Holoprosencephaly (HPE) is a condition characterized by a defect in the development of the midline embryonic forebrain. When detected prenatally, the diagnosis of HPE offers parents a poor but often uncertain prognosis. Since the majority of parents receiving a prenatal diagnosis of an abnormality terminate their pregnancies, few studies have examined parents' experiences and needs surrounding the decision to continue a pregnancy. We present a descriptive study of in-depth interviews with 24 parents who chose to continue their pregnancy after receiving a prenatal diagnosis of HPE. Parents were asked about their decision-making process to continue the pregnancy. Qualitative analysis was used to identify common themes that emerged from these parents' experiences. The results suggest that most parents did not make an active decision about continuing the pregnancy. Rather, they described a more subtle decision-making process that evolved over time and consisted of several factors. These factors included the parents' religious and personal beliefs, past experiences, and the uncertainty involved in the diagnosis of HPE. Throughout the decision-making process, they described informational, emotional, and supportive needs from family, friends, and health professionals. All of these factors contributed to the evolution of the parents' decision to continue the pregnancy and the acceptance of their decision. Results of this exploratory study suggest health care professionals need to work with parents as they make their decision to continue an affected pregnancy. The results also provide the groundwork for prospective investigation into parents' decision-making process as they receive and adjust to prenatal diagnoses of an abnormality.

Screened for by all state newborn screening (NBS) programs in the United States, mitochondrial acetoacetyl-coenzyme A thiolase (T2), or β-ketothiolase, deficiency is a rare autosomal recessive disorder that causes ketoacidosis and hypoglycemia/hyperglycemia. Outcomes vary from normal development to severe cognitive impairment or even death after an acute episode of ketoacidosis. The classical biochemical profile of T2 deficiency is a result of null mutations in both alleles of the ACAT1 gene and consists of persistently increased urinary excretion of ketones, characteristic organic acids, and tiglylglycine as well as abnormal blood or plasma acylcarnitine profiles in acute and stable conditions. Early diagnosis and aggressive management can prevent further episodes of ketoacidosis and lead to normal development. We report the cases of 3 children, all subsequently found to have mutations predicted to be associated with no residual T2 enzymatic activity, but only 1 was identified by NBS in Minnesota since 2001. To our knowledge, this is the first description of compound heterozygotes for null mutations associated with no enzymatic activity exhibiting normal urinary organic acid, blood, and plasma acylcarnitine profiles when clinically well, thereby explaining the false-negative NBS results. We suggest that T2 deficiency may be underrecognized, because the incidence of T2 deficiency in Minnesota, on the basis of these 3 cases, is 1 in 232 000, higher than the reported <1 in 1 million incidence. Our cases emphasize that T2 deficiency must be considered in patients who present with ketoacidosis disproportionately severe to the triggering illness despite normal NBS results or nonspecific biochemical findings in blood and urine during asymptomatic periods.