The neurological syndrome of infantile cobalamin deficiency: developmental regression and involuntary movements.

Developmental regression is the presenting symptom of most infants with cobalamin (Vitamin B12) deficiency. We present a report of three infants with cobalamin deficiency in which the infants also developed a movement disorder. In each case the mother was a vegetarian and the infant was exclusively breast-fed. In two of the infants, a striking movement disorder consisting of a combination of tremor and myoclonus particularly involving face, tongue, and pharynx appeared 48 h after the initiation of treatment with intramuscular cobalamin. This was associated with marked changes in plasma amino acid levels. Paradoxically, the onset of the movement disorder coincided with overall neurological improvement. The third infant had a persistent focal tremor, which appeared before the commencement of treatment. The movements slowly abated during a 3-6 week period. The presence of a movement disorder in cobalamin deficiency has received less attention than other features, but in a mild form is probably common. It may offer an early clue to the diagnosis before the onset of profound neurological deterioration. The cause of the severe movement disorder that can appear after treatment is not known.

Clinical, pathological and epidemiological aspects of flood plain staggers, a corynetoxicosis of livestock grazing Agrostis avenacea.

Flood plain staggers, a corynetoxicosis of grazing livestock, occurred on flood plains of the Darling river in northern New South Wales between spring 1990 and autumn 1991, associated with the grazing of Agrostis avenacea with diseased inflorescences. Over this period 1722 cattle, 2466 sheep and 11 horses died on 31 farms. Clinical signs were similar in sheep and cattle, being characterised by intermittent episodes of cerebral convulsion superimposed on varying degrees of cerebellar dysfunction. Pathological changes were variable and non-specific, principally reflecting trauma and the generalised nature of the intoxication.

Long-term neurologic consequences of nutritional vitamin B12 deficiency in infants.

A review of the clinical findings in six infants with nutritional vitamin B12 deficiency seen during the last 10 years was undertaken and an attempt made to obtain long-term neurologic follow-up. There was a consistent clinical pattern in vitamin B12-deficient infants; irritability, anorexia, and failure to thrive were associated with marked developmental regression and poor brain growth. Two of the four patients who qualified for long-term review had a poor intellectual outcome. Although early response to treatment is satisfying, the long-term consequences of nutritional vitamin B12 deficiency in infants emphasize the need for prevention or early recognition of this syndrome.

Kinetic study of catecholamine metabolism in hereditary progressive dystonia.

Kinetics of catecholamine biosynthesis and metabolism have been examined in patients with hereditary progressive dystonia with marked diurnal fluctuation of symptoms (HPD, Segawa's disease). Three patients and a healthy control received an oral load of deuterated tyrosine, and monodeuterium labelled catecholamines and their metabolites in urine and plasma were examined by gas chromatography-mass spectrometry. Patients excreted normal amounts of the primary metabolites of dopamine (dihydroxyphenylacetic acid, homovanillic acid) in urine, suggesting normal rates of dopamine production. However, the biological half-life of dopamine in the patients was reduced to about half that of controls. Noradrenaline biosynthesis and metabolism were normal. Taken together, these results are interpreted to show a reduced biological half-life of dopamine in the brains of these patients, possibly caused by a defect in dopamine storage. Impaired dopamine storage may be the basis of the diurnal fluctuation in symptoms.

Serious neurological complications of measles--a continuing preventable problem.

Eight children who presented to two Sydney children's hospitals in 1984 with the neurological complications of measles infection are described. Six of these children have either died or have serious residual neurological abnormalities. Experience in the United States indicates that such complications of measles can be virtually eliminated by a programme of compulsory immunization of pre-school children.

Phytanic acid oxidase deficiency in childhood.

Tables 2 and 5 summarize the major clinical and biochemical findings in these patients. Cases 1 and 2 resemble clinically the previous cases of children reported as suffering from infantile phytanic acid storage disease, Zellweger's disease, or neonatal adrenoleucodystrophy. Cases 3 and 4 differ strikingly from these and from one another. Numerous questions remain unanswered, but it seems likely that these patients have in common defects in peroxisomal function which are related but not identical. Why some patients with phytanic acid oxidase deficiency do not have significant elevation of serum phytanic acid is not known. These results, however, make it clear that a normal serum phytanic acid level does not exclude phytanic acid oxidase deficiency. In children with a progressive neurological illness, with liver disease, retinal disease, unexplained neuropathy or deafness, detailed studies of fatty acid metabolism are indicated, including lipoproteins, serum phytanic acid, C26:C22 long-chain fatty acid ratios, serum pipecolic acid and phytanic acid oxidase levels. Electron microscopy of liver biopsy specimens should be considered. Phytanic acid oxidase may prove a useful marker for some of these illnesses, and its usefulness could extend to prenatal diagnosis and assist in genetic counselling.

Hereditary motor and sensory neuropathy of neuronal type with onset in early childhood.

Eleven cases of a severe neuropathy with onset in early childhood are described. The condition commences with distal weakness and wasting of the lower limbs and subsequently involves the hands, causing severe paralysis of the hands and feet towards the end of the second decade. Sensory changes are common but are usually only mild. The peripheral nerves are not enlarged. Claw hand, scoliosis and other orthopaedic deformities are seen in the later stages. CSF protein is not elevated and there is only mild slowing of motor conduction velocities. The pathological changes in sural nerve biopsies are those of axonal degeneration affecting myelinated and unmyelinated fibres. Family studies suggested autosomal recessive inheritance in two kindreds and dominant inheritance in another. Five cases were sporadic. The condition is clinically more severe and of earlier onset than hereditary motor and sensory neuropathy (HMSN) type II and differs electrophysiologically and pathologically from Déjerine-Sottas disease.

Visual deterioration as presentation of subacute sclerosing panencephalitis.

A 7-year-old boy presented with deteriorating vision and macular degenerative changes. A month later he had developed unusual behaviour and increasing forgetfulness. An electroencephalogram showing periodic complexes, and high measles complement-fixation titres in the cerebrospinal fluid and blood, confirmed the diagnosis of subacute sclerosing panencephalitis. Four months after the onset of visual symptoms he started having myoclonic jerks.