Most inborn errors of metabolism are inherited by an autosomal recessive mode of inheritance. Which of the following is an example of an inborn error of metabolism with X-linked recessive inheritance and significant variability in clinical phenotype?
A. Ornithine transcarbamylase deficiency
C. Methylmalonic acidemia
D. Biotinidase deficiency
Most inborn errors of metabolism (IEMs) are inherited as autosomal recessive conditions. A significant minority are inherited as X-linked recessive disorders and a few as dominant disorders. However, in developed countries, where consanguinity is rare and the size of sibships small, many cases appear to be sporadic with a negative family history. It is important to remember that ornithine transcarbamylase deficiency, the most common urea cycle defect, is an X-linked disorder with a very variable phenotype in females that can lead to fatal hyperammonemia in both affected males and females. The other disorders listed are inherited in an autosomal recessive form.
A 3-day-old male neonate presents to the emergency department (ED) with a 1-day history of poor feeding. He was born to a 21-year-old primigravida after a normal pregnancy and delivery. In the ED, you note that he is lethargic. Vitals are notable for temperature of 36.7°C, heart rate of 185 bpm, respiratory rate of 46 breaths/min, and blood pressure of 65/35 mm Hg. During your evaluation, the patient becomes increasingly hypotonic and does not respond to sternal rub. Arterial blood gas reveals a respiratory alkalosis, normal glucose, and normal lactic acid level. Of the following, which is the most important next diagnostic test?
C. Urine-reducing substances
E. Plasma acylcarnitine profile
The neonate has a limited repertoire of responses to severe illness, and inborn errors of metabolism (IEMs) may present with nonspecific symptoms (Table 129-1). Consider IEMs in parallel with other more common conditions such as sepsis. Rapid clinical deterioration is concerning for IEMs.
Isolated hyperammonemia can occur without acidosis or an elevated lactate. An elevated ammonia level alone can induce respiratory alkalosis. Respiratory alkalosis is ...