Sight-Threatening Phenylketonuric Encephalopathy in a Young Adult, Reversed by Diet

Abstract

Phenylketonuria (PKU) leads to severe neurological disorders in childhood, shunned by the diet. The long-term prognosis after diet diversification at adolescence is uncertain. We report a case of cortical blindness in a young patient regressive 1 month after the diet was resumed.Mr M., 25 years old, had PKU detected at birth. He maintained good serum levels of Phenylalanine (Phe) (120-300 μmol/L) during childhood and got a normal intellectual development. During adolescence he diversified his diet but maintained low meat and fish intake; Phe was ~1,200 μmol/L with no symptoms. In 2009, the patient stopped the low-Phe amino acid substitutes due to weariness. On June 27, 2011, he consulted for a decrease of visual acuity progressing for 6 months. Ophthalmologic examination found that visual acuity was 2/10 in two eyes associated to a central visual field defect. The visual evoked potentials were altered. MRI showed bilateral and symmetric occipital FLAIR hyperintensities. On admission in the Nutrional Unit on June 29, 2011, blood pressure was 120/70 mmHg, there was no other neurological abnormality. Phe was at 1,512 μmol/L, and not responsive to BH4. He was then treated with a very low-Phe diet with an amino acid substitute, and he obtained Phe between 120 and 300 μmol/L. Visual acuity was suddenly restored on August 1, 2011, with a dramatic attenuation of the MRI hyperintensities.Our observation shows that the withdrawal of the diet and substitutes exposes to serious neurological complications in adults that may reverse with a fast nutritional support.

The complete European guidelines on phenylketonuria: diagnosis and treatment

“…Some patients who experience suboptimal outcomes and return to diet improve. In adults, the reported neurological complications ( n = 4) [ 66 ] and vision loss ( n = 2) [ 67 , 68 ] all improved or even reversed when Phe-restricted diet with Phe-free L-amino acid supplements was reinstituted [ 66 – 68 ]. In addition Schmidt et al [ 69 ] reported reversible effects on sustained attention and calculation speed in a trial with 15 adults.…”

“…ETPKU adults usually show a clear relationship between concurrent blood Phe concentrations and certain aspects of brain function, brain metabolism and differences in myelination as summarized by van Spronsen et al [ 72 ]. Some adults who have not been treated early and continuously have been reported to develop neurological complications such as leukoencephalopathy, spastic paraparesis, brisk reflexes, tremor, Parkinsonism, psychiatric symptoms ( n = 4) [ 66 ] and vision loss ( n = 2) [ 67 , 68 ]. Tremors have also been detected in ETPKU, although they are more frequent and severe in late treated patients [ 73 ].…”

Le dépistage de la phénylcétonurie en France

“…Initialement, les traitements étaient arrêtés pendant l'enfance ou au début de l'adolescence. L'apparition de complications neurologiques [25,26]…”

La phénylcétonurie

“…En effet, en l'absence de contrôle [43]. Des atteintes neurologiques sévères ont cependant été décrites chez certains patients qui n'avaient plus observé leur régime (avec des taux de Phé plasmatique parfois supérieurs à 1 800 µmol/L [30 mg/ dl]) : perte de la marche, épilepsie et parfois perte de la vision [27]. Ces patients peuvent néanmoins récupérer, le plus souvent totalement, après une remise à un suivi strict du régime alimentaire.…”