Related Experiment Videos
Congenital lactic acidosis in children--differential diagnosis in 44 cases
E Pronicka1, B Gruszczyńska, B Badurska
1Child Health Centre, Warszawa, Poland.
Insights
This study details the differential diagnosis of lactic acidosis in 44 children, identifying specific causes like glycogenosis and mitochondrial disorders through advanced biochemical and genetic testing.
Area of Science:
- Pediatric Medicine
- Biochemistry
- Genetics
Background:
- Lactic acidosis in children presents with diverse clinical symptoms, complicating diagnosis.
- Accurate diagnosis is crucial for effective management and treatment of pediatric metabolic disorders.
Purpose of the Study:
- To perform differential diagnosis of lactic acidosis in 44 children aged 2 weeks to 4 years.
- To categorize patients based on clinical manifestations: hepatomegaly/hypoglycemia, ataxia/developmental delay, or intellectual disability/hypotonia.
- To identify the underlying causes of congenital lactic acidosis using a comprehensive diagnostic approach.
Main Methods:
- Clinical assessment and categorization into three groups based on symptoms.
- Biochemical analyses including glucose and alanine loading tests.
- Cerebrospinal fluid lactate levels, urinary organic acid analysis (GC-MS), muscle biopsy, and liver enzyme assays.
Main Results:
- Group I (hepatomegaly/hypoglycemia) revealed various types of glycogenosis and fructose-1,6-diphosphatase deficiency.
- Group II (ataxia/developmental delay) suggested Leigh's syndrome with impaired glucose formation from alanine and elevated CSF lactate.
- Group III (intellectual disability/hypotonia) identified mitochondrial disorders, 3-hydroxy-3-methylglutaric acidosis, and secondary lactate increases.
Conclusions:
- A combination of clinical evaluation, biochemical tests, and advanced molecular diagnostics is effective for differential diagnosis of congenital lactic acidosis in children.
- The study highlights the importance of a multi-faceted approach to uncover the etiology of pediatric lactic acidosis.
- Early and accurate diagnosis facilitates timely intervention and improves patient outcomes.
Abstract:
The purpose of the study was differential diagnosis of lactic acidosis in 44 children aged from 2 weeks to 4 years. In all of them the lactate level in repeated determinations exceeded 27 mg/100 ml. From the point of view of clinical manifestations the children were divided into three groups: 26 with hepatomegaly and hypoglycaemia (I), 6 with ataxia and retardation of somatic development (II), 12 with mental retardation and muscular hypotonia (III). Together with basic biochemical studies other tests were done, if necessary, including glucose and alanine loading, lactate determination in cerebrospinal fluid, analysis of urinary organic acids by the GC-MS method, morphological examinations of muscle biopsy material, enzymatic determinations in liver biopsy material. In group I glycogenosis was suspected and its type was finally established after biochemical and enzymatic tests (types I, Ib, III, VI, VIa, XI). In one case fructose-1,6-diphosphatase deficiency was suspected. In group II the clinical manifestations resembled Leigh's syndrome. The tests demonstrated an inhibition of glucose formation from alanine, and lactate level in the cerebrospinal fluid was evidently raised above that in the serum. Gasometric index showed the presence of respiratory alkalosis with metabolic compensation rather than primary lactate acidosis. In group III, with considerable clinical variety of signs, in only nine out of 12 children the cause of lactate acidosis could have been established (pathological changes of mitochondria in 4 cases, secondary increase of lactate without pathogenetic importance in 4, and 3-hydroxy-3-methylglutaric acidosis in 1 case. In conclusion it is thought that this combination of diagnostic methods is useful in differential diagnosis of congenital lactate acidosis in children.