Late-onset Presentation Research Articles

Streptococcus pneumoniaeInfections in the Neonate

Streptococcus pneumoniae infections in the neonate (SPIN) are relatively unusual events (1%-11% of neonatal sepsis) but are associated with substantial morbidity and mortality. Previous reports suggest that invasive SPIN is associated with prolonged rupture of membranes, maternal colonization/illness, prematurity, early-onset pneumonia presentation (<72 hours), and high mortality (50%). The aim of this study was to review the current epidemiology and clinical course of SPIN. The US Pediatric Multicenter Pneumococcal Surveillance Group has been prospectively monitoring S pneumoniae infections since 1993 in 8 children's hospitals. For this report, data were gathered retrospectively from the charts of neonates who were 30 days of age and younger and had SPIN from September 1993 to February 2001. All pneumococcal isolates were sent to a central laboratory for serogrouping/typing and susceptibility testing. Twenty-nine cases of SPIN were identified from a total of 4428 episodes of S pneumoniae infection in children. Sixty-six percent were male, and 55% were white; the mean age was 18.1 day (+/-8.2). Ninety percent of infants were >or=38 weeks' gestation. Two mothers had bacterial infections at delivery; 1 had S pneumoniae isolated from both blood and cervix, and 1 had clinical amnionitis. The primary diagnoses in the neonates were bacteremia (8), meningitis (8), bacteremic pneumonia (4), septic arthritis/osteomyelitis (1), and otitis media (8). Thirty percent of infants with invasive SPIN presented with leukopenia/neutropenia, but this did not predict poor outcome. The infecting pneumococcal serogroups were 19 (32%); 9 (18%); 3 and 18 (11% each); 1, 6, and 14 (7% each); and 5 and 12 (3.5% each). Twenty-six percent of invasive neonatal infections were caused by serogroups 1, 3, 5, and 12, which are not contained in the heptavalent pneumococcal vaccine. In contrast, 6% of invasive nonneonatal disease was caused by these same nonvaccine serogroups. Susceptibility testing demonstrated that 21.4% of isolates were penicillin nonsusceptible and 3.6% were ceftriaxone nonsusceptible. Three (14.3%) neonates with invasive SPIN died; all deaths occurred within 36 hours of presentation. Deaths did not appear to be related to pneumococcal serogroup or susceptibilities. Compared with previous studies of neonates with pneumococcal infection, this series showed that infants with SPIN were usually 2 to 3 weeks of age at presentation; likely to be full term; and ill with pneumonia, meningitis, and otitis media. This late-onset presentation was associated with an overall mortality rate of 10.3% (14.3% for invasive disease).

Late-onset presentation of ornithine transcarbamylase deficiency in a young woman with hyperammonemic coma

Ornithine transcarbamylase deficiency (OTCD) is an X-linked inherited disease and the most common inborn error in urea synthesis in human patients. In adult heterozygous patients, OTCD can be responsible for life-threatening hyperammonemic coma. We report the case of a 32-year-old woman admitted to our hospital with seizures after a recent high protein load. Her parents related a history of recurrent episodes of vomiting, meat refusal, lethargy, and convulsions since childhood, and measurement of plasma ammonemia levels was the key to early diagnosis of OTCD. We report the pathophysiologic characteristics, clinical features, clinical course, and differential diagnosis of OTCD and discuss the therapeutic options, including continuous venovenous hemodiafiltration and pharmacologic therapy for reduction of plasma ammonemia levels. A diagnosis of OTCD should be considered in adult nonhepatic patients with hyperammonemic coma, particularly if they have a history of protein avoidance and neurologic symptoms. Early recognition and appropriate treatment are critical to avoid severe brain damage and death. [Ann Emerg Med. 2003;41:104-109.]

A male patient who developed late-onset primary biliary cirrhosis presenting with antinuclear envelope antibodies

A male patient who developed late-onset primary biliary cirrhosis presenting with antinuclear envelope antibodies

Clinical-biochemical correlation in molecularly characterized patients with Niemann-Pick type C

PurposeNiemann-Pick disease type C (NP-C) is an autosomal recessive lipid storage disease manifested by an impairment in cellular cholesterol homeostasis. The clinical phenotype of NP-C is extremely variable, ranging from an acute neonatal form to an adult late-onset presentation. To facilitate phenotype-genotype studies, we have analyzed multiple Israeli NP-C families. MethodsThe severity of the disease was assessed by the age at onset, hepatic involvement, neurological deterioration, and cholesterol esterification studies. Screening of the entire NPC1 coding sequence allowed for molecular characterization and identification of disease causing mutations. ResultsA total of nine NP-C index cases with mainly neurovisceral involvement were characterized. We demonstrated a possible link between the severity of the clinical phenotype and the cholesterol esterification levels in fibroblast cultures following 24 hours of in vitro cholesterol loading. In addition, we identified eight novel mutations in the NPC1 gene. ConclusionsOur results further support the clinical and allelic heterogeneity of NP-C and point to possible association between the clinical and the biochemical phenotype in distinct affected Israeli families.

Late-Onset GM2 gangliosidosis presenting as burning dysesthesias

Two brothers with a painful neuropathy as a component of late-onset GM2 gangliosidosis of the Sandhoff type are presented. A dramatic response of the severe dysesthesias to amitriptyline and gabapentin is described. Symptomatic sensory neuropathy may be a component of late-onset GM2 gangliosidosis.

