Apparent genotype–phenotype correlation in childhood,adolescent, and adult Chediak‐Higashi syndrome

Chediak‐Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by severe immunologic defects, reduced pigmentation, bleeding tendency, and progressive neurological dysfunction. Most patients present in early childhood and die unless treated by bone marrow transplantation. About 10–15% of patients exhibit a much milder clinical phenotype and survive to adulthood, but develop progressive and often fatal neurological dysfunction. Very rare patients exhibit an intermediate adolescent CHS phenotype, presenting with severe infections in early childhood, but a milder course by adolescence, with no accelerated phase. Here, we describe the organization and genomic DNA sequence of the CHS1 gene and mutation analysis of 21 unrelated patients with the childhood, adolescent, and adult forms of CHS. In patients with severe childhood CHS, we found only functionally null mutant CHS1 alleles, whereas in patients with the adolescent and adult forms of CHS we also found missense mutant alleles that likely encode CHS1 polypeptides with partial function. Together, these results suggest an allelic genotype–phenotype relationship among the various clinical forms of CHS. © 2002 Wiley‐Liss, Inc.     

Familial juvenile hypertrophy of the breast.

OBJECTIVE: Juvenile (virginal) hypertrophy of the breast (JHB) is a relatively rare condition leading to gigantomastia in peripubertal females. The pathology is limited usually to the breast, with otherwise normal growth and development and without any other deformities. The rapid growth of the breast (bilateral or unilateral) in adolescent girls leads to significant physical and psychological difficulties. This gigantomastia is treated surgically by breast reduction or mastectomy and its modification. Familial JHB was described only once in the literature, and its etiology is unknown. RESULTS: We report here on a familial pattern of juvenile hypertrophy of the breast accompanied by congenital anonychia. To the best of our knowledge, this is the first report of such a presentation. Our study dealt with four members of the same family, related through their fathers, enduring congenital anonychia of hands and feet with no functional limitation and who showed rapid uncontrolled breast enlargement in prepubertal age. This was severe enough to cause the curtailment of their social activity and cessation of schooling. The mothers of all four patients had normal breasts and nails, whereas their fathers had anonychia. The genetic basis for the association between the two clinical findings is yet to be determined. CONCLUSION: The four girls underwent breast reduction surgery.     

The efficacy and safety of early supplementation of iron polymaltose complex in preterm infants

The purpose of this study was to examine the efficacy and safety of early nonionic iron supplementation in preterm infants. Infants with gestational age < or = 32 weeks who were fed enriched human milk were assigned concurrently to receive 5 mg/kg/d enteral iron polymaltose complex (IPC) at 2 or 4 weeks of age. The levels of hemoglobin, reticulocytes, serum iron, ferritin, and soluble transferrin receptor were recorded at 2, 4, and 8 weeks of age. The incidence of morbidities associated with prematurity and the need for red blood cell transfusions (RBCTs) were recorded. The 2-week group (n = 32) had a better iron status than the 4-week group (n = 36) at 4 weeks and at 8 weeks of age. The incidence of morbidities associated with prematurity was not different among the groups ( P = 0.26). RBCT was required in one infants of the 2-week group and in 10 infants in the 4-week group ( P = 0.045). The number needed to treat to prevent one RBCT was five. Supplementation of 5 mg/kg/d enteral IPC to preterm infants fed enriched human milk as early as 2 weeks of age was more beneficial to iron status than at 4 weeks of age, and was associated with decreased need for RBCTs and no increase in the incidence of morbidities associated with prematurity.     

The prevention and treatment of perinatal sepsis in a neonatal intensive care unit

We report our experience with 345 premature infants weighing less than 1,500 g admitted to the neonatal intensive care unit during 1990–1993. The improved survival of the very-low-birth-weight patients was related mainly to the routine use of surfactant in the treatment of respiratory distress. In addition, as a result of several preventive precautions, early diagnosis, and appropriate antimicrobial therapy, a decrease in neonatal sepsis was observed. The decrease in the ratio between the number of septic episodes to the number of septic patients is another indication of the efficacy of our current preventive and therapeutic protocols. Correspondence to: S. Katz     

Pre-term delivery,optimism and initial personal growth as predictors of mothers’ long-term personal growth

Introduction: Positive outcomes in the aftermath of childbirth have increasingly been studied in the last decade. However, most of the studies concentrate on short-term outcomes. The current study examined the perceived personal growth of mothers four years after childbirth, investigating the contribution of the event characteristics (full-term/pre-term birth), internal resources (optimism, self-esteem) and personal growth as measured one year after the birth.

Methods: Mothers (n=259) participated in the study by completing a set of self-report questionnaires one and four years following the birth of their child/ren.

Results: Personal growth after four years was found to be higher among mothers of pre-terms than of full-terms, and higher four years after the birth than it had been three years earlier. Furthermore, regression analysis indicated the significant contributions of being a mother to pre-term baby/ies, optimism and personal growth one year after the birth to women’s personal growth three years later.

Discussion: The results highlight the potential long-term effects of giving birth to a pre-term baby on personal growth, as well as the contribution of optimism as an important internal resource. They also indicate the development of personal growth over time. Explanations for the findings are offered and their practical implications are discussed.     

