Phenotypic variation in CHARGE syndrome remains unexplained. A subcategory of CHARGE patients show overlapping phenotypic characteristics with DiGeorge syndrome (thymic hypo/aplasia, hypocalcemia, T-cell immunodeficiency). Very few have been tested or reported to carry a mutation of the CHD7 (chromodomain helicase DNA-binding domain) gene detected in two-thirds of CHARGE patients. In an attempt to explore the genetic background of a severe CHARGE/DiGeorge phenotype, we performed comparative genomic array hybridization in an infant carrier of a CHD7 mutation. The high-resolution comparative genomic array hybridization revealed interesting findings, including a deletion distal to the DiGeorge region and disruptions in other chromosomal regions of genes implicated in immunological and other functions possibly contributing to the patient’s severe phenotype and early death.

OBJECTIVE: The phenotype associated with heterozygous HNF4A gene mutations has recently been extended to include diazoxide responsive neonatal hypoglycemia in addition to maturity-onset diabetes of the young (MODY). To date, mutation screening has been limited to patients with a family history consistent with MODY. In this study, we investigated the prevalence of HNF4A mutations in a large cohort of patients with diazoxide responsive hyperinsulinemic hypoglycemia (HH). SUBJECTS AND METHODS: We sequenced the ABCC8, KCNJ11, GCK, GLUD1, and/or HNF4A genes in 220 patients with HH responsive to diazoxide. The order of genetic testing was dependent upon the clinical phenotype. RESULTS: A genetic diagnosis was possible for 59/220 (27%) patients. K(ATP) channel mutations were most common (15%) followed by GLUD1 mutations causing hyperinsulinism with hyperammonemia (5.9%), and HNF4A mutations (5%). Seven of the 11 probands with a heterozygous HNF4A mutation did not have a parent affected with diabetes, and four de novo mutations were confirmed. These patients were diagnosed with HI within the first week of life (median age 1 day), and they had increased birth weight (median +2.4 SDS). The duration of diazoxide treatment ranged from 3 months to ongoing at 8 years. CONCLUSIONS: In this large series, HNF4A mutations are the third most common cause of diazoxide responsive HH. We recommend that HNF4A sequencing is considered in all patients with diazoxide responsive HH diagnosed in the first week of life irrespective of a family history of diabetes, once K(ATP) channel mutations have been excluded.

A case of a neonate with congenital chylous ascites resulting from primary lymphatic dysplasia is described. The baby also presented with a sludge ball in the gallbladder that eventually progressed to gallstones. The association of chylous ascites with cholelithiasis in this neonate is discussed.

{BACKGROUND: Adipocyte fatty acid binding protein (a-FABP) has been suggested to play an important role in the pathogenesis of metabolic syndrome. Preterm infants are at risk for the later development of insulin resistance, and, possibly, other components of metabolic syndrome. AIM: To determine circulating levels of a-FABP in preterm infants and examine possible associations of a-FABP with metabolic indices (serum lipids, glucose, and insulin levels, and homeostasis model assessment index of insulin resistance [HOMA-IR]), levels of leptin and adiponectin, anthropometric parameters and weight gain. STUDY DESIGN: Prospective cohort study. SUBJECTS: 55 healthy preterm (mean [SD] gestational age 32.8 [1.8] weeks) and 23 fullterm infants (reference group). OUTCOME MEASURES: Serum a-FABP, lipids, glucose, insulin, leptin and adiponectin levels at 31.9 [10.4] days of life. RESULTS: Serum a-FABP levels did not differ significantly between preterm and fullterm infants. A-FABP levels correlated positively with total-cholesterol [total-C] in both preterm and fullterm infants (beta=0.33; p=0.01 and beta=0.33; p=0.04, respectively). In addition to total-C, weight gain correlated independently with a-FABP levels in preterm infants (beta=0.36

BACKGROUND: The Alberta Infant Motor Scale (AIMS) is a norm-referenced test that assesses the spontaneous motor performance of infants from birth through independent walking (0-18 months). This scale has been utilized for clinical and research purposes in various countries, however, whether the initial standardization in Canadian infants is also representative of other countries’ populations has been questioned. AIM: To assess whether the AIMS needs new reference values for Greek infants. METHODS: A cohort of 424 healthy full-term infants (250 boys and 174 girls), aged between 7 days and 18 months, derived from various areas of the Prefecture of Attica and from all socio-economic classes to ensure a true representation, was studied. The AIMS-scores of Greek infants were compared with the norm-referenced values of the original Canadian population reported by Piper and Darrah. RESULTS: The mean AIMS-scores did not differ significantly between Greek and Canadian infants at any age level from birth to 18 months, except for the 2-<3 month of age when higher scores were observed in Greek infants (p=0.02). There was no significant difference in AIMS-values corresponding to the 5th and 90th percentile between Greek and Canadian infants. Inter-rater reliability was excellent in our study population [ICC: 0.99 (95% CI: 0.99-0.99)]. CONCLUSION: In healthy full-term Greek infants, gross motor maturity assessed by the AIMS during the first 18 months of age, seems to follow a similar course to that of Canadian infants.

Hb Agrinio [α29(B10)Leu→Pro] is a highly unstable variant, classified as a nondeletional α-thalassemia (α-thal) mutation. To date it has only been described in individuals of Greek and Cypriot origin. Evaluation of the phenotypic presentation of 12 Hb Agrinio homozygotes or compound heterozygotes, diagnosed in a single center in Greece during a 15-year period, found a wide clinical expression, ranging from thalassemia intermedia (with or without transfusion requirement) to Hb H hydrops fetalis, with some phenotype-to-genotype correlation. The often severe clinical presentation of Hb Agrinio homozygotes or Hb Agrinio compound heterozygotes, coinheriting severe α-thal determinants, indicates that molecular identification of carriers of the Hb Agrinio mutation should be considered within the context of screening programs involving individuals of Greek and Cypriot origin. Selective molecular investigation of candidate carriers is facilitated by the observation that all heterozygotes for the Hb Agrinio mutation present with at least one hematological parameter implicating an α-thal carrier state.