TY - JOUR
T1 - A Multinational Study of Acute and Long-term Outcomes of Type 1 Galactosemia Patients Who Carry the S135L (c.404C>T) Variant of GALT
AU - Katler, Quinton
AU - Stepien, Karolina M
AU - Paull, Nathan
AU - Patel, Sneh
AU - Adams, Michael
AU - Balci, Mehmet Cihan
AU - Berry, Gerard T
AU - Bosch, Annet M
AU - De La O, Angela
AU - Demirbas, Didem
AU - Edman, Julianna
AU - Ficicioglu, Can
AU - Goff, Melanie
AU - Hacker, Stephanie
AU - Knerr, Ina
AU - Lancaster, Kristen
AU - Li, Hong
AU - Mendelsohn, Bryce A
AU - Nichols, Brandi
AU - de Rezende Pinto, Wladimir Bocca Vieira
AU - Rocha, Júlio César
AU - Rubio-Gozalbo, M Estela
AU - Saad-Naguib, Michael
AU - Scholl-Buergi, Sabine
AU - Searcy, Sarah
AU - de Souza, Paulo Victor Sgobbi
AU - Wittenauer, Angela
AU - Fridovich-Keil, Judith L
N1 - This article is protected by copyright. All rights reserved.
PY - 2022/11
Y1 - 2022/11
N2 - Patients with galactosemia who carry the S135L (c.404C>T) variant of GALT, documented to encode low-level residual GALT activity, have been under-represented in most prior studies of outcomes in Type 1 galactosemia. What is known about the acute and long-term outcomes of these patients, therefore, is based on very limited data. Here, we present a study comparing acute and long-term outcomes of 12 patients homozygous for S135L, 25 patients compound heterozygous for S135L, and 105 patients homozygous for two GALT-null (G) alleles. This is the largest cohort of S135L patients characterized to date. Acute disease following milk exposure in the newborn period was common among patients in all 3 comparison groups in our study, as were long-term complications in the domains of speech, cognition, and motor outcomes. In contrast, while at least 80% of both GALT-null and S135L compound heterozygous girls and women showed evidence of an adverse ovarian outcome, prevalence was only 25% among S135L homozygotes. Further, all young women in this study with even one copy of S135L achieved spontaneous menarche; this is true for only about 33% of women with classic galactosemia. Overall, we observed that while most long-term outcomes trended milder among groups of patients with even one copy of S135L, many individual patients, either homozygous or compound heterozygous for S135L, nonetheless experienced long-term outcomes that were not mild. This was true despite detection by newborn screening and both early and life-long dietary restriction of galactose. This information should empower more evidence-based counseling for galactosemia patients with S135L. This article is protected by copyright. All rights reserved.
AB - Patients with galactosemia who carry the S135L (c.404C>T) variant of GALT, documented to encode low-level residual GALT activity, have been under-represented in most prior studies of outcomes in Type 1 galactosemia. What is known about the acute and long-term outcomes of these patients, therefore, is based on very limited data. Here, we present a study comparing acute and long-term outcomes of 12 patients homozygous for S135L, 25 patients compound heterozygous for S135L, and 105 patients homozygous for two GALT-null (G) alleles. This is the largest cohort of S135L patients characterized to date. Acute disease following milk exposure in the newborn period was common among patients in all 3 comparison groups in our study, as were long-term complications in the domains of speech, cognition, and motor outcomes. In contrast, while at least 80% of both GALT-null and S135L compound heterozygous girls and women showed evidence of an adverse ovarian outcome, prevalence was only 25% among S135L homozygotes. Further, all young women in this study with even one copy of S135L achieved spontaneous menarche; this is true for only about 33% of women with classic galactosemia. Overall, we observed that while most long-term outcomes trended milder among groups of patients with even one copy of S135L, many individual patients, either homozygous or compound heterozygous for S135L, nonetheless experienced long-term outcomes that were not mild. This was true despite detection by newborn screening and both early and life-long dietary restriction of galactose. This information should empower more evidence-based counseling for galactosemia patients with S135L. This article is protected by copyright. All rights reserved.
U2 - 10.1002/jimd.12556
DO - 10.1002/jimd.12556
M3 - Article
C2 - 36093991
SN - 0141-8955
VL - 45
SP - 1106
EP - 1117
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
IS - 6
ER -