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Syndromic anophthalmia is studied by performing positional cloning in two unrelated consanguineous families with clinical anophthalmia and variable malformations of the lung, the heart and the diaphragm, as well as mental retardation. STRA6 mutations have defined a pleiotropic malformation syndrome representing the first human phenotype associated with mutations in a gene from the 'STRA' group.

The discovery of a new inherited metabolic disorder, dolichol kinase (DK1) deficiency that is responsible for the final step of the de novo biosynthesis of dolichol phosphate, is described. The results have shown that two homozygous mutations in the human homologue of the yeast DK1 caused a lethal phenotype, with death in early infancy.

Children with mental retardation of unknown origin should be tested for succinic semialdehyde dehydrogenase (SSADH) deficiency. The deficiency is an inherited defect of neurotransmitter metabolism and of 4-hydroxybutyric acid. Researchers assessed the symptoms and histories of 23 children with SSADH deficiency from 20 families. Blood relationships were identified in 39% of the families. Two separate groups of children were identified, one with normal early development and the other with early developmental disorders. There was a high prevalence of motor delay, language delay, lack of muscle tone, and mental delay., Objectives. To further define the clinical spectrum of the disease for pediatric and metabolic specialists, and to suggest that the general pediatrician and pediatric neurologist consider succinic semialdehyde dehydrogenase (SSADH) deficiency in the differential diagnosis of patients with (idiopathic) mental retardation and emphasize the need for accurate, quantitative organic acid analysis in such patients. Patients. The clinical features of 23 patients (20 families) with SSADH deficiency (4-hydroxybutyric aciduria) are presented. The age at diagnosis ranged from 3 months to 25 years in the 11 male and 12 female patients; consanguinity was noted in 39% of families. Outcome Measurements. The following abnormalities were observed (frequency in 23 patients): motor delay, including fine-motor skills, 78%; language delay, 78%; hypotonia, 74%; mental delay, 74%; seizures, 48%; decreased or absent reflexes, 39%; ataxia, 30%; behavioral problems, 30%; hyperkinesis, 30%; neonatal problems, 26%; and electroencephalographic abnormalities, 26%. Associated findings included psychoses, cranial magnetic resonance or computed tomographic abnormalities, and ocular problems in 22% or less of patients. Therapy with vigabatrin proved beneficial to varying degrees in 35% of the patients. Normal early development was noted in 30% of patients. Conclusions. Our data imply that two groups of patients with SSADH deficiency exist, differentiated by the course of early development. Our recommendation would be that accurate, quantitative organic acid analysis in an appropriate specialist laboratory be requested for any patients presenting with two or more features of mental, motor, or language delay and hypotonia of unknown cause. Such analyses are the only definitive way to diagnose SSADH deficiency; the diagnosis can be confirmed by determination of enzyme activity in white cells from whole blood. We think that increased use of organic acid determination will lead to increased diagnosis of SSADH deficiency and a more accurate representation of disease frequency. As additional patients are identified, we should have a better understanding of both the metabolic and clinical profiles of SSADH deficiency. Pediatrics 1997;99:567-574; mental retardation, succinic semialdehyde dehydrogenase deficiency, 4-hydroxybutyric aciduria, hypotonia, ataxia., ABBREVIATIONS. SSADH, succinic semialdehyde dehydrogenase; GABA, y-aminobutyric acid; MRI, magnetic resonance imaging; EEG, electroencephalogram; CT, computed tomography; EMG, electromyography. Succinic semialdehyde dehydrogenase (SSADH, EC 1.2.1.24) deficiency (4-hydroxybutyric aciduria, McKusick 271980) [...]