Background Persistent neonatal hypoglycemia, owing to the possibility of severe neurodevelopmental consequences, is a leading cause of neonatal care admission. Hyperinsulinemic hypoglycemia is often resistant to dextrose infusion and needs rapid diagnosis and treatment. Several congenital conditions, from single gene defects to genetic syndromes should be considered in the diagnostic approach. Kabuki syndrome type 1 (MIM# 147920) and Kabuki syndrome type 2 (MIM# 300867), can be associated with neonatal hyperinsulinemic hypoglycemia. Patient presentation We report a female Italian (Sicilian) child, born preterm at 35 weeks gestation, with persistent hypoglycemia. Peculiar facial dysmorphisms, neonatal hypotonia, and cerebellar vermis hypoplasia raised suspicion of Kabuki syndrome. Hyperinsulinemic hypoglycemia was confirmed with glucagon test and whole-exome sequencing (WES) found a novel heterozygous splicing-site mutation (c.674-1G > A) in KMT2D gene. Hyperinsulinemic hypoglycemia was successfully treated with diazoxide. At 3 months corrected age for prematurity, a mild global neurodevelopmental delay, postnatal weight and occipitofrontal circumference growth failure were reported. Conclusions Kabuki syndrome should be considered when facing neonatal persistent hypoglycemia. Diazoxide may help to improve hyperinsulinemic hypoglycemia. A multidisciplinary and individualized follow-up should be carried out for early diagnosis and treatment of severe pathological associated conditions.

Introduction Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, also known as Hay-Wells syndrome, is a rare genetic syndrome with ectodermal dysplasia. About 100 patients have been reported to date. It is associated to a heterozygous mutation of the tumor protein p63 (TP63) gene, located on chromosome 3q28. Typical clinical manifestations include: filiform ankyloblepharon adnatum (congenital adherence of the eyelids), ectodermal abnormalities (sparse and frizzy hair, skin defects, nail alterations, dental changes and hypohidrosis), and cleft lip/palate. Diagnostic suspicion is based on clinical signs and confirmed by genetic testing. Patient’s presentation We hereby report on a female newborn with erythroderma, thin lamellar desquamations, extensive skin erosions, sparse and wiry hair, filiform ankyloblepharon adnatum, agenesis of the lachrymal puncta, cleft palate and nail dysplasia. Her phenotype was compatible with AEC syndrome. Then, based on the clinical suspicion, sequencing analysis of the TP63 gene was performed, and revealed a de novo novel missense mutation. Eyelids adherence and cleft palate underwent surgical correction, while skin erosions were treated with topical antibiotics/antifungals and emollient/re-epithelizing creams. A surgical reconstruction is presently planned for the agenesis of the lachrymal puncta. The infant currently is 17 months of age and is included in a multidisciplinary follow-up. At present shows growth impairment and mild developmental delay, and typical signs of ectodermal dysplasia with small areas of dermatitis lesions on the scalp, without further abnormalities. Conclusions Our report underlines the relevance of an early and careful clinical evaluation in neonates with ankyloblefaron, facial dysmorphism, and signs of ectodermal dysplasia. In these cases, the suspicion of AEC syndrome must be promptly raised, and sequencing analysis of TP63 early performed as well. An individualized, multidisciplinary and long-term follow-up should be guaranteed to affected subjects and their families, also to identify associated morbidities and prevent possible serious complications and adverse outcomes.

Introduction Autosomal recessive polycystic kidney disease (ARPKD; MIM#263200) is one of the most frequent pediatric renal cystic diseases, with an incidence of 1:20,000. It is caused by mutations of the PKHD1 gene, on chromosome 6p12. The clinical spectrum is highly variable, ranging from late-onset milder forms to severe perinatal manifestations. The management of newborns with severe pulmonary insufficiency is challenging, and causes of early death are sepsis or respiratory failure. In cases of massive renal enlargement, early bilateral nephrectomy and peritoneal dialysis may reduce infant mortality. However, there is no conclusive data on the role of surgery, and decision-making is driven by patient’s clinical condition and expertise of the center. Patient presentation We hereby describe a preterm female newborn with perinatal, rapid and bilateral, abnormal growth of both kidneys, respiratory failure and initial signs of liver disease. She was subsequently confirmed to be affected by a rare and severe homozygous mutation of the PKHD1 gene, inherited from both her consanguineous parents. Our patient died 78 days after birth, due to a fungal sepsis which worsened her respiratory insufficiency. Conclusions This patient report shows some of the clinical and ethical issues of neonatal ARPKD, and the need of multidisciplinary approach and good communication with the family. Target next generation sequencing (NGS) techniques may guide and support clinicians, as well as guarantee to these patients the most appropriate clinical management, avoiding unnecessary and/or disproportionate treatments.

