OBJECTIVES: The newborn screening (NBS) program in the Republic of Serbia has several decades of tradition, but it has not included any organic acidemias (OA). Therefore, this study aimed to establish the cut-offs of the corresponding NBS markers in the population of healthy newborns. METHODS: In dried blood samples (DBS) collected from 1,771 healthy newborns, we analyzed levels of propionylcarnitine (C3), isovalerylcarnitine (C5), and glutarylcarnitine (C5DC) using tandem mass spectrometry. Further we calculated the following ratios: C3/acetylcarnitine (C3/C2), C3/palmitoylcarnitine (C3/C16), C5/ free carnitine (C0), C5/C2, C5/C3, C5DC/octanoylcarnitine (C8), and C5DC/C0. RESULTS: The cut-offs for methylmalonic acidemia (MMA) or propionic acidemia (PA) were C3>5.73 μmol/L, C3/C2>0.23, and C3/C16>2.36. Based on the study findings, the screening results indicative for isovaleric acidemia (IVA) would include C5>0.372 μmol/L, C5/C0>0.020, C5/C2>0.019, and C5/C3>0.31. Finally, C5DC>0.303 μmol/L, C5DC/C8>7.1, and C5DC/C0>0.019 would justify further testing for glutaric acidemia type I (GA1). The cut-offs were satisfactorily validated via the comparison with worldwide estimates and data for several Caucasian populations. CONCLUSIONS: The levels of the OA biomarkers in the Serbian population of healthy newborns have a distribution pattern similar to the other world populations. Therefore, the proposed cut-offs represent a reliable starting point for the future development of the OA NBS.

• MeSH
• Biomarkers MeSH
• Glutaryl-CoA Dehydrogenase deficiency   MeSH
• Isovaleryl-CoA Dehydrogenase MeSH
• Humans MeSH
• Brain Diseases, Metabolic MeSH
• Infant, Newborn MeSH
• Propionic Acidemia * diagnosis   MeSH
• Amino Acid Metabolism, Inborn Errors MeSH
• Check Tag
• Humans MeSH
• Infant, Newborn MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Serbia MeSH

Isolated methylmalonic acidaemia (MMA) and propionic acidaemia (PA) are rare inherited metabolic diseases. Six years ago, a detailed evaluation of the available evidence on diagnosis and management of these disorders has been published for the first time. The article received considerable attention, illustrating the importance of an expert panel to evaluate and compile recommendations to guide rare disease patient care. Since that time, a growing body of evidence on transplant outcomes in MMA and PA patients and use of precursor free amino acid mixtures allows for updates of the guidelines. In this article, we aim to incorporate this newly published knowledge and provide a revised version of the guidelines. The analysis was performed by a panel of multidisciplinary health care experts, who followed an updated guideline development methodology (GRADE). Hence, the full body of evidence up until autumn 2019 was re-evaluated, analysed and graded. As a result, 21 updated recommendations were compiled in a more concise paper with a focus on the existing evidence to enable well-informed decisions in the context of MMA and PA patient care.

• MeSH
• Humans MeSH
• Disease Management MeSH
• Propionic Acidemia diagnosis   therapy   MeSH
• Amino Acid Metabolism, Inborn Errors diagnosis   therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Practice Guideline MeSH

BACKGROUND: The disease course and long-term outcome of patients with organic acidurias (OAD) and urea cycle disorders (UCD) are incompletely understood. AIMS: To evaluate the complex clinical phenotype of OAD and UCD patients at different ages. RESULTS: Acquired microcephaly and movement disorders were common in OAD and UCD highlighting that the brain is the major organ involved in these diseases. Cardiomyopathy [methylmalonic (MMA) and propionic aciduria (PA)], prolonged QTc interval (PA), optic nerve atrophy [MMA, isovaleric aciduria (IVA)], pancytopenia (PA), and macrocephaly [glutaric aciduria type 1 (GA1)] were exclusively found in OAD patients, whereas hepatic involvement was more frequent in UCD patients, in particular in argininosuccinate lyase (ASL) deficiency. Chronic renal failure was often found in MMA, with highest frequency in mut(0) patients. Unexpectedly, chronic renal failure was also observed in adolescent and adult patients with GA1 and ASL deficiency. It had a similar frequency in patients with or without a movement disorder suggesting different pathophysiology. Thirteen patients (classic OAD: 3, UCD: 10) died during the study interval, ten of them during the initial metabolic crisis in the newborn period. Male patients with late-onset ornithine transcarbamylase deficiency were presumably overrepresented in the study population. CONCLUSIONS: Neurologic impairment is common in OAD and UCD, whereas the involvement of other organs (heart, liver, kidneys, eyes) follows a disease-specific pattern. The identification of unexpected chronic renal failure in GA1 and ASL deficiency emphasizes the importance of a systematic follow-up in patients with rare diseases.

• MeSH
• Argininosuccinic Aciduria diagnosis   MeSH
• Kidney Failure, Chronic complications   MeSH
• Child MeSH
• Adult MeSH
• Phenotype MeSH
• Glutaryl-CoA Dehydrogenase deficiency   MeSH
• Liver metabolism   MeSH
• Kaplan-Meier Estimate MeSH
• Infant MeSH
• Middle Aged MeSH
• Humans MeSH
• Brain Diseases, Metabolic diagnosis   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Ornithine Carbamoyltransferase Deficiency Disease diagnosis   MeSH
• Infant, Newborn MeSH
• Neonatal Screening MeSH
• Child, Preschool MeSH
• Propionic Acidemia diagnosis   MeSH
• Registries MeSH
• Aged MeSH
• Urea Cycle Disorders, Inborn diagnosis   MeSH
• Amino Acid Metabolism, Inborn Errors diagnosis   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Infant MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Infant, Newborn MeSH
• Child, Preschool MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Europe MeSH