Practical Recommendations for the Diagnosis and Management of Lysosomal Acid Lipase Deficiency with a Focus on Wolman Disease.

Lysosomal acid lipase deficiency (LAL-D) is an ultra-rare lysosomal storage disease with two distinct phenotypes, an infantile-onset form (formerly Wolman disease) and a later-onset form (formerly cholesteryl ester storage disease). The objective of this narrative review is to examine the most important aspects of the diagnosis and treatment of LAL-D and to provide practical expert recommendations. The infantile-onset form occurs in the first weeks of life and is characterized by malnourishment and failure to thrive due to gastrointestinal impairment (vomiting, diarrhea, malabsorption), as well as systemic inflammation, hepatosplenomegaly, and adrenal calcifications.

Exploring Plasma Coenzyme Q Status in Paediatric Dyslipidaemia.

Coenzyme Q10 (CoQ) is a ubiquitous lipid with different biological functions. In blood, there is a close relationship between CoQ status and cholesterol, which strongly supports the study of both molecules simultaneously. The objective of this study was to evaluate plasma CoQ, lipoprotein concentrations and CoQ/Chol ratio in a cohort of paediatric patients with different types of dyslipidaemias.

Switching to Glycerol Phenylbutyrate in 48 Patients with Urea Cycle Disorders: Clinical Experience in Spain.

Background and objectives: Glycerol phenylbutyrate (GPB) has demonstrated safety and efficacy in patients with urea cycle disorders (UCDs) by means of its clinical trial program, but there are limited data in clinical practice. In order to analyze the efficacy and safety of GPB in clinical practice, here we present a national Spanish experience after direct switching from another nitrogen scavenger to GPB. Methods: This observational, retrospective, multicenter study was performed in 48 UCD patients (age 11.

Intravenous branched-chain amino-acid-free solution for the treatment of metabolic decompensation episodes in Spanish pediatric patients with maple syrup urine disease.

Background: Metabolic decompensation episodes (DEs) in Maple Syrup urine disease (MSUD) result in brain accumulation of toxic branched-chain amino acids (BCAAs) and their respective branched-chain α-keto acids that could induce neuroinflammation, disturb brain bioenergetics, and alter glutamate and glutamine synthesis. These episodes require immediate intervention to prevent irreversible neurological damage. Intravenous (IV) administration of BCAA-free solution could represent a powerful alternative for emergency treatment of decompensations.

Implementation of second-tier tests in newborn screening for the detection of vitamin B related acquired and genetic disorders: results on 258,637 newborns.

Background: Alteration of vitamin B metabolism can be genetic or acquired, and can result in anemia, failure to thrive, developmental regression and even irreversible neurologic damage. Therefore, early diagnosis and intervention is critical. Most of the neonatal cases with acquired vitamin B deficiency have been detected by clinical symptoms and only few of them trough NBS programs.

Discovery of Biomarker Panels for Neural Dysfunction in Inborn Errors of Amino Acid Metabolism.

Patients with inborn errors of amino acid metabolism frequently show neuropsychiatric symptoms despite accurate metabolic control. This study aimed to gain insight into the underlying mechanisms of neural dysfunction. Here we analyzed the expression of brain-derived neurotrophic factor (BDNF) and 10 genes required for correct brain functioning in plasma and blood of patients with Urea Cycle Disorders (UCD), Maple Syrup Urine Disease (MSUD) and controls.

Newborn screening for homocystinurias: Recent recommendations versus current practice.

Purpose: To assess how the current practice of newborn screening (NBS) for homocystinurias compares with published recommendations.

Methods: Twenty-two of 32 NBS programmes from 18 countries screened for at least one form of homocystinuria. Centres provided pseudonymised NBS data from patients with cystathionine beta-synthase deficiency (CBSD, n = 19), methionine adenosyltransferase I/III deficiency (MATI/IIID, n = 28), combined remethylation disorder (cRMD, n = 56) and isolated remethylation disorder (iRMD), including methylenetetrahydrofolate reductase deficiency (MTHFRD) (n = 8).

Plasma coenzyme Q status is impaired in selected genetic conditions.

