Long-term Outcomes of Individuals With Metabolic Diseases Identified Through Newborn Screening

Abstract

BACKGROUND: Although extended newborn screening (NBS) programs have been introduced more than 20 years ago, their impact on the long-term clinical outcome of individuals with inherited metabolic diseases (IMDs) is still rarely investigated. METHODS: We studied the clinical outcomes of individuals with IMDs identified by NBS between 1999 and 2016 in a prospective multicenter observational study. RESULTS: In total, 306 screened individuals with IMDs (115 with phenylketonuria and 191 with other IMDs with a lifelong risk for metabolic decompensation) were followed for a median time of 6.2 years. Although the risk for metabolic decompensation was disease-specific and NBS could not prevent decompensations in every individual at risk (n = 49), the majority did not develop permanent disease-specific signs (75.9%), showed normal development (95.6%) and normal cognitive outcome (87.7%; mean IQ: 100.4), and mostly attended regular kindergarten (95.2%) and primary school (95.2%). This demonstrates that not only individuals with phenylketonuria, serving as a benchmark, but also those with lifelong risk for metabolic decompensation had a favorable long-term outcome. High NBS process quality is the prerequisite of this favorable outcome. This is supported by 28 individuals presenting with first symptoms at a median age of 3.5 days before NBS results were available, by the absence of neonatal decompensations after the report of NBS results, and by the challenge of keeping relevant process parameters at a constantly high level. CONCLUSIONS: NBS for IMDs, although not completely preventing clinical presentations in all individuals, can be considered a highly successful program of secondary prevention.

Newborn screening and disease variants predict neurological outcome in isovaleric aciduria

“…This emphasizes the need to optimize the diagnostic NBS process to that NBS results are available early, preferably before or by day 5, to prevent life-threatening and prognostically relevant severe neonatal decompensations. 3,16 Despite positive NBS result, the subsequently implemented therapeutic strategies for classical IVA neither were sufficient to prevent metabolic decompensations in 25% patients after the diagnosis was known nor the manifestation of recurrent episodes in 41% of decompensated individuals with classic IVA. Here, evaluation of impact of therapy on outcome in classic IVA in larger international cohorts and deducted guidelines for therapy of classic IVA are urgently needed, especially for the vulnerable period in infancy and childhood.…”

“…The national multicenter observational study included individuals with IVA identified by NBS between 1 January 1998 and 31 December 2018, significantly extending the prospective multicenter observational NBS study in Southwest Germany (DRKS-ID: DRKS00013329 16 ). Inclusion criteria were (a) positive NBS result, (b) confirmation of IVA according to the national NBS guideline, 22 and (c) written informed consent of patients and/or caregivers.…”

“…None of the individuals with mild IVA (N = 67) experienced a metabolic decompensation during the study period, while 17 of 24 (71%) individuals of the classic IVA group had at least one metabolic decompensation, 13 of these (54%) already during the newborn period (EO group, Figure 1) and 11 (46%) before the NBS result was known. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] days; P = .0018; Table 2), with highest frequencies (mean [SD]) during the first year of life (classic 1.7 [1.6]; mild 0.5 [1.1]). The major cause of hospitalization in classic IVA was prevention of (impending) metabolic decompensation (83.5%).…”

Real‐world management of maple syrup urine disease (MSUD) metabolic decompensations with branched chain amino acid‐free formulas in France and Germany: A retrospective observational study

“…If diagnosed and treated early, prognosis is generally good 12,13 . MSUD is managed by a protein‐restricted diet with BCAA‐free formula supplementation 2,4 .…”

“…When oral or enteral administration is difficult or impossible (ie, in cases of vomiting, coma or seizures), or in case of refusal of nasogastric tube feeding, an intravenous (IV) formula may be necessary 15‐17 . Although not widely available in Europe, IV BCAA‐free formula has been used in France since 2010 for the treatment of metabolic decompensation episodes in emergency settings or in combination with or as an alternative to invasive extracorporeal procedures, such as hemodialysis and/or hemofiltration (HD/HF) 12‐14 …”