Clinico-Radiological Correlation in 26 Egyptian Children with Glutaric Acidemia Type 1.

BACKGROUND: Glutaric acidemia type 1 (GA1) is an inherited neurometabolic disease with significant morbidity. However, neuro-radiological correlation is not completely understood. OBJECTIVE: The study aimed to characterize the neuroimaging findings and their association with neurological phenotype in GA1 children. METHODS: Twenty-six Egyptian children (median age = 12 months) diagnosed with GA1 underwent clinical evaluation and brain magnetic resonance imaging (MRI). We objectively assessed the severity of neurological phenotype at the time of MRI using movement disorder (MD) and morbidity scores. Evaluation of brain MRI abnormalities followed a systematic and region-specific scoring approach. Brain MRI findings and scores were correlated with MD and morbidity scores, disease onset, and presence of seizures. RESULTS: Fifteen (57.7%) cases had insidious onset, eight (30.8%) manifested acute onset, whereas three (11.5%) were asymptomatic. Ten (38.5%) cases had seizures, five of which had no acute encephalopathic crisis. Putamen and caudate abnormalities (found in all acute onset, 93.3 and 73.3% of insidious onset, and one of three asymptomatic cases) were significantly related to MD (p = 0.007 and 0.013) and morbidity (p = 0.005 and 0.003) scores. Globus pallidus abnormalities (50% of acute onset, 46.7% of insidious onset, and one of three of asymptomatic cases) were significantly associated with morbidity score (p = 0.023). Other MRI brain abnormalities as well as gray and white matter score showed no significant association with neurological phenotype. Younger age at onset, acute onset, and seizures were significantly associated with worse neurological manifestations. CONCLUSION: Patients with GA1 manifest characteristic and region-specific brain MRI abnormalities, but only striatal affection appears to correlate with neurological phenotype.

Selective screening for inborn errors of metabolism by tandem mass spectrometry at Sohag University Hospital, Egypt.

BACKGROUND: Inborn errors of metabolism (IEMs) comprise a group of inherited diseases that can have devastating consequences and cause irreversible damage to different body systems and even lead to death. Newborn screening helps in the presymptomatic diagnosis of many medical disorders including IEMs. Early diagnosis and management of IEMs helps reduce morbidity and mortality. OBJECTIVE: This study aimed to estimate the prevalence of IEMs among at-risk children and contribute toward early diagnosis and management in order to minimize morbidity and mortality. METHODS: This prospective study was conducted at the Pediatrics and Neonatology Department, Sohag University Hospital, Egypt. The study enrolled 308 participants suspected of having IEMs. Cases were included based on the presence of any of the following: unexplained convulsions, persistent metabolic acidosis, persistent hypoglycemia, disturbed consciousness, delayed milestones, or family history of previous sibling death with IEMs or sibling death with a history suggestive of IEMs. All participants in the study were subjected to metabolic screening by tandem mass spectrometry (MS/MS). RESULTS: Out of 308 neonates, 93 (30.2%) were diagnosed with IEMs. The most common diagnosis was phenylketonuria, followed by glutaric aciduria type 1 and maple syrup urine disease (43%, 19.4%, and 14%, respectively). Five patients had Canavan disease, four had medium-chain acyl CoA dehydrogenase deficiency, three had congenital lactic acidosis, two had methylmalonic acidemia, and two had primary carnitine deficiency. Propionic acidemia, isovaleric acidemia, homocystinuria, short-chain acyl CoA dehydrogenase deficiency, B-ketothiolase deficiency, and ketone body utilization defect were diagnosed in one patient each. Most patients improved (73.1%) following proper specific management. CONCLUSION: We recommend newborn screening for IEMs using MS/MS, which may help with the early diagnosis and management of this group of disorders.

Characterization and outcome of 11 children with non-diabetic ketoacidosis.

