Two novel mutations in TCIRG1 induced infantile malignant osteopetrosis: a case report.

BACKGROUND: Infantile malignant osteopetrosis (IMO) is a rare autosomal recessive disease characterized by a higher bone density in bone marrow caused by the dysfunction of bone resorption. Clinically, IMO can be diagnosed with medical examination, bone mineral density test and whole genome sequencing. CASE PRESENTATION: We present the case of a 4-month-old male infant with abnormal skull development, hypocalcemia and premature closure of the cranial sutures. Due to the hyper bone density showed by his radiographic examination, which are characteristic patterns of IMO, we speculated that he might be an IMO patient. In order to confirm this diagnosis, a high-precision whole exome sequencing of the infant and his parents was performed. The analysis of high-precision whole exome sequencing results lead to the identification of two novel heterozygous mutations c.504-1G > C (a splicing site mutation) and c.1371delC (p.G458Afs*70, a frameshift mutation) in gene TCIRG1 derived from his parents. Therefore, we propose that there is a close association between these two mutations and the onset of IMO. CONCLUSIONS: To date, these two novel mutations in gene TCIRG1 have not been reported in the reference gene database of Chinese population. These variants have likewise not been reported outside of China in the Genome Aggregation Database (gnomAD). Our case suggests that the use of whole exome sequencing to detect these two mutations will improve the identification and early diagnosis of IMO, and more specifically, the identification of homozygous individuals with TCIRG1 gene mutation. We propose that these mutations in gene TCIRG1 could be a novel therapeutic target for the IMO in the future.

[Effects of postnatal growth retardation on early neurodevelopment in premature infants with intrauterine growth retardation].

OBJECTIVE: To study the effects of postnatal growth retardation on early neurodevelopment in premature infants with intrauterine growth retardation (IUGR). METHODS: A retrospective analysis was performed on the clinical data of 171 premature infants who were born between May 2008 and May 2012 and were followed up until a corrected gestational age of 6 months. These infants were classified into two groups: IUGR group (n=40) and appropriate for gestational age (AGA) group (n=131). The growth retardation rates at the corrected gestational ages of 40 weeks, 3 months, and 6 months, as well as the neurodevelopmental outcome (evaluated by Gesell Developmental Scale) at corrected gestational ages of 3 and 6 months, were compared between the two groups. RESULTS: The growth retardation rate in the IUGR group was significantly higher than in the AGA group at the corrected gestational ages of 40 weeks, 3 months, and 6 months. All five developmental quotients evaluated by Gesell Developmental Scale (gross motor, fine motor, language, adaptability and individuality) in the IUGR group were significantly lower than in the AGA group at the corrected gestational ages of 3 months. At the corrected gestational age of 6 months, the developmental quotients of fine motor and language in the IUGR group were significantly lower than in the AGA group, however, there were no significant differences in the developmental quotients of gross motor, adaptability and individuality between the two groups. All five developmental quotients in IUGR infants with catch-up lag in weight were significantly lower than in IUGR and AGA infants who had caught up well. CONCLUSIONS: Growth retardation at early postnatal stages may adversely affect the early neurodevelopment in infants with IUGR.

[Risk factors for extrauterine growth retardation at discharge in premature infants].

OBJECTIVE: To study the incidence and risk factors for extrauterine growth retardation (EUGR) at discharge in premature infants. METHODS: A retrospective analysis was performed on 596 premature infants who were admitted to the neonatal intensive care unit between 2006 and 2010. These subjects were classified into EUGR (n=217) and non-EUGR groups (n=379) based on the body weight at discharge. The risk factors for the occurrence of EUGR were studied by multivariate logistic regression analysis. RESULTS: Based on the body weight, length, and head circumference, the incidence of EUGR at discharge was 36.4% (217 cases), 42.0% (250 cases), and 22.8% (136 cases), respectively. Low gestational age, low birth weight, intrauterine growth retardation (IUGR), delayed enteral feeding and complications of the respiratory system were identified as risk factors for EUGR (OR=6.508, 14.522, 5.101, 1.366, and 1.501, respectively). CONCLUSIONS: The incidence of EUGR might be greatly decreased by strengthening the perinatal care, reducing the incidence of premature delivery and IUGR, undertaking early enteral feeding, and actively preventing postnatal complications.

[Effects of recombinant human erythropoietin on neurointelligence development in very low birth weight infants].

OBJECTIVE: To evaluate the clinical effects of the early use of recombinant human erythropoietin (rhEPO) on the neurointelligence development in very low birth weight infants (VLBWI). METHODS: Seventy-eight VLBWI were divided into rhEPO treatment group (n=35) and control group (n=43) according to the choice of their parents. Neonatal behavioral neurological assessment (NBNA) was performed at 40 weeks of corrected gestational age. The Gesell Developmental Schedules were used for neurodevelopmental evaluation at 3, 6, and 12 months of corrected age. The abnormal rates of auditory brainstem response (ABR) and cranial ultrasound were evaluated at 6 months of corrected age. RESULTS: The rhEPO treatment group had significantly higher NBNA scores at 40 weeks of corrected gestational age than the control group (P<0.05). The adaptability at 3 months of corrected age, the gross motor, adaptability, and sociability at 6 months, and the gross motor, adaptability, fine motor, sociability, and language at 12 months were significantly better in the rhEPO treatment group than in the control group (P<0.05). The abnormal rates of ABR and cranial ultrasound in the rhEPO treatment group were significantly lower than in the control group at 6 months of corrected age (P<0.05). CONCLUSIONS: Early use of rhEPO can promote the early recovery of neurological symptoms and improve the cognitive, motor, and language abilities in VLBWI due to its protective effects on the nervous system.