Identifying diseases displaying chronic low plasma Coenzyme Q (CoQ) values may be important to prevent possible cardiovascular dysfunction. The aim of this study was to retrospectively evaluate plasma CoQ concentrations in a large cohort of pediatric and young adult patients. We evaluated plasma CoQ values in 597 individuals (age range 1 month to 43 years, average 11 years), studied during the period 2005-2016.

The Role of Liver Transplantation in Propionic Acidemia.

Despite optimal medical treatment and strict low-protein diet, the prognosis of propionic acidemia (PA) patients is generally poor. We aim to report our experience with liver transplantation (LT) in the management of PA patients. Six patients with PA received a LT at a mean age of 5.

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: A case report.

Clinical Case: A five-year-old patient, with a diagnosis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, was referred for an ophthalmological examination. He had a history of acute metabolic crises precipitated by intercurrent infections,as well as rhabdomyolysis. The fundoscopic examination revealed a peripapillary chorioretinal atrophy and a diffuse granular appearance of the macular retinal pigment epithelium.

Evolution of maple syrup urine disease in patients diagnosed by newborn screening versus late diagnosis.

Maple syrup urine disease (MSUD) is a rare metabolic disorder for which the newborn screening (NBS) is possible but it has not been yet implemented for most Spanish regions. In the present study, we assess the clinical features and outcome of 14 MSUD Spanish patients with similar treatment protocol diagnosed either by NBS or by clinical symptoms. Eight patients were detected by NBS, four classic and four moderate MSUD.

Coenzyme Q and Pyridoxal Phosphate Deficiency Is a Common Feature in Mucopolysaccharidosis Type III.

Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by deficiencies of lysosomal enzymes catalyzing degradation of glycosaminoglycans (GAGs). Previously, we reported a secondary plasma coenzyme Q (CoQ) deficiency in MPS patients. For this study, nine MPS patients were recruited in the Hospital Sant Joan de Déu (HSJD, Barcelona) and two patients in the Neurometabolic Unit, National Hospital (NMU, London), to explore the nutritional status of MPS type III patients by analyzing several vitamins and micronutrients in blood and in cerebrospinal fluid.

Urea cycle disorders in Spain: an observational, cross-sectional and multicentric study of 104 cases.

Background: Advances in the diagnosis and treatment of urea cycle disorders (UCDs) have led to a higher survival rate. The purpose of this study is to describe the characteristics of patients with urea cycle disorders in Spain.

Methods: Observational, cross-sectional and multicenter study.

Clinical and biochemical outcome after hydroxocobalamin dose escalation in a series of patients with cobalamin C deficiency.

Background: CblC deficiency produces a combination of methylmalonic aciduria (MMA) and homocystinuria (HCU), and is the most common error of cobalamin metabolism. Patients present a wide spectrum of symptoms, ranging from early severe multisystemic forms, to milder late-onset phenotypes. Cognitive and visual impairment are nearly constant.

[Experience with ketogenic diet as treatment for refractory epilepsy].

Introduction: Epilepsy is a disease where most patients have a good control with pharmacological antiepileptic treatment. Nevertheless, 25% of the patients have a refractory epilepsy to usual antiepileptic drugs. Ketogenic diet is one of the treatment options for this type of epilepsy.

Long-chain polyunsaturated fatty acid concentration in patients with inborn errors of metabolism.

Introduction: Long-chain polyunsaturated fatty acid (LCPUFA) can be provided by diet (fatty fish, eggs, viscera and human milk) or synthetised from essential fatty acids linoleic and α-linolenic acids through the microsomal pathway. However, endogenous LCPUFA synthesis is rather low, especially for docosahexaenoic (DHA), and seems insufficient to achieve normal DHA values in individuals devoid of preformed dietary supply. Inborn errors of metabolism (IEMs) are therefore diseases with a special risk for LCPUFA deficient status.

Assessment of plasma ammonia and glutamine concentrations in urea cycle disorders.

Objectives: To analyze the association between ammonia and glutamine used for metabolic control in inherited urea cycle disorders (UCD) in a large series of patients.

Design And Methods: Paired plasma amino acid-ammonia data from 26 UCD patients were analyzed (n=921).

Results: Increased plasma glutamine values were consistently observed in UCD patients, despite normal plasma ammonia concentrations, especially for mitochondrial UCD.