TANGO2-related rhabdomyolysis symptoms are associated with abnormal autophagy functioning.

Patients with pathogenic variants in the gene suffer from severe and recurrent rhabdomyolysis episodes precipitated by fasting. Autophagy functioning was analyzed , in primary skeletal myoblasts from TANGO2 patients, in basal and fasting conditions, and mutations were associated with reduced LC3-II levels upon starvation. In zebrafish larvae, inhibition induced locomotor defects which were exacerbated by exposure to atorvastatin, a compound known to cause rhabdomyolysis.

Circulatory response to exercise relative to oxygen uptake assessed in the follow-up of patients with fatty acid beta-oxidation disorders.

Patients with fatty acid oxidation disorders (FAODs) experience muscle symptoms due to impaired ATP metabolism and the toxicity of accumulated mitochondrial FAO substrates or intermediates, especially during catabolic states. A major issue is the absence of specific and sensible biomarkers to evaluate metabolic equilibrium. The relationship between cardiac output (Q) and oxygen consumption (VO) during incremental exercise (dQ/dVO) provides an indirect surrogate of mitochondrial function.

Consolidating the Role of Mutated ATP2B2 in Neurodevelopmental and Cerebellar Pathologies.

Plasma membrane calcium ATPases (PMCAs) encoded by ATP2B genes have been implicated in Mendelian diseases with ataxia, dystonia, and intellectual disability. Work to date has shown that ATP2B2 (encoding PMCA2) is required for synaptic function and Purkinje-cell integrity in the cerebellum. A recent case series has linked ATP2B2 to a novel entity, characterized by neurodevelopmental and movement phenotypes, in only seven individuals.

Cellular mechanisms of acute rhabdomyolysis in inherited metabolic diseases.

Acute rhabdomyolysis (RM) constitutes a life-threatening emergency resulting from the (acute) breakdown of skeletal myofibers, characterized by a plasma creatine kinase (CK) level exceeding 1000 IU/L in response to a precipitating factor. Genetic predisposition, particularly inherited metabolic diseases, often underlie RM, contributing to recurrent episodes. Both sporadic and congenital forms of RM share common triggers.

Late-onset refractory hemolytic anemia in siblings treated for methionine synthase reductase deficiency: A rare complication possibly prevented by hydroxocobalamin dose escalation?

Methionine synthase reductase deficiency (cblE) is a rare autosomal recessive inborn error of cobalamin metabolism caused by pathogenic variants in the methionine synthase reductase gene (). Patients usually exhibit early-onset bone marrow failure with pancytopenia including megaloblastic anemia. The latter can remain isolated or patients may present developmental delay and rarely macular dysfunction.

Biomarkers for the diagnosis and monitoring of nitrous oxide intoxication: objectives and methodology of the SFBC Working Group.

The recreational use of nitrous oxide (N2O) is an emerging public health issue. Chronic N2O abuse may result in various clinical symptoms, encompassing neurological, psychiatric and cardiovascular outcomes. Despite the difficulties for the laboratory investigation of N2O intoxication, there is currently no guidelines in France to help both clinicians and biologists use appropriate biomarkers for the diagnosis and monitoring of patients with clinical symptoms potentially related to N2O intoxication.

Pubertal origin of growth retardation in inborn errors of protein metabolism: A longitudinal cohort study.

Objectives: Inherited amino-acid metabolism disorders (IAAMDs) require lifelong protein-restricted diet. We aimed to investigate: 1/ whether IAAMDs was associated with growth, pubertal, bone mineral apparent density (BMAD) or body composition impairments; 2/ associations linking height, amino-acid mixture (AAM), plasma amino-acids and IGF1 concentrations.

Design: Retrospective longitudinal study of 213 patients with neonatal-onset urea cycle disorders (UCD,n = 77), organic aciduria (OA,n = 89), maple syrup urine disease (MSUD,n = 34), or tyrosinaemia type 1 (n = 13).

Citrulline in the management of patients with urea cycle disorders.

Background: Treatment recommendations for urea cycle disorders (UCDs) include supplementation with amino acids involved in the urea cycle (arginine and/or citrulline, depending on the enzyme deficiency), to maximize ammonia excretion through the urea cycle, but limited data are available regarding the use of citrulline. This study retrospectively reviewed clinical and biological data from patients with UCDs treated with citrulline and/or arginine at a reference center since 1990. The aim was to describe the prescription, impact, and safety of these therapies.

Initial presentation, management and follow-up data of 33 treated patients with hereditary tyrosinemia type 1 in the absence of newborn screening.

