Sir: Succinic semialdehyde dehydrogenase (SSADH) deficiency is an inborn error of gamma-aminobutyric acid (GABA) metabolism [3] accompanied by urinary excretion of 4-hydroxybutyric (4-HB) acid, a compound with neuropharmacological properties [5]. Patients present with nonprogressive ataxia, hypotonia, psychomotor retardation, hyperactivity, autistic features and/or convulsions [6]. Jaeken and coworkers [2] reported a successful therapeutic trial with the anticonvulsant Vigabatrin in one patient. In a subsequent report by Gibson et al. [1] Vigabatrin therapy was without clinical improvement in another patient. We wish to report our results of Vigabatrin therapy in SSADH deficiency. Our patient was the second child of consanguineous Turkish parents. She showed gross retardation of motor and psychosocial development, hypotonia and ataxia. Hypotonic cerebral palsy was diagnosed. She sat unsupported at 12 months and walked at 27 months. Gait remained broad based and required support. She did not speak nor comprehend speech, could not feed or dress herself and had no control of bladder and bowel. There was little functional use of the hands. Moreover there were autistic features and severe physical restlessness with insomnia. She indulged in repetitive motor activities, wandering aimlessly for hours during the day and night. She required constant supervision, occasionally with restraint. She developed disruptive and aggressive behaviour with explosive outbursts. At 4 years of age grand mal and myoclonic seizure activity were noted, partially controlled by sodium valproate. At 8 years of age atypical absence seizures developed and ethosuccimide therapy was added. However, seizures could not be completely controlled. At 8 years old SSADH deficiency was diagnosed [4, patient 2]. At 12 years of age Vigabatrin therapy was started with increasing doses fi'om 500 to 3500 mg/d. Within 2 weeks of this therapy there was neurological improvement. There was noticeable improvement in locomotion. Her gait became non-atactic and support was no longer required. Sodium valproate and ethosuccimide therapy was discontinued as seizures resolved. Over the next several weeks there was a modest improvement in mental development. Her IQ improved slightly from < 20 to 20-50. She began to develop speech consisting of about one dozen intelligible words. She fed herself, picked up a cup, drank and managed a spoon, dressed and undressed herself with assistance and showed bladder control during the day. She could execute simple orders and began to imitate domestic duties.

ABSTRACT. The effect of Cis-platin on the glomerular data substantiating this statement are scarce. In the present study filtration rate and effective renal plasma flow was deter-we compared, GFR and ERPF of young and adult rats after mined using a radioisotope clearance technique in young (3 various doses of Cis-platin. We also evaluated the renal handling wk old) and adult (more than 12 wk old) rats. Cis-platin of this drug by measuring urinary excretion and renal accumuwas administered intravenously in dosages ranging from lation of Pt.2.5 to 10 mg/kg body weight, either as a single dose or fractionated over 5 consecutive days. Following either dose regimen, identical total doses of Cis-platin caused less MATERIALS AND METHODS severe nephrotoxicity in young rats than in adult ones. In ~~~~r i~~~t~ were carried out using male rats of an outbred adult rats fractionated dosage significantly reduced neph-,istar strain (WU/CPB, TNO Zeist, The Netherlands). The rotoxicit~. This was not observed in young rats-The dif-animals were selected according to BW and age. The young rats ference in nephrotoxicity between young and adult rats was were 3-4 wk of age weighing 50-65 g, the adult rats were more due to the renal handling of Cis-platin. After a single dose than 12 wk of age, weighing 270-340 g. Tap water and food were of 5 and 7.5 mg/kg body weight, platinum concentrations available at libitum.were measured in urine and renal tissue. During the first 2 ~~~~l f~~~t i~~ determination. ~h~ GFR and the ERPF were days after Cis-platin administration, up to 60% of the determined by a plasma clearance technique, as described in amount of ~latinum injected was excreted in the urine of detail elsewhere (12). This method involves iv injection of Cr-5 1 both age groups. There was a marked difference, however, EDTA and 1-125 Iodohippurate (Amersham International, in renal platinum concentration between the two groups-In Amenham, England) and a single timed blood sample collected young rats renal platinum concentration was only 63 and 60 min after the injection. The method allows for repeated use 49% of that in adult rats after 5 and 7.5 mg/kg body in the same animal.weight, respectively. We believe that this is due to the pt determination. The Pt content of urine and renal tissue was comparatively larger renal mass in relation to body weight determined by atomic absorption spectrophotometry a in the young animals. Relatively more renal tissue provides Perkin Elmer 2380 spectrophotometer. The urine samples were at least partial protection against nephrotoxic drugs in analyzed without pretreatment and read against a standard curve these young rats. (Pediatr Res 20: 9-14, 1986) based on aqueous standards. The kidneys were weighed, freeze dried, and digested in 65% HN03 at 200" C in 1.5-2 h. PtAbbreviations standards were added to control kidneys which were similarly treated. The dry residue was then dissolved in 2 ml of distilled BW, body weight water, and analyzed. ERPF, effective renal plasma flow Experimental Protocol. Sin...

We compared the nephrotoxic interaction between cisplatin (CP) and amikacin (AM) in young and adult rats, using different dosage combinations. Following a single i.v. dose of CP, AM was administered s.c. for 14 days. The dose of CP was chosen to cause a 20%-50% fall in the glomerular filtration rate (GFR), while a dose of AM was chosen that had only a minimal effect on GFR. In adult rats, a decrease in GFR to 60% of the control value after CP alone was seriously aggravated by a non-toxic AM course given during 2 weeks after CP. In this combination, the GFR per 100 g body weight was reduced to 30% of control at week 2, which rose to 40% of control at week 15. In young rats, a non-toxic AM course did not aggravate the CP-induced impairment in GFR. However, when the dose of AM was increased to cause a 20% reduction in the GFR, the nephrotoxicity was potentiated. When measured at week 2, the GFR per 100 g body weight was 40% of control after the combined treatment compared with 80% of control after CP alone. As in adult rats, there was only a partial recovery of the GFR. In conclusion, in both adult and young rats, a course of AM following a single injection of CP potentiated CP-induced nephrotoxicity.

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