Table 1 Clinical findings and further investigations in PRPS1 Gln277Pro mutation carriers

Gender

m

f

f

Phenotypic cluster

CMTX5/Arts

DFN2

None

Current age

36

42

66

Age of onset first symptom

Congenital, hearing loss

Congenital, hearing loss

None

Neurological

Mental retardation

(+) progressive aggressive, childish behavior, starting at age 18

-

-

Ataxia (age of onset)

+, 30 years

-

-

Severity of ataxia (SARA score)

14 out of 40

1 out of 40

0 out of 40

Delayed motor development

-

-

-

Loss of deep tendon reflexes

+

-

-

Hearing loss (age of onset)

+, congenital

+, congenital

Optic atrophy (age of onset)

12

--

-

Uric acid overproduction

Gout

-

-

-

Kidney stones

-

-

-

Renal failure

-

-

-

Serum uric acid (ref 3.4-7.0 mg/dl)

4.3 mg/dl

4.4 mg/dl

4.2 mg/dl

Hematopoetic

Recurrent infections

(+), only from age 6 to 8 years

-

-

Anemia

-

-

-

Other

Short stature

-

-

-

Self-injury

-

-

-

Early death

-

-

-

Lab, electrophysiology and MRI investigations

Nerve conduction studies

-Sensory nerve conduction

Sur: no SNAP; Rad: no SNAP

Sur: normal, Rad: normal

n.d.

Sural or radial nerve

-Motor nerve conduction

Tib: borderline MNCV (40 m/s; ref > 40 m/s); Uln: reduced CMAP (2.1 mV; ref: > 4 mV); reduced MNCV (36 m/s; ref: > 50 m/s)

Tib: normal; Uln: normal

Tibial or ulnar nerve

MRI

Mild cerebellar and parietal cortical atrophy

Mild cerebellar and parietal cortical atrophy

n.d.

Serum creatinkinase (ref <180 U/l)

1168 U/l

141U/l

196 U/l

PRS-I enzyme activity (ref 0.41-1.46 nmol/(min.mg protein)

<0.005 nmol/(min.mg protein)

0.1 nmol/(min.mg protein)

1.04 nmol/(min.mg protein)