Diagnostic challenges of aminoacidopathies and organic acidemias in a developing country: a twelve-year experience

Abstract

Background: Diagnosis of aminoacidopathies and organic acidemias constitutes a real challenge in a developing country with high consanguinity rate and no systematic newborn screening. We report a twelve-year experience with the identification of these disorders in Lebanon, based on their clinical and biochemical profiles.

Methods: In this retrospective study, we reviewed clinical presentation and biochemical investigations of 294 patients. Traditional chromatographic methods were used for analyses. Findings were linked to the identified disorders.

Results: Out of 2921 patients, presenting to our metabolic program with neurological, digestive, family history and/or other symptoms suggestive of aminoacidopathy or organic acidemia, 294 patients were included with confirmed amino or organic acid disorder. The overall analytical yield was 10%. Aminoacidopathies were three-fold higher than organic acidemias. Phenylketonuria and methylmalonic acidemia were the most frequent. The majority of patients (79%) were symptomatic (median age: 14months, range: 1day-44years), mainly with neurological manifestations (87%). Intellectual disability was mostly due to phenylketonuria (73%). Chronic liver failure was frequent in maple syrup urine disease (53%). Plasma amino and urine organic acid chromatography were diagnostic in 8.8% and 3.9% of analyzed cases, respectively. Change in chromatographic technique from reversed-phase to ion-exchange enhanced the detection of many aminoacidopathies.

Conclusions: In the absence of newborn screening, the majority of aminoacidopathy and organic acidemia cases are still diagnosed clinically. This study emphasizes the importance of clinical awareness and accurate biochemical analyses as key tools for diagnosis in countries like ours, and the necessity for a comprehensive national newborn screening program.

Keywords: 2-hydroxyglutaric aciduria; 2HGA; 6-PTS; 6-pyruvoyl- tetrahydrobiopterin synthase; AA; AUBMC; American University of Beirut Medical Center; Amino acid chromatography; Aminoacidopathies; CSF; Cb1 a–d; Cb1 b; D; DHPR; GA II; GC/MS; GTP; HCY; HPLC; IEM; Inborn errors of metabolism; M; MMA; MS/MS; MSUD; NBS; Newborn screening; OA; OTC; Organic acid chromatography; Organic acidemias; PA; PKU; Saint Joseph University; UCD; UPLC; USJ; Y; aminoacidopathies; cerebrospinal fluid (CSF); cobalamin a–d deficiency; cobalamin b deficiency; days; dihydropteridine reductase; gas chromatography mass spectrometry; glutaric aciduria type II; guanosine 5 triphosphate cyclohydrolase; high performance liquid chromatography; homocystinuria; inborn errors of metabolism; maple syrup urine disease; methylmalonic acidemia; months; newborn screening; organic acidemias; ornithine transcarbamylase; phenylketonuria; propionic acidemia; tandem mass spectrometry; ultra performance liquid chromatography; urea cycle defects; years.