Serum amyloid A protein is a useful inflammatory marker during late-onset sepsis in preterm infants

BACKGROUND: Few studies demonstrated that serum amyloid A (SAA), a non-specific acute-phase reactant, could be used as a reliable early marker for the diagnosis of late-onset sepsis (LOS). OBJECTIVES: To evaluate the diagnostic value and the dynamics of SAA levels during the course of LOS and to compare it to those of other inflammatory markers. METHODS: Levels of SAA, C-reactive protein (CRP) and IL-6 together with clinical variables, biochemical parameters and cultures retrieved from all preterm infants suspected of LOS were checked at the first suspicion of sepsis and after 8, 24, 48 and 72 h. Results were compared to healthy, matched infants. RESULTS: One hundred and sixteen infants were included in the study, 38 in the sepsis and 78 in the non-sepsis group. High levels of SAA were observed at sepsis onset, with a gradual decline thereafter, while CRP levels increased only at 24 h after sepsis onset. In the sepsis group, levels of SAA returned faster to baseline than CRP levels. Receiver-operating characteristic analysis values revealed that SAA at 10 mug/ml had the highest sensitivity at 0, 8 and 24 h after sepsis onset (95, 100 and 97%, respectively) and a negative predictive value (97, 100 and 98%, respectively). CONCLUSIONS: SAA is an accurate acute-phase protein during LOS in preterm infants. Quick and reliable SAA kits can make this marker a useful tool in LOS in preterm infants.     

The prognostic virtue of inflammatory markers during late-onset sepsis in preterm infants

AIM: Late-onset sepsis (occurring after the first three days of life) is a serious complication in preterm infants. In order to assess the possible prognostic virtues of the acute phase inflammatory response in the disease, we compared the inflammatory response of preterm infants who died within 72 hours (h) (fulminant sepsis) to infants who recovered from the disease (non-fulminant sepsis). METHODS: Of 42 preterm infants that were evaluated: 10 had fulminant sepsis and 32 non-fulminant sepsis. Acute phase inflammatory response markers-C-reactive protein (CRP), serum amyloid A (SAA), interleukin (IL)-6 levels and white blood cell (WBC) counts were measured at the first suspicion of LOS and after 8, 24 and 48 h. RESULTS: Small for gestational age (SGA) infants who were treated with fewer days of antibiotics characterized the fulminant sepsis group. The initial high levels of inflammatory markers were similar in both groups, but as early as 8 h after onset significantly lower levels of SAA, CRP and WBC counts were documented in the fulminant sepsis group. The inflammatory response remained low at 24 and 48 h in the fulminant sepsis group, while in the survivors, significantly increased inflammatory markers were measured. Decreases in the levels of the inflammatory markers preceded episodes of metabolic acidosis and arterial hypotension that were more common in the fulminant sepsis group. Infant mortality correlated inversely with SAA levels at 8 h and with CRP and WBC counts at 24 h after onset. CONCLUSION: SAA, CRP and WBC counts can be used as prognostic markers in LOS in preterm infants, with SAA being the earliest prognostic marker.     

Urinary tract infection in very low birth weight preterm infants

BACKGROUND: The prevalence of urinary tract infection (UTI) in preterm neonates ranges between 4 and 25%. The need for a radiologic investigation has not yet been established in very low birth weight premature newborns (<1500 g birth weight). PATIENTS AND METHODS: For an 11-year period (1990 to 2001), medical records of 62 very low birth weight premature infants admitted to a Level III neonatal intensive care unit and who developed UTI were reviewed retrospectively. Results of renal ultrasound and voiding cystourethrograms were compared between extremely low birth weight infants (birth weight, <1000 g) (Group A, Patient 34) and premature infants with birth weight between 1001 and 1500 g (Group B, Patient 28). RESULTS: UTI was more common in Group A (12.2%) than in Group B (5.7%) infants. Renal ultrasound detected mild renal pelvic dilatation (unilateral or bilateral) in 9 infants in Group A (26%) and in 1 infant in Group B (3.5%). Voiding cystourethrograms were performed in 26 of 34 (76%) infants in Group A and in 17 of the 28 (61%) premature infants in Group B. Vesicourethral reflux (VUR) was observed in 6 infants, 2 in group A (7.7%) and 4 in Group B (23%). CONCLUSIONS: We found that the rate of VUR was lower in very low birth weight premature newborns than that reported in the medical literature among term newborns who developed UTI. VUR was less frequent in extremely low birth weight infants who developed UTI than in infants weighing 1001 to 1500 g.     

Mucolipidosis III type C: first-trimester biochemical and molecular prenatal diagnosis

OBJECTIVES: Mucolipidosis IIIC (MLIIIC) is a rare autosomal recessive lysosomal storage disease resulting from defective mannose 6-phosphate-dependent lysosomal enzyme trafficking; mutations of the gamma subunit of N-acetylglucosamine-1 phosphotransferase (GINAcPT) were recently found to cause its pathogenesis. We report here for the first time prenatal diagnosis (PND) for MLIIIC by means of chorionic villous sampling (CVS). METHODS AND RESULTS: A fetus in a large Bedouin-Moslem family was found to be homozygous for the founder haplotype and the mutational SSCP pattern of MLIIIC. The diagnosis was confirmed by markedly reduced lysosomal enzyme activities in cultured chorionic villi. The molecular identification of the disease-causing mutation in this large Bedouin-Moslem kindred permitted, for the first time, identification of carriers and couples at risk. CONCLUSIONS: The feasibility of early PND for a progressive disabling disease is important for its prevention. Nevertheless, the feasibility of PND raises a serious dilemma since affected individuals might have a variable phenotype and the disease is progressive and non-lethal. In addition, religious and social constraints are important factors to be taken into consideration in the genetic counseling of couples at risk.