الفهرس 
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Abstract
Organic acidemias (OAs) are considered one of the most common inborn errors of metabolism among high-risk populations. They comprise a diverse metabolic disorders that are characterized by the buildup of toxic, acidic intermediates in body fluids and tissues with increased excretion of organic acids in urine. They are generally caused by deficits in particular enzymes involved in amino acids breakdown pathways.
The most common OAs include methylmalonic acidemia (MMA), propionic acidemia (PA), isovaleric acidemia (IVA), 3-methylcrotonylglycinuria (3-MCG), 3-methylglutaconic aciduria (3-MGA), and glutaric aciduria type 1(GA1).
Common OAs can be detected by newborn screen, or typically manifest as acute metabolic collapse in the neonatal period. The affected children may experience a period of well-being followed by a life threatening attack of metabolic acidosis with significant high anion gap. The presenting episode may demonstrate a high mortality if not treated promptly, and it may be misdiagnosed as sepsis with multi-system organ failure.
In order to reach a precise diagnosis, a diagnostic approach has to be followed, including a thorough history, a comprehensive physical examination and rational plan of investigation should be in place.
The current study is a descriptive retrospective study that aimed to:
1- Evaluate the spectrum of common OAs among pediatrics aged group followed up at the Metabolic Clinic, Medical Genetics Department, Faculty of Medicine, Ain Shams University Hospitals, in the period from January 2017 to January 2022.
2- Present different clinical and biochemical characterizations and the time of onset of these disorders so that helps in raising the high index of suspicion among pediatricians and health care practitioners to make an early diagnosis.
Our study included 70 confirmed Egyptian patients with common OAs that were categorized into 4 groups; MMA, PA, IVA, and GA1.
Regarding the sociodemographic characteristics of the studied patients, they were 40 males (57.1%) and 30 females (42.9%), with more residence in Greater Cairo (55.7%), among them 68 (97.1%) were full term, and 2 (2.9%) were preterm. Their ages ranged between 1.6 and 14.9 years, with a median age of 5.9 years at the time of the study; a median age at the onset of the symptoms of 150 days; and a median age at diagnosis of 13 months. As regards the family history, parental consanguinity was observed in 57 cases (81.4%), sibling affection and mortality was identified in 19 cases (27.1%), 33 cases (47.1%), respectively.
As regards the disease frequency, GA1 was the most frequent disorder, where it was observed in 27 cases (38.6%), followed by MMA in 25 cases (35.7%), IVA in 10 cases (14.3%), and PA in 8 cases (11.4%)
As regards the presenting symptoms and signs of the studied patients, poor feeding was the most frequent presenting symptom, where it was detected in 68.6% (48/70) of patients, followed by delayed development in 60% (42/70), then, vomiting in 54.3% (38/70), hypotonia in 41.4% (29/70), and changing of head size in 40% (28/70) of patients.
As regards the presenting symptoms and signs among different groups of the studied patients, our results revealed that poor feeding was the most frequent presenting symptom in MMA, PA, and IVA, where it was detected in 84% (21/25), 87.5% (7/8), and 90% (9/10) of patients, respectively. Whereas, delayed development was the most frequent presenting symptom in GA1, where it was detected in 92.6% (25/27) of patients.
As regards the presenting clinical characteristics among different groups of the studied patients, our present study reported hypotonia in 44% (11/25) of MMA patients, 62.5% (5/8) of PA patients, and (3/10) 30% of IVA patients, whereas hypertonia and dystonia were detected in 53.6% (15/27) and 70.3% (19/27) of GA1 patients, respectively.
As regards the available presenting laboratory findings of the studied patients, our study demonstrated that anemia was the most frequent presenting laboratory abnormality, where it was detected in 73% (46/63) of patients.
Regarding the presenting laboratory metabolic assessment, abnormal plasma acylcarnitine profile and abnormal urinary organic acids was detected in 100% of the studied patients, while Acidosis was detected in 56% (14/25) of MMA, 75% (6/8) of PA patients and 30% (3/10) of IVA patients, in addition, hyperammonemia was observed in 88% (22/25) of MMA, 87.5% (7/8) of PA patients, 30% (3/10) 0f IVA patients. Whereas, none of GA1 patients showed acidosis or hyperammonemia.
As regards the presenting plasma acylcarnitine profile and UOAs among different groups of the studied patients, our results demonstrated that all MMA patients showed elevated plasma C3 and increased urinary methylmalonic acid, methylcitric acid, and 3-hydroxy propionic acid; all PA patients showed elevated plasma C3 and increased urinary methylcitric acid, 3-hydroxy propionic acid, and propionylglycine; all IVA patients showed elevated plasma C5 and increased urinary isovalerylglycine, 3-hydroxyisovaleric acid; and all GA1 patients showed elevated plasma C5DC and increased urinary glutaric acid, 3-hydroxyglutaric acid.
Regarding the main documented complications among the studied patients during the study period, our results showed that delayed psychomotor development was the most frequent complication in all the studied patients, which was observed mainly in the form of delayed motor development, where it was detected in 65.7% (46/70); speech delay in 24.3% (17/70) of the patients; and mental delay in 8.6% (6/70) of the patients. Additionally, other documented complications were in the form of visual impairment in 25% (6/24) of the patients; impaired renal function in 8.6% (3/35) of the patients; joint contracture in 33.3% (9/27) of the patients; blood cytopenia(s) in 12% (3/25) of the patients; and faltering growth in 19.2% (10/52) of the patients.
Regarding the main complications among different groups during the study period, MMA patients showed delayed psychomotor development in the form of motor delay, which was detected in 44% (11/25); speech delay in 16% (4/25); and mental delay in 20% (5/25) of the patients. PA patients showed only developmental delay in the form of motor delay, where it was detected in 87.5% (7/8), and speech delay in 12.5% (1/8). IVA patients showed developmental delay mainly in the form of motor delay, where it was detected in 20% (2/10) of patients, and mental delay in 10% (1/10) of patients, in addition to impaired renal function that was detected in 10% (1/10) of patients. GA1 patients showed developmental delay mainly in the form of motor delay, where it was detected in 96.3% (26/27); and speech delay in 44.4% (12/27) of patients, as well as, joint contracture and faltering growth in 33.3% (9/27) and 33.3% (9/27) of patients, respectively.
As regards disease course and patient outcome, IVA showed the best disease course and patient outcome, where all of the IVA patients were alive and showed a regressive course, followed by MMA, which showed a regressive course in 84% (21/25) of patients and a mortality rate of 4% (1/25) of patients. Regarding PA, although it showed a regressive course in 75% (6/8) of patients, PA patients showed the worst outcome, where the mortality rate was 25% (2/8) of the patients. On the other hand, GA1 had the worst disease course, where a regressive course was detected in only 7.4% (2/27) of patients, while GA1 patients showed a low mortality rate of 4.2% (1/24) of patients.
Our study emphasizes and confirms the previous results of the high incidence of common OAs in Egypt, and urges the health care administration in the country to develop a long-term strategic plan for the prevention of such disorders.
It is very important to consider common OAs among all children when they present any suspicious symptoms or signs that do not respond to conventional treatment.