Background Mitochondrial diseases, also known as oxidative phosphorylation (OXPHOS) disorders, with a prevalence rate of 1:5000, are the most frequent inherited metabolic diseases. Leigh Syndrome French Canadian type (LSFC), is caused by mutations in the nuclear gene (2p16) leucine-rich pentatricopeptide repeat-containing (LRPPRC). It is an autosomal recessive neurogenetic OXPHOS disorder, phenotypically distinct from other types of Leigh syndrome, with a carrier frequency up to 1:23 and an incidence of 1:2063 in the Saguenay-Lac-St Jean region of Quebec. Recently, LSFC has also been reported outside the French-Canadian population. Patient presentation We report a male Italian (Sicilian) child, born preterm at 28 + 6/7 weeks gestation, carrying a novel LRPPRC compound heterozygous mutation, with facial dysmorphisms, neonatal hypotonia, non-epileptic paroxysmal motor phenomena, and absent sucking-swallowing-breathing coordination requiring, at 4.5 months, a percutaneous endoscopic gastrostomy tube placement. At 5 months brain Magnetic Resonance Imaging showed diffuse cortical atrophy, hypoplasia of corpus callosum, cerebellar vermis hypoplasia, and unfolded hippocampi. Both auditory and visual evoked potentials were pathological. In the following months Video EEG confirmed the persistence of sporadic non epileptic motor phenomena. No episode of metabolic decompensation, acidosis or ketosis, frequently observed in LSFC has been reported. Actually, aged 14 months corrected age for prematurity, the child shows a severe global developmental delay. Metabolic investigations and array Comparative Genomic Hybridization (aCGH) results were normal. Whole-exome sequencing (WES) found a compound heterozygous mutation in the LRPPRC gene, c.1921–7A > G and c.2056A > G (p.Ile686Val), splicing-site and missense variants, inherited from the mother and the father, respectively. Conclusions We first characterized the clinical and molecular features of a novel LRPPRC variant in a male Sicilian child with early onset encephalopathy and psychomotor impairment. Our patient showed a phenotype characterized by a severe neurodevelopmental delay and absence of metabolic decompensation attributable to a probable residual enzymatic activity. LRPPRC is a rare cause of metabolic encephalopathy outside of Québec. Our patient adds to and broaden the spectrum of LSFC phenotypes. WES analysis is a pivotal genetic test and should be performed in infants and children with hypotonia and developmental delay in whom metabolic investigations and aCGH are normal.

Objective Methemoglobinemia (MetHb) is a rare congenital or acquired cause of infantile cyanosis. We examined the role of MetHb in a neonatal intensive care unit (NICU). Study Design A retrospective observational study was conducted reviewing blood gas analyses of hospitalized newborns over a 2-year period. MetHb-positive patients (MetHb >1.8%) were matched with a control group for gestational age, weight, disease, and illness severity at admission. Maternal, neonatal, clinical, and laboratory parameters were collected and analyzed in both groups. Results MetHb incidence was 6%. The mean MetHb in the case group was 7.2%, and the first positive samples were observed at a mean of 22 days of life, 6 days prior to clinical or culture-proven sepsis. We identified low maternal age (31 vs. 34 years; p = 0.038), sepsis (90 vs. 45%; p = 0.022), and protracted parenteral nutrition (46 vs. 23 days; p = 0.013) as risk factors for MetHb, and early minimal enteral feeding as protective factor (12th vs. 9th day; p = 0.038). Conclusion MetHb has a high occurrence in NICU and can be a helpful prognostic indicator of an infectious process. Understanding and prompt identification of MetHb can allow pediatricians to implement a life-saving therapy.