozygous mutations of the PAH Gene: A case report and literature review

Abstract

Phenylketonuria (PKU) is a prevalent inherited metabolic disorder caused by a phenylalanine hydroxylase (PAH) or tetrahydrobiopterin (BH4) deficiency, which leads to the accumulation of phenylalanine (PHE). High blood levels of PHE have a toxic effect on the brain and are associated with several neurological signs. Most cases of PKU are identified during infancy, and diagnosis of PKU in adult is rare. Here, we describe a 29-year-old patient with progressive dementia and muscular weakness mimicking X-linked adrenoleukodystrophy. Haematological tests revealed high PHE levels (966.67 μmol/ L, normal 20.00-120.00 μmol/L) and his gene test showed compound heterozygosity for c.740 G > T and c.728 G > A of PAH gene mutations, suggesting a diagnosis of PKU. His condition had controlled partly but not significantly improved with appropriate treatment. Our patient is the first case of late-diagnosed PKU with definite heterozygous PAH gene mutations reported in China albeit he had milder symptoms than the previous reported cases around world. Although late-diagnosed PKU is rare, this diagnosis should be considered for patients presenting with leukoencephalopathy accompanied by common neurological signs.

Keywords: Heterozygous mutations; Late diagnosis; Leukoencephalopathy; Phenylketonuria.