A multinational study of acute and long-term outcomes of Type 1 galactosemia patients who carry the S135L (c.404C > T) variant of GALT

Katler, Quinton; Stepien, Karolina; Paull, Nathan; Patel, Sneh; Adams, Michael; BALCI, MEHMET; Berry, Gerard; Bosch, Annet; DeLaO, Angela; Demirbas, Didem; Edman, Julianna; Ficicioglu, Can; Goff, Melanie; Hacker, Stephanie; Knerr, Ina; Lancaster, Kristen; Li, Hong; Mendelsohn, Bryce; Nichols, Brandi; Vieira de Rezende Pinto, Wladimir; Rocha, Julio; Rubio-Gozalbo, M.; Saad-Naguib, Michael; Scholl-Buergi, Sabine; Searcy, Sarah; Sgobbi de Souza, Paulo; Wittenauer, Angela; Fridovich-Keil, Judith

doi:10.1002/jimd.12556

A multinational study of acute and long-term outcomes of Type 1 galactosemia patients who carry the S135L (c.404C > T) variant of GALT

Katler Q. S., Stepien K. M., Paull N., Patel S., Adams M., BALCI M. C., ...Daha Fazla

JOURNAL OF INHERITED METABOLIC DISEASE, cilt.45, sa.6, ss.1106-1117, 2022 (SCI-Expanded, Scopus)

Yayın Türü: Makale / Tam Makale
Cilt numarası: 45 Sayı: 6
Basım Tarihi: 2022
Doi Numarası: 10.1002/jimd.12556
Dergi Adı: JOURNAL OF INHERITED METABOLIC DISEASE
Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, PASCAL, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
Sayfa Sayıları: ss.1106-1117
İstanbul Üniversitesi Adresli: Evet

Özet

Patients with galactosemia who carry the S135L (c.404C > T) variant of galactose-1-P uridylyltransferase (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.