Diagnosis, treatment, and follow-up of patients with hypophosphatasia.

Introduction: Hypophosphatasia is a rare inherited systemic metabolic disorder, with an estimated prevalence in the severe forms of the disease of 1/100.000-1/300.000, that affects the typical architecture of bone, leading to defective mineralization during growth and remodeling.

Concordance Between Biochemical and Molecular Diagnosis Obtained by WES in Mexican Patients with Inborn Errors of Intermediary Metabolism: Utility for Therapeutic Management.

Biochemical phenotyping has been the milestone for diagnosing and managing patients affected by inborn errors of intermediary metabolism (IEiM); however, identifying the genotype responsible for these monogenic disorders greatly contributes to achieving these goals. Herein, whole-exome sequencing (WES) was used to determine the genotypes of 95 unrelated Mexican pediatric patients suspected of having IEiM. They were classified into those bearing specific biochemical abnormalities (Group 1), and those presenting unspecific biochemical profiles (Group 2).

Consenso mexicano de tirosinemia tipo 1.

Introduction: Tyrosinemia type 1 is a rare disease with autosomal recessive inheritance, featuring various clinical manifestations. These may encompass acute neonatal liver failure, neonatal cholestatic syndrome, chronic hepatitis, cirrhosis, hepatocellular carcinoma, and, alternatively, kidney disorders like renal tubular acidosis, Fanconi syndrome, hypophosphatemic rickets, among other alterations. Diagnosis relies on detecting toxic metabolites in the blood and urine, ideally confirmed through molecular testing.

A Review of Disparities and Unmet Newborn Screening Needs over 33 Years in a Cohort of Mexican Patients with Inborn Errors of Intermediary Metabolism.

Advances in an early diagnosis by expanded newborn screening (NBS) have been achieved mainly in developed countries, while populations of middle- and low-income countries have poor access, leading to disparities. Expanded NBS in Mexico is not mandatory. Herein, we present an overview of the differences and unmet NBS needs of a group of Mexican patients with inborn errors of intermediary metabolism (IEiM), emphasizing the odyssey experienced to reach a diagnosis.

Functional characterization of the p.(Gln195His) or Tainan and novel p.(Ser184Cys) or Toluca glucose-6-phosphate dehydrogenase (G6PD) gene natural variants identified through Mexican newborn screening for glucose-6-phosphate dehydrogenase deficiency.

Background: Newborn screening for glucose-6-phosphate dehydrogenase deficiency (G6PDd) was implemented in Mexico beginning in 2017. In a Mexican population, genotyping analysis of G6PD as a second-tier method identified a previously unreported missense variant, p.(Ser184Cys), which we propose to call "Toluca", and the extremely rare p.

An Updated Mutational Spectrum of Phenylketonuria in Mexican Patients Attending a Single Center: Biochemical, Clinical-Genotyping Correlations.

Establishing the genotypes of patients with hyperphenylalaninemia (HPA)/phenylketonuria (PKU, MIM#261600) has been considered a cornerstone for rational medical management. However, knowledge of the phenylalanine hydroxylase gene ( mutational spectrum in Latin American populations is still limited. Herein, we aim to update the mutational spectrum in the largest cohort of HPA/PKU Mexican patients ( = 124) reported to date.

Mutational spectrum of Mexican patients with tyrosinemia type 1: In silico modeling and predicted pathogenic effect of a novel missense FAH variant.

Background: Tyrosinemia type 1 (HT1, MIM#276700) is caused by a deficiency in fumarylacetoacetate hydrolase (FAH) and it is associated with severe liver and renal disfunction. At present, the mutational FAH (15q25.1, MIM*613871) spectrum underlying HT1 in the Mexican population is unknown.

Mutational spectrum of PTS gene and in silico pathological assessment of a novel variant in Mexico.

Background: Tetrahydrobiopterin (BH4) is the cofactor for 6-pyruvoyl-tetrahydropterin synthase (PTPS); it is involved in BH4 biosynthesis and is encoded by PTS gene. Its deficiency (PTPSD) is characterized by hyperphenylalaninemia (HPA) and deficit in central monoamine neurotransmitters. We describe the clinical and mutational spectrum of five patients with PTPSD, from four unrelated Mexican families.

In silico prediction of the pathogenic effect of a novel variant of BCKDHA leading to classical maple syrup urine disease identified using clinical exome sequencing.

