Poor Prognosis In Infants Research Articles

Delayed diagnosis of complex glycerol kinase deficiency in a Chinese male infant: a case report

BackgroundXp21 contiguous gene deletion syndrome is a rare genetic metabolic disorder with poor prognosis in infants, involving deletions of one or more genes in Xp21. When deletions of adrenal hypoplasia (AHC), Duchenne muscular dystrophy (DMD), and chronic granulomatosis (CGD) loci are included, complex glycerol kinase deficiency (CGKD) can be diagnosed. We present a case of CGKD that was initially misdiagnosed and died during treatment in our hospital in terms of improving our understanding of the clinical features and diagnosis of this disease, as well as highlighting the need for more precise dosing of corticosteroid replacement therapy.Case presentationA 48-day-old full-term male infant was transferred to our medical center with global growth delay and persistent vomiting. Routine laboratory tests revealed hyperkalemia, hyponatremia, and a high level of creatine kinase. The initial diagnosis was adrenal cortical hyperplasia (ACH), then revised to adrenocortical insufficiency with a normal level of ACTH detected. After supplementing the routine lipid test and urinary glycerol test, CGKD was diagnosed clinically due to positive triglyceridemia and urinary glycerol, and the follow-up gene screening further confirmed the diagnosis. The boy kept thriving after corticosteroid replacement and salt supplementation. While levels of serum ACTH and cortisol decreased and remained low after corticosteroid replacement was administered. The patient died of acute type 2 respiratory failure and hypoglycemia after an acute upper respiratory tract infection, which may be the result of adrenal crisis after infection. Infants with CGKD have a poor prognosis, so physicians should administer regular follow-ups, and parents counseling during treatment to improve the survival of patients.ConclusionsOverall, CGKD, although rare, cannot be easily excluded in children with persistent vomiting. Extensive blood tests can help to detect abnormal indicators. Adrenal crisis needs to be avoided as much as possible during corticosteroid replacement therapy.

Nonimmune hydrops fetalis and congenital disorders of glycosylation: A systematic literature review.

Numerous etiologies may lead to nonimmune hydrops fetalis (NIHF) including congenital disorders of glycosylation (CDG). Recognition of CDG in NIHF is challenging. This study reviews prenatal and neonatal characteristics of CDG presenting with NIHF. A systematic literature search was performed. Thirteen articles met the inclusion criteria. Twenty-one cases with NIHF associated with a CDG were reported. There were 17 live births, three pregnancy terminations, and one fetal demise. Timing of CDG diagnosis was reported mostly postnatally (90%; 10/11). Postnatal genetic testing was reported in 18 patients; three patients were diagnosed by isoelectric focusing of serum transferrin that showed a type 1 pattern. The genes reported for CDG with NIHF for 15 distinct families include: PMM2 in 47% (7/15), ALG9 in 20% (3/15), ALG8 in 13% (2/15), ALG1 in 7% (1/15), MGAT2 in 7% (1/15), and COG6 7% (1/15). In our review, 81% (17/21) reported facial dysmorphism, 52% (11/21) reported CNS abnormalities, most commonly cerebellar atrophy (64%; 7/11), and 38% (8/21) reported cardiovascular abnormalities, most commonly hypertrophic cardiomyopathy (63%; 5/8). Among live births, 71% (12/17) infants died at a median age of 34 days (range 1-185). Thrombocytopenia was reported in 53% (9/17) patients. Of those who survived past the neonatal period, 80% (4/5) had significant reported developmental delays. CDG should be on the differential diagnosis of NIHF in the presence of cerebellar atrophy, hypertrophic cardiomyopathy, or thrombocytopenia. Our review highlights the poor prognosis in infants with NIHF due to CDG and demonstrates the importance of identifying these disorders prenatally to guide providers in their counseling with families regarding pregnancy management. SYNOPSIS: Poor prognosis in fetuses and infants with nonimmune hydrops fetalis due to congenital disorders of glycosylation highlights the importance of prenatal diagnosis of this disorder.

