Five years of screening for galactosaemia in South Africa: Pitfalls of using Benedict's test and thin layer chromatography to screen for galactosaemia in a developing country.

BACKGROUND: The objective of the study was to investigate the effectiveness of screening for hereditary galactosaemia with Benedict's test and thin layer chromatography (TLC) in a tertiary laboratory from a developing country. METHODS: We retrospectively analysed the results of tests done in suspected galactosaemia patients including Benedict's test, thin layer chromatography, GALT activity and DNA analysis. RESULTS: 878 paediatric patients were screened with Benedict's test; the age range was 5 days to 19 years. 48% tested positive/trace on the Benedict's test of which 52% of these had galactosuria evident on TLC. 22% of this sample had pathologically low GALT results on follow-up. 8 patients from the screened population were confirmed to have galactosaemia, in addition to 6 more patients diagnosed with galactosaemia without screening tests performed. Median ages at which the diagnoses were made in the screened and non-screened samples were 2 months and 6 months respectively. Confirmatory DNA testing was performed in 2 patients, whom were found to be heterozygous for S135L mutation. CONCLUSION: Inadequate performance of Benedict's test and TLC was demonstrated by false positive and false negative results leading us to conclude that screening test results require interpretation with caution.

Mevalonate kinase deficiency masked by cytomegalovirus infection and obscure liver disease.

BACKGROUND: Chronic liver disease with conjugated hyperbilirubinaemia and failure to thrive can have multifactorial aetiologies. Investigations can be complex and difficult especially when obscured by a viral infection affecting liver function. METHODS: A 5 month old male infant was referred for investigation of chronic liver disease and a history of jaundice with multiple febrile episodes. Liver function tests were performed followed by a liver biopsy and microbiological workup for infectious disease. In addition, urine analysis of organic acids was also performed. RESULTS: There was marked conjugated hyperbilirubinaemia with markedly elevated hepatocellular enzymes and normal ductal enzymes. Proteinuria and near normal renal function suggested early renal impairment. There was also leukocytosis and bicytopenia. An extensive bacteriological investigation including TB workup was negative. CMV infection was confirmed by viral load and antibody reactivity. There was prolonged PT and PTT and high INR. The liver biopsy showed giant cell transformation of hepatocytes with mild cholestasis, portal and peri-cellular fibrosis with alpha-1-antitrypsin positive granules in the hepatocyte cytoplasm suggesting alpha-1-antitrypsin deficiency. Urine organic acids revealed significantly elevated mevalonolactone. CONCLUSIONS: We confirmed the genetic diagnosis of mevalonic aciduria caused by MVK deficiency which had been masked by liver disease and the possible misdiagnosis of alpha-1-antitrypsin deficiency.

Case Report: A Toddler With Anasarca Caused by Congenital Nephrotic Syndrome.

Congenital nephrotic syndrome is a rare inherited disorder arising from defects in the proteins of the cells in the glomerular basement membrane and develops either in utero or at birth. The clinical presentation is the result of massive protein loss in the urine with associated compensatory mechanisms. Here we present a clinical case of a female toddler with a history of anasarca (severe generalised edema) from birth and who presents with the classical biochemical laboratory findings of nephrotic syndrome, together with the more pronounced features that arise from protein loss including abnormal thyroid function testing and a marked hypercholesterolaemia. Renal biopsy indicated congenital nephrotic syndrome of the Finnish type. This clinical-diagnostic case report represents an example of the broad spectrum of pathophysiological findings of a severe congenital nephrotic syndrome.