Discrepant molecular and clinical diagnoses in Beckwith-Wiedemann and Silver-Russell syndromes.

Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS) are two imprinting disorders associated with opposite molecular alterations in the 11p15.5 imprinting centres. Their clinical diagnosis is confirmed by molecular testing in 50-70% of patients. The authors from different reference centres for BWS and SRS have identified single patients with unexpected and even contradictory molecular findings in respect to the clinical diagnosis. These patients clinically do not fit the characteristic phenotypes of SRS or BWS, but illustrate their clinical heterogeneity. Thus, comprehensive molecular testing is essential for accurate diagnosis and appropriate management, to avoid premature clinical diagnosis and anxiety for the families.

Autism: Screening of inborn errors of metabolism and unexpected results.

In this study, the aim was to examine patients with inborn errors of metabolism (IEM) who presented with only autism, without any other findings, to suggest any other neurological and genetic disorders. To investigate IEM, data of the hospital records of 247 patients who were referred from pediatric psychiatric to pediatric metabolism outpatient clinics due to further evaluation of autism spectrum disorders (ASD) were examined. Among them, 237 patients were evaluated for IEM leading to ASDs. Organic acidemias, phenylketonuria, tetrahydrobiopterin and neutrotransmitter disorders, biotinidase deficiency, Smith-Lemni-Opitz syndrome, disorders of cerebral creatine metabolism, urea cycle defects, homocystinuria, purine-pyrimidine metabolism disorders, mitochondrial disorders, cerebrotendinous xantomatosis, mucopolysaccaridosis, and glucose 6 phosphate dehydrogenase deficiency were screened with complete blood counts, complete biochemical analyses, homocysteine levels, an arterial blood gase, and metabolic investigations. Six patients were diagnosed as follows: one with phenylketonuria (PKU), one with cerebral creatine deficiency, one with hypobetalipoproteinemia, one with glycogen storage disease type IX-a, one with dihydropyrimidine dehydrogenase deficiency, and one with succinic semialdehyde dehydrogenase deficiency (SSADHD). Forty-six patients screened for IEM were from consanguineous families, among them, one was diagnosed with FKU and the other was with SSADHD. It would not be expected to find PKU in a 5-year-old patient as a result of newborn screening, but she could not been screened due to being a refugee. The diagnosed diseases were rare presentations of the diseases and furthermore, the diagnosis of hypobetalipoproteinemia and glycogen storage disease type IX-a were surprising with the only presentation of ASDs. LAY SUMMARY: It is well-known that some types of inborn errors of metabolism (IEM) may present with that of autism spectrum disorders (ASDs). This study suggests that in countries where consanguinity marriages are common such as Turkey and refugees whose escaped from neonatal screening are present, patients with ASD should be screened for IEMs. The results can surprise the physicians with a very rare cause of autism that has never been thought. Autism Res 2021, 14: 887-896. © 2021 International Society for Autism Research, Wiley Periodicals LLC.