PS-186 Blood Lactate As A Predictive Marker For Neonatal Necrotising Enterocolitis (nec) Severity And Operative Outcomes: Abstract PS-186 Table 1

Background and aims Lactate as a marker for tissue perfusion and hypoxia is increasingly used in routine point-of-care monitoring in critical care. We investigated the association of pre-operative lactate (PreL) with operative outcomes and mortality in neonatal surgical NEC. Methods 25 infants with NEC confirmed on laparotomy at a tertiary surgical centre were retrospectively evaluated. Maximal PreL was categorised as normal ( 5 mmol/L), and correlated to extent of NEC involvement and mortality. Results Median birth gestation and weight were 27weeks (range 23–33) and 1035g (555–2060). Median PreL was 5.1(range 0.6–16.2)mmol/L. Elevated PreL correlated with NEC severity, with predominance of pan-intestinal and multifocal involvement in severe hyperlactaemia (Table 1). Infants with isolated NEC were observed to have normal or moderate-PreL. Moderate to severe PreL was also associated with increased mortality rate and need for further surgery. Conclusions This preliminary study suggests that pre-operative hyperlactaemia and degree of elevation may be associated with a poor prognosis in infants with surgical NEC. Further larger studies may enable better evaluation of its use an adjunctive monitoring or prognostic tool in guiding early neonatal NEC management.

Cytogenetic studies of infant acute lymphoblastic leukemia: poor prognosis of infants with t(4;11) - a report of the Children's Cancer Group.

Infants less than 1 year of age at diagnosis of acute lymphoblastic leukemia (ALL) have a poor prognosis, which has been attributed primarily to a breakpoint in chromosomal band 11q23 or the MLL gene. Most infants with an 11q23 breakpoint have a t(4;11)(q21 ;q23). We studied the cytogenetics of the leukemia cells of 56 infants on CCG-1883, a single-arm clinical treatment protocol for infant ALL. Twenty-one patients had t(4;11)(q21;q23), seven had other rearrangements with breakpoints in 11q23 (other 11q23), 16 had normal chromosomes, two had t(1;19)(q32;p13), one had >50 chromosomes, and nine had non-recurring structural abnormalities. To determine whether there is a difference in outcome for infants with t(4;11), other 11q23 and the remaining patients, we compared event-free survival (EFS) and other clinical and laboratory features of the above infants. Infants without t(4;11) and those with other 11q23 rearrangements had significantly better EFS than those with t(4;11) (P= 0.007 and P= 0.02, respectively). t(4;11) correlated with age less than 6 months and with CD10 negativity, both of which also were poor prognostic indicators. After adjustment for age, there was still a significant difference in EFS between patients with t(4;11) and those with other 1lq23 rearrangements (P=0.02), and between patients with t(4;11) and those without t(4;11) (P=0.04). Among CD10 negative patients, t(4;11) was associated with a worse EFS (P=0.01). Multivariate analysis showed that after adjusting for a variety of clinical and laboratory features, t(4;11) was the most important prognostic factor for poor outcome, and patients with other 11q23 rearrangements had as good an outcome as the remaining patients without t(4;11).

Rearrangement of the MLL gene confers a poor prognosis in childhood acute lymphoblastic leukemia, regardless of presenting age