Hereditary tyrosinemia type 1 (HT1) is a rare autosomal recessive disorder of phenylalanine and tyrosine catabolism due to a deficiency of fumarylacetoacetate hydrolase. HT1 has a large clinical spectrum with acute forms presenting before six months of age, subacute forms with initial symptoms occurring between age 6 and 12 months, and chronic forms after 12 months of age. Without treatment, HT1 results in the accumulation of toxic metabolites leading to liver disease, proximal tubular dysfunction, and porphyria-like neurological crises.

Efficacy and pharmacokinetics of betaine in CBS and cblC deficiencies: a cross-over randomized controlled trial.

Background: Betaine is an "alternate" methyl donor for homocysteine remethylation catalyzed by betaine homocysteine methyltransferase (BHMT), an enzyme mainly expressed in the liver and kidney. Betaine has been used for more than 30 years in pyridoxine non-responsive cystathionine beta-synthase (pnrCBS) and cobalamin C (cblC) deficiencies to lower the hyperhomocysteinemia, although little is known about the optimal therapeutic dosage and its pharmacokinetic in these patients.

Aims: We compared 2 betaine doses (100 mg/kg/day vs.

FDX2 and ISCU Gene Variations Lead to Rhabdomyolysis With Distinct Severity and Iron Regulation.

Background And Objectives: To determine common clinical and biological traits in 2 individuals with variants in and , displaying severe and recurrent rhabdomyolyses and lactic acidosis.

Methods: We performed a clinical characterization of 2 distinct individuals with biallelic or variants from 2 separate families and a biological characterization with muscle and cells from those patients.

Results: The individual with variants was clinically more affected than the individual with variants.

Liver and brain differential expression of one-carbon metabolism genes during ontogenesis.

One-carbon metabolism (1C metabolism) is of paramount importance for cell metabolism and mammalian development. It is involved in the synthesis or modification of a wide variety of compounds such as proteins, lipids, purines, nucleic acids and neurotransmitters. We describe here the evolution of expression of genes related to 1C metabolism during liver and brain ontogeny in mouse.

Adenosine kinase deficiency: Three new cases and diagnostic value of hypermethioninemia.

Adenosine kinase (ADK) deficiency is characterized by liver disease, dysmorphic features, epilepsy and developmental delay. This defect disrupts the adenosine/AMP futile cycle and interferes with the upstream methionine cycle. We report the clinical, histological and biochemical courses of three ADK children carrying two new mutations and presenting with neonatal cholestasis and neurological disorders.

[An acidosis not so basic].

We present the case of a four-year-old girl, who was hospitalized in intensive care unit for a coma resulting from metabolic acidosis with increased anion gap. The patient was treated for short bowel syndrome, following necrotising enterocolitis, which occurred 51 days after birth. In our initial evaluation of the patient's metabolic acidosis, we were unable to identify the cause of the increased anion gap.

Nitrous oxide and vitamin B12 in sickle cell disease: Not a laughing situation.

Nitrous oxide (NO) is widely used as an anesthetic or an analgesic. NO prolonged and recurrent administration is known to affect vitamin B12 metabolism with subsequent clinical consequences. We report herein the case of a 13-year-old girl with sickle cell disease exhibiting severe neurological and biochemical signs of functional vitamin B12 deficiency due to prolonged and repeated exposure to NO.

Diagnostic contribution of metabolic workup for neonatal inherited metabolic disorders in the absence of expanded newborn screening.

Inherited metabolic disorders (IMDs) in neonates are a diagnostic and therapeutic challenge for the neonatologist, with the priority being to rapidly flag the treatable diseases. The objective of this study was to evaluate the contribution of targeted metabolic testing for diagnosing suspected IMDs on the basis of suggestive clinical setting or family history in neonates. We conducted an observational study over five years, from January 1st, 2010 to December 31, 2014 in the neonatal intensive care unit (NICU) at Robert Debré University Hospital, Paris, France.

SLC13A3 variants cause acute reversible leukoencephalopathy and α-ketoglutarate accumulation.

Objective: SLC13A3 encodes the plasma membrane Na /dicarboxylate cotransporter 3, which imports inside the cell 4 to 6 carbon dicarboxylates as well as N-acetylaspartate (NAA). SLC13A3 is mainly expressed in kidney, in astrocytes, and in the choroid plexus. We describe two unrelated patients presenting with acute, reversible (and recurrent in one) neurological deterioration during a febrile illness.

Long-term liver disease in methylmalonic and propionic acidemias.

Background And Objectives: Patients affected with methylmalonic acidemia (MMA) and propionic acidemia (PA) exhibit diverse long-term complications and poor outcome. Liver disease is not a reported complication. The aim of this study was to characterize and extensively evaluate long-term liver involvement in MMA and PA patients.