Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency

An infant girl with elevated blood lactate, pyruvate, and plasma branched-chain amino acids was diagnosed with dihydrolipoamide dehydrogenase (E3; dihydrolipoamide: NAD+ oxidoreductase, EC 1.8.1.4) deficiency. Activities of the pyruvate dehydrogenase complex and E3 from patient were 26 and 2% of controls in blood lymphocytes, and 11 and 14% in cultured skin fibroblasts, respectively. Western blot analysis demonstrated that the amount of E3 protein in fibroblasts from the patient and her father was about half of controls, while Northern blot analysis showed normal amounts of E3 RNA. DNA sequencing of cloned full-length E3 cDNAs from the patient revealed two mutations in separate alleles. One is a single base insertion of an extra adenine in the last codon of the leader peptide sequence (TAC-->TAAC) leading to a nonsense mutation which results in the premature termination of the precursor E3 polypeptide (Y35X). The other is a missense mutation due to substitution of guanine for adenine, causing an Arg-->Gly substitution at amino acid 460 of the mature protein (R460G) which triggers the loss of E3 activity probably by structural change in the E3 dimer. DNA sequencing of E3 cDNAs from the parents demonstrated that the nonsense mutation was inherited from the father and the missense mutation was inherited from the mother.      

Major depression in panic disorder patients with comorbid social phobia

Rates of depression among panic disorder patients are particularly elevated in patients with comorbid social phobia. However, it is unclear whether this association is specific to social phobia, or whether any comorbid anxiety disorder increases the risk of depression. We assessed 100 panic disorder patients and found a significantly higher incidence of lifetime major depression for panic patients with comorbid social phobia or generalized anxiety disorder (GAD). Panic patients with comorbid social phobia had significantly higher scores on measures of dysfunctional attitudes and lower scores on measures of assertiveness; these variables may mediate the link between social phobia and depression in this population.     

Osteogenesis imperfecta lethal in infancy: Case report and scanning electron microscopic studies of the deciduous teeth

Radiologic evaluation of the skeleton and scanning electron microscopic studies of the teeth were performed on an infant boy with a lethal osteogenesis imperfecta (OI) syndrome who died at 10 mo of pneumonia. The skeletal findings included ribs that were focally expanded by fracture calluses, flat vertebral bodies, and wide limb bones. On fractured tooth surfaces, the enamel and dentin were normal as was the dentin calcification front. Although microscopic abnormalities have been noted in teeth from previously reported infants with lethal OI, a few studies also report infants with normal teeth. These differences in dental findings may indicate heterogeneity in OI lethal in infancy. Results of our study indicate that, until the primary biochemical defects in the OI syndromes are elucidated, examination of teeth from other infants with lethal OI and detailed evaluation of other clinical and skeletal features will aid in delineating heterogeneity and variation in expression in lethal OI.     

Learning disabilities and school problems in a regional cohort of extremely low birth weight (less than 1000 G) children: a comparison with term controls

We compared the prevalence of learning disabilities at age 8 years in a subgroup of 68 of 129 (53%) regional cohort of extremely low birth weight (ELBW) children who were considered "normal" neurologically and intellectually (IQ greater than or equal to 85) with that of 114 term group matched controls (C). Both groups were tested with a battery of psychoeducational measures, and parents and teachers completed questionnaires on the school performance of the children. ELBW children were comparable with C on measures of intelligence (ELBW 101 +/- 8, C 104 +/- 11), language, and academic achievement but fared significantly less well in motor performance (p less than .0001). The prevalence of learning disabilities (by predefined criteria) in ELBW children (26%) was not increased compared with C (19%). However, teachers rated significantly more ELBW children as performing below grade level than were C (31% vs 16%, p less than .05), and by parent report, a higher proportion of ELBW children had received special assistance in school compared with C (37% vs 16%, p less than .001). We conclude that although the prevalence of learning disabilities in normal ELBW children was not different from that in controls, ELBW children did less well and utilized more special resources.     

Recurrent infection stones with apparently negative cultures. The case for blind antibacterial treatment.