MLL gene rearrangements are associated with an extremely poor prognosis in infants with acute lymphoblastic leukemia (ALL), but little is known about their clinical significance in older children. Therefore, we studied 45 cases of childhood ALL with abnormalities of chromosome 11q23 for rearrangement of the MLL gene to determine if this feature confers a uniformly poor prognosis. MLL gene rearrangements were detected in all 18 cases with the common t(4;11), t(9;11) or t(11;19) translocations, whereas only 5 of 12 patients with either unbalanced or uncommon balanced translocations demonstrated a rearrangement. Abnormalities of the MLL gene were not detected in any of the 15 cases with a deletion or inversion of the chromosomes 11q23 region. The presence of an MLL rearrangement was significantly associated with age less than 1 year (P < .001), leukocyte count >50 x 10(9)/L (P = .003), and the absence of leukemic cell CD10 expression (P < .001). In a stratified statistical analysis adjusted for age and treatment protocol, MLL gene rearrangement was correlated with an inferior treatment outcome (P = .028). The 4-year event-free survival estimate (+/- SE) was 10% +/- 6.5% for cases with a rearranged MLL gene and 64% +/- 19.2% for other cases. When infants were excluded from the analysis, MLL rearrangement was still significantly associated with a poor outcome (P = .02), and remained so with the exclusion of t(4;11)-positive cases (P = .05). Thus, regardless of presenting age, MLL gene rearrangement identifies a high-risk subgroup of patients who are not likely to be cured with conventional treatment.

11q23/MLL rearrangement confers a poor prognosis in infants with acute lymphoblastic leukemia.

Leukemic cell characteristics were analyzed in infants less than 1 year of age with acute lymphoblastic leukemia (ALL) to determine adverse prognostic factors that might explain the poor prognosis of this group. Treatment outcomes were analyzed according to the presenting clinical and laboratory features of 30 infants treated between May 1979 and April 1993. A stepwise multivariate regression model was used to identify the most important prognostic indicator with respect to event-free survival. Infant ALL cases were characterized by high presenting leukocyte count (median, 87 x 10(9)/L), increased frequency of CNS leukemia (50%), and blast cells with a CD10- phenotype (67%), myeloid-associated antigen expression (48%), and 11q23/MLL rearrangement (68%). The 11q23/MLL involvement was correlated with age less than 6 months, CD10- phenotype, myeloid-associated antigen expression, and high leukocyte count. Although 11q23/MLL involvement, age less than 6 months, myeloid-associated antigen expression, and female sex were each significantly associated with an inferior treatment outcome, only rearranged 11q23/MLL emerged as an independent predictor of prognosis in multivariate analysis (P = .01). Infants with this genetic abnormality had a 4.7-fold (95% confidence interval, 1.3- to 17.0-fold) increased risk in adverse events compared to other infants. The 11q23/MLL involvement of blast cells identifies a major subgroup of infant ALL cases that require an innovative treatment approach. Infants who lack this genetic abnormality have an intermediate prognosis and could be treated accordingly on risk-directed protocols.

Scimitar syndrome in infancy

Objectives. The objectives of this study were to determine the anatomic and physiologic factors most responsible for the severe symptoms and poor prognosis of infants with scimitar syndrome.Background. Whereas the diagnosis of scimitar syndrome is often made incidentally in older children and adults who undergo chest radiography for diverse reasons, infants in whom the diagnosis is made typically present with severe symptoms and have a poor prognosis.Methods. The clinical, catheterization and imaging data of 13 consecutive infants with scimitar syndrome who underwent cardiac catheterization in the 1st 6 months of life were reviewed, with emphasis on the pulmonary artery pressure, pulmonary and cardiovascular anatomy, therapeutic interventions and outcome.Results. Twelve of the 13 infants had pulmonary hypertension at the time of diagnosis. Six patients died despite specific treatment. Eleven of 13 infants had associated cardiac malformations and 9 had large systemic arterial collateral channels to the right lung. Seven patients had anomalies involving the left side of the heart, especially varying degrees of hypoplasia of the left heart or aorta, and six of these patients died. Ten patients underwent surgical or transcatheter therapy in the 1st year of life. Systemic arteries to the right lung were ligated in three patients and occluded by transcatheter embolization in four. Balloon angioplasty was carried out in two patients, one with stenosis of the left-sided pulmonary veins and one with stenosis of the anomalous right pulmonary vein. The latter had placement of a balloon-expandable stent. In both patients, pulmonary vein stenosis progressed. Six patients had surgical repair of associated cardiovascular anomalies, and two required repair of extracardiac congenital anomalies. Occlusion of the anomalous systemic arteries was generally associated with clinical improvement, but congestive heart failure and pulmonary hypertension recurred in those patients with associated cardiovascular anomalies, whose condition subsequently responded after correction of the shunt lesions.Conclusions. The severe symptoms and pulmonary hypertension found in infants with scimitar syndrome have many causes. Anomalous systemic arterial supply, pulmonary vein stenosis and associated cardiovascular anomalies play a significant role, and the ultimate outcome of individual infants depends on the feasibility of treating these anomalies in early infancy.