Maple syrup urine disease (MSUD) is a metabolic disorder caused by mutations in three of the branched-chain α-keto acid dehydrogenase complex (BCKDC) genes. Classical MSUD symptom can be observed immediately after birth and include ketoacidosis, irritability, lethargy, and coma, which can lead to death or irreversible neurodevelopmental delay in survivors. The molecular diagnosis of MSUD can be time-consuming and difficult to establish using conventional Sanger sequencing because it could be due to pathogenic variants of any of the BCKDC genes.

Kernicterus in a boy with ornithine transcarbamylase deficiency: A case report.

Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle defect associated with severe and usually fatal hyperammonemia. This study describes a patient with early onset lethal OTCD due to a known pathogenic variant (c.298+1G>A), as well as the novel autopsy finding of kernicterus with relatively low blood concentration of unconjugated bilirubin (UCB) (11.

Hepatorenal Tyrosinemia in Mexico: A Call to Action.

Hepatorenal tyrosinemia is a treatable metabolic disease characterized by progressive liver failure, renal damage and pronounced coagulopathy. Its clinical diagnosis is difficult because of its low prevalence and heterogeneous symptoms. In developed countries, expanded newborn screening, based on succinylacetone quantification by tandem mass spectrometry, has been very valuable in the early detection of hepatorenal tyrosinemia, providing the opportunity for rapid treatment of affected patients.

[COMPARISON OF FREE CARNITINE LEVELS WITH NUTRITIONAL STATUS IN INFANTILE NEPHROPATHYC CISTINOSIS PATIENTS].

Introduction: infantile nephropathic cystinosis (INC) is an autosomal recessive disorder that causes defects in cystine transport with subsequent accumulation in almost all body tissues, especially kidneys. There are few studies regarding the nutritional status assessment of patients with INC. It has been reported that patients with INC showed increased urinary losses of carnitine, resulting in plasma and muscle carnitine deficiency also increased metabolic requirements of carnitine in this patients have also been proposed, but to date carnitine supplementation is controversial.

[GASTROSTOMY POSITIVELY AFFECTS NUTRITIONAL STATUS AND DIMINISHES HOSPITAL DAYS IN PATIENTS WITH INBORN ERRORS OF METABOLISM].

Introduction: the nutrition management of patients with inborn errors of metabolism (IEM) requires the permanent use of elemental medical formulas whose organoleptic characteristics sometimes impede oral acceptance. In addition, these patients may have gastrointestinal disorders and require constant use of drugs, that often complicate treatment adherence, thereby committing their nutritional status and disease control. Gastrostomy is an alternative to facilitate feeding and treatment, but its use is controversial.

Tyrosinemia type I: clinical and biochemical analysis of patients in Mexico.

Introduction: Hepatorenal tyrosinemia (HT1) is a treatable, inherited, metabolic disease characterized by progressive liver failure with pronounced coagulopathy. The aim of this study is to describe the clinical, biochemical, and histopathological findings in a group of Mexican HT1 patients and their outcome.

Material And Methods: Medical records of HT1 patients diagnosed between 1995 and 2011 were analyzed.

CTNS gene analysis emphasizes diagnostic value of eye examination in patients with cystinosis.

Classic nephropathic cystinosis (CNC) is an autosomal recessive and infrequent inborn metabolic disease that should be suspected in all children who show failure to thrive and renal Fanconi syndrome (RFS). Slit-lamp examination reveals pathognomonic corneal deposits of cystine crystals in virtually all affected individuals after 12-16 mo of age. A diagnosis of CNC is difficult to confirm in children living in Mexico and most Latin American countries, because cystine levels can be measured only at a few locations.

Analysis of the CTNS gene in nephropathic cystinosis Mexican patients: report of four novel mutations and identification of a false positive 57-kb deletion genotype with LDM-2/exon 4 multiplex PCR assay.

Objective: Identify CTNS gene mutations in nephropathic cystinosis Mexican patients.

Subjects And Methods: Eleven patients were included, nine presenting infantile nephropathic cystinosis and two siblings with the juvenile phenotype. The common 57-kb deletion was detected by multiplex PCR using large deletion marker-2 (LDM-2)/exon 4 set primers.

[Increased mortality and disability in a cohort of Mexican children with maple syrup urine disease].

Introduction: Maple syrup urine disease (MSUD) is a genetic disorder that produces ketoacidosis crises and neurological complications often leading to death. The age of diagnosis and treatment determine a child's adequate and healthy outcome.

Objective: Describe the characteristics of a pediatric Mexican cohort with MSUD.