Infection stones in the urinary tract are always associated with infection with a urease-producing, urea-splitting organism. The most common of these organisms are easy to culture and identify and can be treated early either with an appropriate antibiotic or with an anti-urease agent. Ureaplasma urealyticum and Corynebacterium urealyticum are urease-producing organisms which are difficult to grow; their presence and effects frequently go undetected and untreated. Other organisms, as yet unknown, may also be involved in the same process. We report the first series of 8 patients with recurrent infection-type stones likely to have been caused by a "hard to grow" organism. Five patients never had a positive culture; in 2 patients 1 of 10 urine cultures grew a coagulase-negative Staphylococcus and in 1 patient the same organism was grown from a stone but never in the urine. The clinical course of all of these patients was significantly improved after blind treatment with antibiotics and in one case with an anti-urease agent.     

Violence in psychiatric wards. Role of the lax milieu

In recent years there has been a marked increase in interest and publications dealing with violence in psychiatric facilities. There is general agreement that the increase in violent behavior is real despite underreporting prior to the late 1970s. The author proposes that the changes in structure and functioning of psychiatric facilities following the Community Mental Health Act of 1963 may be one of the factors responsible for the increase of violent behavior. To test this proposal, Index Medicus was searched for articles on violence in psychiatric facilities from 1935 through 1988. The first articles appeared in 1968. A review of leading textbooks of psychiatry during the same period revealed similar findings. The role of the lax milieu is discussed. It is proposed that the "medical model" as described in this paper be reinstituted in short-stay psychiatric facilities.     

Timing of onset of antidepressant response with fluoxetine treatment

OBJECTIVE: The purpose of this study was to assess the time until onset of antidepressant response with fluoxetine treatment. METHOD: The authors evaluated 182 outpatients with major depression who had a sustained acute response to fluoxetine treatment. The outpatients received 8 weeks of treatment with 20 mg/day of fluoxetine and were assessed biweekly with the 17-item Hamilton Depression Rating Scale. The onset of response was defined as a 30% decrease in score on the Hamilton depression scale that persisted and led to a 50% decrease by week 8. The Kaplan-Meier product limit and Cox regression analysis were used to model the relationship between relevant variables and time until onset of response. RESULTS: The authors found that at weeks 2, 4, and 6, the probabilities of having an onset of response (for responders) were 55.5%, 24.7%, and 9.3%, respectively. The cumulative probabilities of onset of response at each time point were 55.5%, 80.2%, and 89.5%. Neither demographics nor clinical characteristics of depression predicted time until initial response. CONCLUSIONS: These data suggest that more than half of eventual responders to fluoxetine treatment at 8 weeks start to respond by week 2; over 75% start to respond by week 4. Conversely, the lack of onset of response at 4-6 weeks was associated with about a 73%-88% chance that patients would not have an onset of response by 8 weeks.     

Rectus muscle orbital wall fixation: a reversible profound weakening procedure.

INTRODUCTION: Surgical treatment of third nerve palsy, sensory exotropia and strabismus secondary to anomalous innervation of the rectus muscles, frequently require large rectus muscle recessions in an attempt to maintain alignment in the primary position and reduce the effects of misinnervation. The aim of this study was to describe and evaluate the results of inactivation of a rectus muscle by its attachment to the adjacent orbital wall. METHODS: Seven subjects diagnosed with third-nerve palsy (three cases), Duane syndrome (two cases), sensory exotropia (one case), and congenital aberrant innervation of vertical rectus muscles (one case) underwent rectus muscle inactivation by orbital wall fixation. The rectus muscle was disinserted from the globe and reattached to the adjacent orbital periosteum using non-absorbable sutures. This surgery was performed on the lateral rectus muscle in six subjects, and surgery was performed on both ipsilateral vertical rectus muscles in one. RESULTS: Postoperatively four of six patients were aligned within 12 prism diopters of orthotropia in primary position. All patients had improvement of the anomalous head posture. In Duane syndrome, lateral rectus inactivation markedly reduced co-contraction and globe retraction. No overcorrections resulted. CONCLUSION: A rectus muscle may be functionally inactivated when its insertion is attached to the orbital periosteum. Advantages of this procedure over extirpation and free tenotomy include permanent disinsertion of the muscle from globe and reversibility.