OBJECTIVES: To study the clinical and laboratory features, management, and outcome of pediatric non-diabetic ketoacidosis (NDKA). METHODS: Between May 2018 and April 2020, we prospectively collected children under 18 years who presented with ketoacidosis, defined as ketosis (urinary ketones ≥++ and/or serum ß-hydroxybutyrate level ≥3 mmol/L) and metabolic acidosis (pH <7.3 and HCO3 - <15 mmol/L). Children with HbA1c level ≥6.5% at initial presentation and those meeting the diagnostic criteria for DM during follow-up were excluded. Data were collected on demographics, clinical and laboratory features, management, and outcome. RESULTS: Eleven children with 19 episodes of NDKA were identified. The median age was 12 months (range from 5 months to 5 years). They manifested dehydration and disturbed conscious level (all cases), convulsions (n=6), hypoglycemia (n=6), hyperglycemia (n=2) and significant hyperammonemia (n=4). Most cases required intensive care management. Death or neurodevelopmental impairment occurred in six cases. Seven cases had inborn errors of metabolism (IEMs). Other cases were attributed to starvation, sepsis, and salicylate intoxication. CONCLUSIONS: This is the largest case series of pediatric NDKA. Ketoacidosis, even with hyperglycemia, is not always secondary to diabetes mellitus. IEMs may constitute a significant portion of pediatric NDKA. Increased awareness of this unfamiliar condition is important for prompt diagnosis, timely management, and better outcome.

The clinico-radiological findings of MSUD in a group of Egyptian children: Contribution to early diagnosis and outcome.

BACKGROUND: Maple syrup urine disease (MSUD) is an autosomal recessive inborn error of amino acid metabolism, with unique clinico-radiological findings. This study aims to show the benefit of using the clinico-radiological findings for early diagnosis of children with MSUD, and confirming this diagnosis using the tandem mass spectrometry (MS/MS), in order to avoid deleterious outcome. METHODS: A prospective cohort study conducted in the period from August 2016 to December 2020. Twenty-one children were included either by selective screening or by high-risk screening. All children had clinical and neurodevelopmental evaluation, brain magnetic resonance imaging (MRI) assessment, and blood amino acids analysis at diagnosis. Patients were followed clinically. RESULTS: Most children had acute onsets neuro-developmental symptoms, with wide range of brain parenchyma involvement on MRI (hyperintensity). Diagnosis of MSUD was confirmed by detecting high serum levels of leucine/isoleucine (mean value 2085.5 µmol/L) in all patients, and elevated levels of serum valine in (81%) of children. In addition, all children showed elevated leucine: alanine ratio, and leucine: phenylalanine ratio. CONCLUSIONS: The characteristic clinico-radiological features can help in the early diagnosis of MSUD children, thus preventing the delay in laboratory diagnosis and improving their outcomes.

Propionic and Methylmalonic Acidemias: Initial Clinical and Biochemical Presentation.

PA and MAA have numerous nonspecific presentations, potentially leading to delayed diagnosis or misdiagnosis. In this paper, we present the clinical and biochemical characteristics of MMA and PA patients at initial presentation. Results. This is a retrospective review of 20 patients with PA (n = 10) and MMA (n = 10). The most observed symptoms were vomiting (85%) and refusing feeding (70%). Ammonia was 108.75 ± 9.3 µmol/l, showing a negative correlation with pH and bicarbonate and positive correlation with lactate and anion gap. Peak ammonia did not correlate with age of onset (r = 0.11 and p = 0.64) or age at diagnosis (r = 0.39 and p = 0.089), nor did pH (r = 0.01, p = 0.96; r = -0.25, p = 0.28) or bicarbonate (r = 0.07, p = 0.76; r = -0.22, p = 0.34). There was no correlation between ammonia and C3 : C2 (r = 0.1 and p = 0.96) or C3 (r = 0.23 and p = 0.32). The glycine was 386 ± 167.1 µmol/l, and it was higher in PA (p = 0.003). There was a positive correlation between glycine and both pH (r = 0.56 and p = 0.01) and HCO3 (r = 0.49 and p = 0.026). There was no correlation between glycine and ammonia (r = -0.435 and p = 0.055) or lactate (r = 0.32 and p = 0.160). Conclusion. Clinical presentation of PA and MMA is nonspecific, though vomiting and refusing feeding are potential markers of decompensation. Blood gas, lactate, and ammonia levels are also good predictors of decompensation, though increasing levels of glycine may not indicate metabolic instability.