Research article

The clinical and molecular spectrum of galactosemia in patients from the Cape Town region of South Africa

Howard Henderson¹ , Felicity Leisegang¹ , Ruth Brown¹ and Brian Eley²

¹  Department of Chemical Pathology and School of Child and Adolescent Health, Red Cross Children's Hospital, University of Cape Town, Cape Town, South Africa

²  Dept of Pediatrics, and School of Child and Adolescent Health, Red Cross Children's Hospital, University of Cape Town, Cape Town, South Africa

author email corresponding author email

BMC Pediatrics 2002, 2:7doi:10.1186/1471-2431-2-7

Published:	2 September 2002

Abstract

Background

The objective of this study was to document the clinical, laboratory and genetic features of galactosemia in patients from the Cape Town metropolitan region.

Methods

Diagnoses were based on thin layer chromatography for galactosuria/galactosemia and assays of erythrocyte galactose-1-phosphate uridyltransferase (GALT) and galactokinase activities. Patients were screened for the common S135L and Q188R transferase gene mutations, using PCR-based assays. Screening for the S135L mutation in black newborns was used to estimate the carrier rate for galactosemia in black South Africans.

Results

A positive diagnosis of galactosemia was made in 17 patients between the years 1980 to 2001. All had very low or absent galactose-1-phosphate uridyltransferase (GALT) activity, and normal galactokinase levels. The mean age at diagnosis was 5.1 months (range 4 days to 6.5 months). A review of 9 patients showed that hepatomegaly (9/9), and splenomegaly, failure to thrive, developmental delay, bilateral cataracts (6/9) were the most frequent features at diagnosis. Six had conjugated hyperbilirubinemia. Four experienced invasive E. coli infection before diagnosis. Ten patients were submitted to DNA analysis. All 4 black patients and 2 of mixed extraction were homozygous for the S135L allele, while all 3 white patients were homozygous for the Q188R allele. The remaining patient of mixed extraction was heterozygous for the Q188R allele. The estimated carrier frequency of the S135L mutation in 725 healthy black newborns was 1/60.

Conclusions

In the absence of newborn screening the delay in diagnosis is most often unacceptably long. Also, carrier frequency data predict a galactosemia incidence of approximately 1/14 400 for black newborns in the Cape Metropole, which is much higher than the current detection rate. It is thus likely that many patients go undetected.