[Acute liver failure related to inherited metabolic diseases in young children]. / Fallo hepático aguda asociado a enfermedades metabólicas hereditarias en niños pequeños.

INTRODUCTION: Pediatric acute liver failure (ALF) due to inherited metabolic diseases (IMD) is a rare life-threatening condition with a poor prognosis. Early intervention may be lifesaving. OBJECTIVE: To describe clinical presentation, investigation and outcomes of ALF related to IMD in young children. MATERIAL AND METHODS: Retrospective review of the medical records of children aged up to 24 months, admitted to a tertiary pediatric and neonatal Intensive Care Unit during a 27-year period, fulfilling the ALF criteria, with documented metabolic etiology. RESULTS: From 34 ALF cases, 18 were related to IMD: galactosemia (4), mitochondrial DNA depletion syndrome (MDS) (3), ornithine transcarbamilase deficiency (3), congenital defects of glycosylation (2), tyrosinemia type 1 (2), long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (1), hereditary fructose intolerance (1), classic methylmalonic aciduria (1) and citrulinemia type 1 (1). The median age was 1.3 months. At least one previous suggestive sign/symptom of IMD (vomiting, failure to thrive, hypotonia or developmental delay) was observed in 67% of the cases. The most common physical signs at admission included: hepatomegaly (72%), jaundice (67%) and encephalopathy (44%). The peak laboratorial findings were: mean international normalizad ratio 4.5, median lactate 5mmol/L, mean bilirubin 201µmol/L, median alanine aminotransferase (ALT) 137 UI/L and median ammonia 177µmol/L. One patient was submitted to liver transplant in ALF context (MSD). The mortality rate was 44%. DISCUSSION: The identification of IMD as a frequent cause of ALF allowed specific therapeutic measures and adequate family counselling. Particular clinical features and moderated ALT and bilirubin levels can lead to its suspicion.

Galactose Epimerase Deficiency: Expanding the Phenotype.

Galactose epimerase deficiency is an inborn error of metabolism due to uridine diphosphate-galactose-4'-epimerase (GALE) deficiency. We report the clinical presentation, genetic and biochemical studies in two siblings with generalized GALE deficiency.Patient 1: The first child was born with a dysmorphic syndrome. Failure to thrive was noticed during the first year. Episodes of heart failure due to dilated cardiomyopathy, followed by liver failure, occurred between 12 and 42 months. The finding of a serum transferrin isoelectrofocusing (IEF) type 1 pattern led to the suspicion of a congenital disorder of glycosylation (CDG). Follow-up disclosed psychomotor disability, deafness, and nuclear cataracts.Patient 2: The sibling of patient 1 was born with short limbs and hip dysplasia. She is deceased in the neonatal period due to intraventricular hemorrhage in the context of liver failure. Investigation disclosed galactosuria and normal transferrin glycosylation.Next-generation sequence panel analysis for CDG syndrome revealed the previously reported c.280G>A (p.[V94M]) homozygous mutation in the GALE gene. Enzymatic studies in erythrocytes (patient 1) and fibroblasts (patients 1 and 2) revealed markedly reduced GALE activity confirming generalized GALE deficiency. This report describes the fourth family with generalized GALE deficiency, expanding the clinical spectrum of this disorder, since major cardiac involvement has not been reported before.

Child with multiple fractures: a rare presentation of a common disease.

Bone fractures are not uncommon in paediatric age. However, when recurrent, an underlying clinical condition must not be excluded. We describe the case of a boy aged 7 years, referred for investigation of recurrent bone fractures. Personal and family histories were unremarkable. Physical examination was normal. Almost all primary bone disorders were excluded. Additional laboratory investigations ruled out the majority of secondary causes of bone fragility. Coeliac disease (CD) serologies, however, were positive, and duodenal biopsies confirmed this diagnosis (Marsh III B). On a gluten-free diet, he suffered no more fractures and the bone mineral density improved. CD was also confirmed in his asymptomatic older brother. It is essential to diagnose CD as early as possible in order to minimise the compromise in bone health and prevent other complications of the disease. First-degree relatives should always be screened for the disease, even asymptomatic ones.

Group B streptococcal neonatal parotitis.

Acute neonatal parotitis (ANP) is a rare condition, characterised by parotid swelling and other local inflammatory signs. The most common pathogen is Staphylococcus aureus, but other organisms can be implicated. We describe the case of a 13-day-old term newborn, previously healthy, with late-onset group B Streptococcus (GBS) bacteraemia with ANP, who presented with irritability, reduced feeding and tender swelling of the right parotid. Laboratory evaluation showed neutrophilia, elevated C reactive protein and procalcitonin, with normal serum amylase concentration. Ultrasound findings were suggestive of acute parotitis. Empiric antibiotic therapy was immediately started and adjusted when culture results became available. The newborn was discharged after 10 days, with clinical improvement within the first 72 h. Although S. aureus is the most common pathogen implicated in ANP, GBS should be included in the differential diagnosis.

Narcolepsy in pediatric age - Experience of a tertiary pediatric hospital.

Narcolepsy, a chronic disorder of the sleep-wake cycle of multifactorial etiology, is characterized by excessive daytime sleepiness, often associated with cataplexy, hypnagogic/hypnopompic hallucinations and sleep paralysis. Both early clinical suspicion and therapeutic approach are essential for promotion of cognitive development and social integration of these children. The authors present a descriptive retrospective study of a series of eight children in whom symptoms first started between 6.8 and 10.5 years of age. Diagnostic delay ranged from 4 months to 2 years. One child had H1N1 flu vaccination eight months before the clinical onset. The first multiple sleep latency test was positive in 6 of 8 cases. All cases were treated with methylphenidate, and venlafaxine was associated in 4 of them. In one case the initial therapy was exclusively behavioral. In all cases, symptomatic improvement, better school performance and social integration were achieved after therapeutic adjustment.