OUTCOME OF PRETERM INFANTS WITH NEONATAL APNOEIC ATTACKS

The incidence of major disability associated with neonatal apnoeic attacks was studied. The infants had been monitored for apnoea by routine nursing observations and intermittent 24 hr pneumocardiograms. Thirty infants of less than 31 weeks gestation at birth were seen between 2 and 4 years of age. Full physical and ophthalmological examinations were carried out as well as audiometry and Griffiths developmental assessment. The infants were divided into three groups according to the severity of the apnoea: Group I, no apnoea (15 infants); Group II, moderate apnoea (attacks of 20-59 seconds duration) (8 infants); Group III, severe apnoea (10 episodes in 24 hrs, an attack longer than 60 seconds or those requiring ventilation) (17 infants). The results of physical examinations were all normal. No overt defect of visual acuity was found but further fundal examination is being carried out. There was one case of sensorineural deafness in Group I. Developmental quotients (DQ) of the infants in the three groups showed there were no statistically significant differences: Group I, median DQ96; Group II, median DQ 102; Group III, median DQ 91. The result of this study suggests that recurrent or severe apnoeic attacks do not imply a poor prognosis in infants with no other serious neonatal problems.

Infections in hypothermic infants younger than 3 months old.

Hypothermia in infants is associated with considerable morbidity and mortality. Infection is thought to occur frequently and to carry a poor prognosis in infants with hypothermia. The medical records of 51 infants less than 3 months of age hospitalized from 1976 through 1981 with rectal temperatures of 34 degrees C or less were reviewed. Infections were diagnosed in 27 of the 51 infants. Infections were associated significantly with the presence of bradycardia, anemia, abnormal leukocyte counts, abnormal serum glucose levels, and uremia, especially if two or more of these variables were present. Morbidity and mortality were higher among infected than among noninfected infants. No rapid reliable indicators for the presence or absence of infection in an individual infant with hypothermia were found despite the differences noted between the two groups. Until new techniques for the detection of bacterial infections became available, we suggest that antibiotics be given to all infants younger than 3 months of age with hypothermia on admission to the hospital.

Coxsackie A9 focal encephalitis associated with acute infantile hemiplegia and porencephaly

The factors underlying acute infantile hemiplegia are seldom identified. Coxsackie A9 focal encephalitis was documented for the first time in a 3-month-old infant with fever, hemiconvulsions, and hemiplegia followed by a static motor deficit and epilepsy. It has been suggested that the acute infantile hemiplegia associated with encephalitis results from an arteritis or venous sinus thrombosis with subsequent cerebral infarction. However, this was not observed in our patient. Rather, a series of brain scans, computerized tomograms, and a cerebral angiogram clearly documented the evolution of a focal necrotizing encephaloclastic process resulting in a porencephalic cyst. Serial cerebrospinal fluid viral cultures were necessary to isolate the etiologic agent (tcoxsackie A9). The infant did not have a neutralizing antibody response to the infecting viral agent despite an apparently intact immune system, which possibly may be explained by the developed of immune tolerance or an insufficient amount of infecting viral antigen. This emphasizes that serologic studies alone may not be adequate to document an acute central nervous system viral infection. This patient also typifies the poor prognosis in infants presenting with acute hemiplegia, fever, and convulsions in the absence of cerebrovascular occlusion.