Gwilym Hosking

Biotin-responsive alopecia and developmental regression.

A 10-month-old boy presented with dermatitis and alopecia and became severely hypotonic. Screening for urinary organic acids revealed a large quantity of 3-hydroxyisovaleric acid and raised levels of beta-methylcrotonylglycine and 3-hydroxypropionate. Activities of propionyl CoA carboxylase, beta-methylcrotonyl CoA carboxylase, and pyruvate carboxylase in cultured fibroblasts were normal. Treatment with oral biotin resulted in a dramatic clinical improvement, which might therefore suggest a defect in biotin absorption or transport.

Urinary sediment dolichol excretion in patients with Batten disease and other neurodegenerative and storage disorders.

ABSTRACT: Nonesterified dolichols have been measured in the urinary sediment of 20 patients with the late infantile and juvenile forms of neuronal ceroid lipofuscinosis (Batten disease), in 15 patients with other storage and neurodegenerative disorders and in 10 control subjects. Dolichols were measured by a high performance liquid chromatographic method and were related to urinary creatinine concentration. The levels of dolichols in Batten disease were not significantly elevated when compared to the normal subjects or to patients with other neurodegenerative disorders. The highest levels seen were in two patients with mucopolysaccharidosis types II and IV, respectively. Measurement of dolichols in urinary sediment is of little value in the diagnosis of Batten disease or in furthering our understanding of the underlying primary defect.

Biochemical investigations on a patient with a defect in cytosolic acetoacetyl-CoA thiolase, associated with mental retardation

A severely mentally retarded boy with two normal siblings was persistently found to excrete elevated amounts of 3-hydroxybutyrate and acetoacetate. Enzyme analysis in cultured fibroblasts revealed a probable deficiency in cytosolic acetoacetyl-CoA thiolase which was about half the control activity with normal mitochondrial thiolase activities. Treatment with reduced dietary fat was initiated and a rapid reduction of the ketosis to biochemical normality was demonstrated. Shortly after initiating dietary treatment he presented with severe gastrointestinal problems and the histological features of colitis cystica superficialis. This appeared to respond to intravenous hydrocortisone therapy with an apparent complete recovery.

Juvenile neuronal ceroid-lipofuscinosis : developmental progress after supplementation with polyunsaturated fatty acids

Six patients with juvenile neuronal ceroid‐lipofuscinosis (NCL) who were demonstrated to have abnormally low levels of membrane phospholipids were treated by dietary supplementation with polyunsaturated fatty acids (PUFAs) for periods ranging from 4 years 10 months to 7 years 3 months. Annual evaluations of intelligence and fine motor ability were undertaken while on supplementation. Mental development remained stable in most subjects throughout this period; fine motor function and vision were stable in the two youngest subjects only. These data suggest that PUFA supplementation may arrest the natural course of juvenile NCL if treatment is started early. A larger, multicenter, controlled trial is warranted.

Molybdenum Co‐factor Deficiency: an Easily Missed Inborn Eror of Metaboism

A female patient is described with combined deficiency of sulphite, zanthine and aldehyde oxidase. She presented at the age of four weeks with intractable seizures. Initially the diagnosis was suspected because of a very low serum urate: level (23 μmol/l‐1). This condition can be easily missed and it is proposed that measurement of serum urate be included in the metabolic assessment of neonates with unexplained seizures and developmental delay.

Lipid Abnormalities in Serum in Batten's Disease

two patient registers and conducted computer searches at North Dakota’s comprehensive diagnostic center and the state’s institution for developmentally disabled persons in an attempt to identify patients with co-existing tuberous sclerosis and PDD. We identified three adults and one child with tuberous sclerosis who met criteria for PDD (Table I). From our PDD registers and the patient register of the state’s clinical genetics program we identifed 12 patients in the state with tuberous sclerosis; a prevalence of I 84 per 100,000. Our estimate of the prevalence of PDD was 3.3 per 10,000. The estimated prevalence of co-occurrence of these two conditions (given random assortment and the above prevalence estimates) would be 6.07 x lo’, or approximately six cases of co-existing tuberous sclerosis and PDD per billion. Thus it would be extremely unlikely that we could identify four patients with tuberous sclerosis and PDD in a state with 652,695 residents unless there is a link between the two disorders. For all three of our adult patients, by history, the onset of autism was before two years of age, and all three continue to meet criteria for autism. These findings conflict with Creak’s contention that symptoms common to the two disorders occur for only a short period. It remains unclear why the genetic literature has not generally reported PDD as a clinical manifestation of tuberous sclerosis. WAYNE FISHER, PH.D.* JACOB KERBESHIAN, M.D.? LARRY BURD, M.S.

Lipid abnormalities in Batten's disease

PAUL KOLSTOE, M.A.* *Grafton State School, Grafton, ND 58237 t University of North Dakota School of Medicine, Grand Forks’ ND 58202

PERONEAL MUSCULAR ATROPHY

Medical Center, Rehabilitation Hospital, Grand Forks, ND 58202

A biochemical study on mothers of children with congenital neurodevelopmental abnormalities

Juvenile neuronal ceroid tipofuscinosis (JNCL, Battens Disease, McKusick 20420) is one of a group of severe neurodegenerative disorders, the biochemical basis of which has not yet been established, and for which there is no treatment. Abnormalities have been described which have not conclusively been shown to relate to the primary defect. These include intracellular accumulation of dolichol, an important co-factor in protein glycosylation (Ng Ying Kin et al., 1983; Paton and Poulos, 1984; Bennett et al., 1985) and a deficiency in cellular peroxidation (EgershorJensen and Clausen, 1983). It remains possible that both of these abnormalities are secondary to the basic lesion. We have recently shown a marked reduction in fasting serum pre-[~-lipoprotein (very low density lipoprotein, VLDL) in a number of patients with JNCL and lipid abnormalities in postmortem liver from a single patient (Bennett et al., 1986). We present here the results of further laboratory investigations on living JNCL patients and tissue results from an additional patient at postmortem.

Commonwealth association for mental handicap and developmental disabilities.

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