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

Abstract

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

Clinical, molecular, and genetic evaluation of galactosemia in Turkish children

“…The ages at the time of diagnosis were examined in many studies, and patients who were diagnosed in the first 15 days were defined as early diagnosed (8)(9)(10)(11)(12). In our study, six of our patients were diagnosed in the first 15 days after birth and the remaining eight patients were diagnosed after 15 days.…”

“…In the study conducted by Karadağ et al (8), it was reported that the mean age at the time of hospital presentation was 13 days. Henderson et al (9) reported that 17 patients were diagnosed over a period of 21 years in the region of Cape Town in South Africa, the mean age at the time of diagnosis was 5.1 months. In the study conducted by Krantz et al (10) with 148 patients between 1955 and 1995 in Germany, the rate of early diagnosis was reported as 57.8%.…”

A De Novo Variant in Galactose-1-P Uridylyltransferase (GALT) Leading to Classic Galactosemia

“…The mutation c.855G>T (p.K285N) accounts for a majority of CG patient alleles in Eastern Europe (Lukac-Bajalo et al 2007). Finally, c.404C>T (p.S135L) accounts for a majority of CG patient alleles in parts of Africa (Henderson et al 2002). Other mutations, such as c.584T>C (p.L195P), are less common, accounting for only a small percentage of reported patient alleles, and yet others are "private" -reported only in one affected patient or family.…”

Galactosemia – North Indian Experience

“…Heterozygous are carrier because they inherit one normal gene and one defective gene. (4) Narendra Rathi et al observed that three congenital disorders are related to galactose metabolism -a) type one galactosemia (classic galactosemia) -deficiency of GALT (galactose -1-phosphate uridyl transferase) b) type two galactosemia -deficiency of galactokinase. It solely presents with cataract .…”