Developmental Outcomes in Duarte Galactosemia

Abstract

OBJECTIVES: For decades, infants with Duarte galactosemia (DG) have been identified by newborn screening (NBS), but whether they should be treated with dietary restrictions of galactose has remained unknown. To clarify, we conducted a study of dietary and developmental outcomes in 206 children with DG (case patients) and 144 controls, all of whom were 6 to 12 years old. METHODS:We recruited case patients from states where they were identified by NBS; unaffected siblings served as controls. Diet in infancy was ascertained by retrospective parent surveys; developmental outcomes were assessed in 5 domains, yielding 73 outcome measures for each child. We divided subjects randomly into independent discovery (n = 87) and validation (n = 263) sets. We tested the discovery set to order the 73 outcome measures by ascending P values and tested the 10 outcomes with the lowest P values for possible association with DG in the validation set. We also tested these same 10 outcomes for possible association with milk exposure in infancy among case patients in the validation set. RESULTS:None of the 73 outcomes tested in the discovery set revealed significant association with DG, and none of the 10 outcomes tested in the validation set revealed either significant association with DG or significant association with milk exposure among children with DG. CONCLUSIONS:Through our results, we demonstrated that there were no significant differences in outcomes tested between case patients and controls or among case patients as a function of milk exposure in infancy. In this study, we provide a long-needed foundation of knowledge for health care providers, families, and NBS professionals seeking to make evidence-based decisions about DG.

<p>Screening for galactosemia: is there a place for it?</p>

“…The dilemma of variants has led to suggestions of lowering the cut-offs for neonatal screening tests. False-positive tests include the detection of glycogen storage disease type XI 81,82…”

Galactosemia: Revisión de la literatura

“…Es la más común, aproximadamente un caso por cada 4000 recién nacidos caucásicos tiene la mutación Duarte-2, donde ocurre una sustitución de asparagina por ácido aspártico (p.N314D). 23,24,25 Si bien los lactantes tienen concentraciones elevadas de metabolitos de galactosa, los pacientes permanecen asintomáticos durante el curso de la vida. 26 Los pacientes homocigotos tienen una actividad enzimática de 50% y los heterocigotos incluso de 75% de actividad normal.…”

“…25 Algunos autores argumentan que ante la elevación de estos metabolitos, ésta es motivo suficiente para llevar a la práctica restricciones transitorias de galactosa; otros sugieren que si el menor se encuentra asintomático no hay motivos para intervención dietética alguna. 24 Por estos argumentos, varios autores han estudiado los efectos de los metabolitos en estos pacientes y, hasta la fecha, no se ha encontrado diferencia significativa en la prevalencia de complicaciones entre quienes tienen galactosemia Duarte y los controles sanos. De igual manera, tampoco hay diferencia en el neurodesarrollo, lenguaje y habla en los pacientes expuestos a dieta de restricción vs los pacientes con variante Duarte alimentados con leche humana o fórmulas lácteas.…”

Heterogeneity of disease‐causing variants in the Swedish galactosemia population: Identification of 16 novel GALT variants

“…Patients with D/G are often detected in NBS programs due to a GALT activity of approximately 25% of normal . Although there is an uncertainty whether these patients need treatment, there are several publications indicating a favorable outcome for D/G patients without treatment with a Gal‐restricted diet …”

“…6 Although there is an uncertainty whether these patients need treatment, there are several publications indicating a favorable outcome for D/G patients without treatment with a Gal-restricted diet. [7][8][9] The first screening method described was a bacterial inhibition assay, 10 followed by the Beutler enzyme spot test. 11 The current methods employed by screening laboratories either measure the activity of the GALT enzyme (EC 2.7.7.12) and/or the amount of total Gal (Gal and Gal-1-P).…”