Yenidoğan Döneminde Tanı Alan Organik Asidemili Hastaların Klinik, Laboratuvar Özelliklerinin ve Prognozunun Belirlenmesi
Özet
Organic acidemias are one of the most frequent inborn errors of metabolism that are symptomatic in the neonatal period. As an autosomal recessive disorder, organic acidemias are more prevalent in our country where consanguineous marriages are more frequent.
The aim of this thesis is to define the demographic, clinical and laboratory characteristics and the prognosis of neonates diagnosed with organic acidemia in our hospital. 108 neonate (70 girls, 38 boys) who were hospitalized and diagnosed with organic acidemia in Neonatology Units of Hacettepe University Faculty of Medicine between 01.01.1987-01.03.2017 were enrolled in the study. Patient data were collected retrospectively from the patient records and the hospital computer system. Eight different organic acidemia subtypes were detected. 34,4% of the patients were diagnosed with maple syrup urine disease (MSUD), 28,7% had methylmalonic acidemia (MMA), 24,1% had propionic acidemia (PA), 5,6% had isovaleric acidemia, 2,8% had HMG-CoA lyase deficiency, 2,8% had unclassified organic acidemias, 0,9% had β-ketothiolase deficiency and 0,9% had 3-methylcrotonyl-CoA carboxylase deficiency. Consanguineous marriage was detected in 89,2% of the patients, 50% had a history of sibling loss. Most of the patients were term (75%) and had normal birth weight (%93,5). Patients diagnosed with MMA had statistically significant lower birth weight (p<0,001). Median age at the time of admittance was 4 (0-29) days. Parent’s most frequent complaints were difficulty in feeding (84,3%), respiratory distress (54,6%) and decreased activity (50,9%).
At the time of admittance 61,7% of the patients were anemic, 14,9% were thrombocytopenic. When patients with MSUD, MMA and PA were compared, no significant difference was detected (p>0,05). 68,1% of the patients had metabolic acidosis. Patients diagnosed with MMA had a higher frequency of metabolic acidosis and hypocarbia, patients with MSUD had lesser acid-base imbalance (p=0,03). Hyperamonemia was more frequent in patients with MMA and severe hyperamonemia was correlated with mortality (p=0,047). Fewer patients diagnosed with MSUD had hyperamonemia (p=0,001).
The median follow up time was 5 years (1-16). 89,8% of the patients had recurrent metabolic decompansations, 47,2% were hospitalized because of infections. Pneumonia was the most frequent cause of hospitalization (39,2%). Abnormal results were detected in 64,7% of the electroencephalographies (EEG) and 63,4% of the cranial imaging studies performed. 93% of the patients evaluated by Denver II developmental screening test had global developmental delay.
Electroencephalography, cranial imaging studies, Denver II developmental screening test results, secondary chronic diseases and mortality were identified as prognostic criteria. Age, presence of hypoglycemia, leucine values of patients diagnosed with MSUD, propionylcarnitine values of patients diagnosed with PA at the time of admittance and the prognostic factors did not show a significant correlation (p>0,05). Acidosis at the time of admittance was correlated with higher mortality, higher incidence of secondary chronic diseases and EEG abnormalities (p<0,001; p=0,193; p=0,005). 38,9% of the patients had a secondary chronic disease, seizure (20%) was the most frequent comorbidity. The mortality rate of the patients diagnosed with organic acidemia during the neonatal period was 33,3%. Patients who were diagnosed between the years 2007-2017 had significantly lower mortality (p<0,011).
Since clinical and laboratory evidence of diseases during the neonatal period are non-specific it is important that organic acidemias are kept in mind while making a diferential diagnosis. With the introduction of new diagnostic and treatment modalities mortality of organic acidemias have decreased while morbidity rates stays the same. Secondary chronic diseases are still posing an important health issue. Early recognition of demographic, clinical or laboratory evidence indicating organic acidemia is fundamental for early initiation of diagnostic tests and therapy in order to decrease disease mortality and morbidity and to have better long term outcome.