Clinical characteristics of children with cerebral white matter abnormalities

The rapidly expanding use of magnetic resonance imaging (MRI) in children with neurological impairments of unknown aetiology has revealed a large number of children with abnormalities of the cerebral white matter, some with leukodystrophy-like white matter abnormalities on MRI, but non-progressive in clinical presentation and course. The aim of this study was to investigate the clinical and neuroradiological characteristics of 26 children with white matter abnormalities of unknown origin and to find diagnostic clues or indicators of progressive versus non-progressive disease. The typical child with white matter abnormalities was characterized by onset of symptoms within the first year of life, most often presenting as general developmental delay and hypotonia. Later-appearing signs were spasticity and ataxia and as a rule severe learning and motor disabilities. Serious ophthalmological signs were frequently seen. Perinatal adverse events were rare, infectious aetiologies not indicated but prenatal stigmata relatively common. The clinical course was progressive in 11 children and non-progressive in 15. Late onset presentation was associated with a progressive course whereas prenatal stigmata and asymmetrical white matter lesions only were found in children with a non-progressive disorder. The MRI showed three main patterns: a) a generalized increase of the T2 signal of the white matter in 12 children, b) a bilateral, symmetric but not generalized abnormality in nine and c) asymmetric, focal or multifocal pathology in five. Useful information as to clinical entities and course was obtained from the combined clinical and radiological assessment. A precise nosological diagnosis could be made in six cases. The study showed that white matter abnormalities in children constitute a heterogeneous group of rare and `anonymous' conditions, motivating collaborative studies for further clarification of background and management.

Pretransplantation clinical status and outcome of emergency transplantation for acute liver failure

Emergency transplantation for acute liver failure has a significantly inferior outcome than transplantations performed for elective indications. The severity of the pretransplantation clinical illness in this group will contribute to the reduced patient survival. We have reviewed the outcome of our first 100 consecutive adult patients who received transplants for acute liver failure and have evaluated and determined which recipient clinical parameters present on admission and at transplantation act as risk factors in early posttransplantation outcome. In patients who received transplants for nonacetaminophen-induced liver failure (n = 79), no static variable determinable on admission (including age, sex, year of transplantation, hospital admission to transplantation period, and fulminant or late-onset presentation) other than cause was predictive of 2-month patient survival. Fulminant Wilson's disease and idiosyncratic drug reactions with 2-month survival rates of 100% and 12.5%, respectively, had significantly different outcomes from other causes. By the time of transplantation, of four dynamic variables significant in a univariate analysis (serum creatinine, encephalopathy grade, Apache 111 and organ system failure scores, and P values < .05), only the creatinine level was an independent variable in a stepwise logistic regression for 2-month survival (r = .33). In patients who received transplants for acetaminophen hepatotoxicity (n = 21), overdose to hepatectomy period was the only significant static variable, with no parameter predictive of outcome present on admission.(ABSTRACT TRUNCATED AT 250 WORDS)

Pretransplantation clinical status and outcome of emergency transplantation for acute liver failure

Emergency transplantation for acute liver failure has a significantly inferior outcome than transplantations performed for elective indications. The severity of the pretransplantation clinical illness in this group will contribute to the reduced patient survival. We have reviewed the outcome of our first 100 consecutive adult patients who received transplants for acute liver failure and have evaluated and determined which recipient clinical parameters present on admission and at transplantation act as risk factors in early posttransplantation outcome. In patients who received transplants for nonacetaminophen-induced liver failure (n = 79), no static variable determinable on admission (including age, sex, year of transplantation, hospital admission to transplantation period, and fulminant or late-onset presentation) other than cause was predictive of 2-month patient survival. Fulminant Wilson's disease and idiosyncratic drug reactions with 2-month survival rates of 100% and 12.5%, respectively, had significantly different outcomes from other causes. By the time of transplantation, of four dynamic variables significant in a univariate analysis (serum creatinine, encephalopathy grade, Apache 111 and organ system failure scores, and P values <.05), only the creatinine level was an independent variable in a stepwise logistic regression for 2-month survival ( r = .33). In patients who received transplants for acetaminophen hepatotoxicity (n = 21), overdose to hepatectomy period was the only significant static variable, with no parameter predictive of outcome present on admission. Of two dynamic variables that were significant at transplantation (serum bilirubin and Apache 111 score, P < .05) only the latter parameter was an independent variable in the regression model ( r = .51). Selection of candidates experiencing acute liver failure for transplantation depends on assessment of both the prognosis of the primary hepatic illiness on admission and, for a successful outcome, the clinical status at the time of proposed grafting.

Etiology and Management of Early and Late Peritransplant Infections

AbstractSubfascial peritransplant infection is a life-threatening complication of renal transplantation with multiple etiologies, early or late onset, and subtle or catastrophic presentation. Thirteen such deep space infections were encountered in 160 consecutive transplants followed for up to 4 years. Difficult management decisions were required frequently. Three patients presented with acute peritonitis. In each instancethe source of infection was obscure until abdominal exploration revealed transperitoneal rupture of an infected peritransplant fluid collection. Gray scale ultrasonography and ultrasound guided needle aspiration of fluid collections proved valuable in the clarification of often confusing clinical situations. The transplant was left in situ, with good function and complete wound healing in5 cases. Transplant nephrectomy was required in 8 patients. Three patients died despite transplant nephrectomy and discontinuation of immunosuppression.