Clinical And Laboratory Studies In Organic Aciduria

ObjectiveOrganic aciduria, also called organic acidemia, is the most frequent inherited metabolic disease among children. So far, more than 50 types of organic acidemias have been found. With complicated and diverse clinical manifestations, most of organic acidemias impair the nervous system seriously and bring heavy burden to the family and society. GC/MS is a very useful method for the screening and diagnosis for organic acidemias. Early diagnosis and adequate treatment contribute a lot to improve the neurological prognosis of the patients. However, due to constraints, we can not present a comprehensive screening of organic acidurias, so getting familiar with the clinical and laboratory characteristics of organic acidurias is premise and key to the timely GC/MS, early diagnosis and proper treatment, so as to lay the foundation of reducing the disability rate of children and also improving life quality.MethodsA total of 35 cases of organic aciduria children (including 26 cases of methyl-malonic aciduria,5 cases of glutaric aciduria type I and 4 cases of propionic acidemia) were analyzed with a series of clinical characteristics including onset age, type of onset, clinical manifestations, family history, past history, diagnosis and differential diagnosis, treatment and prognosis; Also biochemistry examination, urinary organic acids detected by gas chromatography/mass spectrometry(GC/MS), imaging, EEG and BAEP were analyzed.Results1.22 cases of children precipitated before first year of life, and the average onset age is 8 months.2.28 patients had gone through acute onset,24 cases of which had infection or high-protein diet before onset.3. The main clinical manifestations are:psychomotor development or mental retardation (n=26), psychomotor development back(n=5), a history of intermittent vomiting(n=18), feeding difficulties (n=16), seizures (n=12), shortness of breath (n=9), attacks of drowsiness (n=8), pale (n=8), muscle tension reducing(n=8), muscular hypertonia (n=7), malnutrition(n=6), disturbance of consciousness(n=6), ataxia(n=5), extrapyramidal symptoms(n=5), abnormal bigness of the head in 5 cases (all of them are glutaric aciduria type I), gastrointestinal bleeding (n=3) and paralysis(n=2).4.18 cases of children were once diagnosed as"gastroenteritis, pancreatitis, dehydration, hydrocephalus, encephalitis, cerebral palsy or arachnoid cyst" by local hospitals.5. Mothers of 12 patients had unexplained miscarriage, stillbirth history, siblings death history psychomotor retardation, or family history of mental retardation and other abnormalities.6. Laboratory examination:the urinary organic acids of all patients analyzed by gas chromatography/mass spectrometry were presented abnormalities. Abnormal biochemistry examination including:metabolic acidosis (n=25), anemia(n=12), lactic acid increased (n=11), liver dysfunction (n=10). hyperammonemia (n=6), renal dysfunction (n=6), neutropenia (n=5), thrombocytopenia(n=4). Abnormal cranial MRI examination of 30 cases including:brain extracellular space widened (n=28), ventricles widened (n=24), delayed myelination (n=16), abnormal signal in basal ganglia (n=12), subdural effusion (n=6), intracranial bleeding (n=3). The EEG showed that a 25 of total presented slow activity.spike and slowly discharge. The BAEP showed that 9 cases in 20 presented abnormalities in section of the peripheral or brain stem, and increased hearing threshold.7. Treatment and prognosis:during the acute phase, improving the internal environment, guaranteeing the heat, controlling infection and convulsions are essential.30 cases of children, followed up for 1 month to 5 years, accepted long-term treatment including the low-protein diet, carnitine, vitamin B2, vitamin B12 treatment,18 cases showed significant improvement in psychomotor development; 3 cases are still with convulsion; 1 patient died and 5 cases withdrew. ConclusionWith complicated and diverse clinical manifestations, most patients of organic acidemias have acute onset with inducements of infection and high-protein diet. The clinical and laboratory features of organic acidemias are psychomotor retardation or regression, vomiting, feeding difficulties, abnormal muscle tone, convulsions, extrapyramidal symptoms, metabolic acidosis, hyperammonemia, abnormal liver function, anemia etc. Organic acidemia can cause serious neurological damage. Cephalometry and blood biochemical tests can provide valuable diagnostic clues,, those who had unknown-reasoned intellectual and movement disorders, seizures and metabolic abnormalities shall be carried GC/MS examination of urine organic acids early. Early diagnosis and adequate treatment contribute a lot to improve the neurological prognosis of the patients.