Characterization of tremor in phenylketonuric patients

Abstract

Tremor of unknown origin is detected in 10-30% of early-treated and in more than 30% late-treated phenylketonuric patients. With the aim of characterizing tremor in phenylketonuria, we carried out a systematic study in 54 patients aged 6 to 37 years. Tremor examination was done by applying the WHIGET Tremor Rating Scale and by accelerometer recording (BYOPAC System MP100WSW). Age at diet onset, IQ test results, concomitant plasma phenylalanine levels and index of dietary control were also studied. Tremor was not observed at rest in any case, but was apparent in 22 patients (40.7%) when carrying out a kinetic task. In 15 patients tremor was also evident during maintenance of a postural task at a frequency ranging between 7.5 and 12.7 Hz. Frequency of tremor was not significantly modified by loading the arms or by increasing muscle contraction. Patients with tremor had a later age at onset of phenylalanine restricted diet (p < 0.001). Other treatment-related variables did not differ between patients with and without tremor. Our results of the neurophysiological examination suggest that tremor in phenylketonuric patients is dependent on a dysfunction of central nervous system networks and may be an index of cerebral damage.

The complete European guidelines on phenylketonuria: diagnosis and treatment

“…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 ]. At present, it is not known how many patients have neurological and psychological problems and which adult PKU patients have a higher risk of these problems.…”

Cerebrospinal fluid biogenic amines depletion and brain atrophy in adult patients with phenylketonuria

“…Adulthood may represent an additionally vulnerable time for PKU individuals, as the compensational mechanisms for Phe accumulation may be reduced by the normal brain aging processes. Correspondingly, reports provide evidence that some adult PKU patients may develop intellectual disability and mild parkinsonian signs …”

Late‐Treated Phenylketonuria and Partial Reversibility of Intellectual Impairment

“…A subsequent report from the same Barcelona hospital presented information on a subset of 11 patients with tremor among 18 adult patients (19–37 years of age) with late‐treated PKU. Of those 11, 8 had been placed on a low‐Phe diet at 0.3–6.75 years of age and had a mean IQ score of 69 (range 50–103; Pérez‐Dueñas et al., 2005). Seven patients without tremor, whose individual scores were not listed, had IQ scores higher by 10 points on average.…”