6.3 Metabolism Disorders and Inborn Errors

6.3 Metabolism Disorders and Inborn Errors

Quick Answer: A neonate who was well for one to five days and then develops encephalopathy, hypoglycemia, hyperammonemia, metabolic acidosis, or seizures may have an inborn error. Stop feeds, give intravenous glucose to halt catabolism, send ammonia (on ice) plus a blood gas and labs, and call the metabolic team. Do not wait for the newborn screen. Urea-cycle disease is ammonia without much acidosis; organic acidemias add anion-gap acidosis; fatty-acid oxidation disease is hypoketotic hypoglycemia with fasting; galactosemia is milk, liver failure, and E. coli sepsis.

Metabolism disorders on the Neonatal CCRN Test Plan sit next to glucose, calcium, thyroid, and adrenal disease in the Endocrine/Heme/GI/Renal/Integumentary domain. Many of the same infants also appear under Multisystem genetic conditions. This chapter teaches the metabolic emergency. The later genetic-syndromes chapter (Chapter 15) covers trisomies, named malformation syndromes, and the broader genetics conversation. If a crashing neonate needs both a metabolic pathway diagnosis and a syndrome diagnosis, you still start with airway, glucose, ammonia, and NPO.

OpenExamPrep independent study material covers these patient problems as they appear on AACN Certification Corporation's current Neonatal CCRN Test Plan. It does not replace a biochemical genetics service. When the infant is decompensating, speed beats a perfect eponym.

The well interval, then catastrophe

In utero the placenta clears many metabolites and supplies continuous glucose. After birth, milk introduces lactose and protein, fasting happens between feeds, and illness causes catabolism. A classic history is a term infant who fed, looked well, and then on day 2-5 became lethargic, hypotonic, tachypneic, or seizing. That well interval is a clue, not a reassurance. Sepsis remains on the list—you will culture and give antibiotics—but a metabolic disease can look identical and will worsen if you keep giving protein or let the infant fast.

Four laboratory patterns should live in your head:

1. Hypoglycemia that is severe, recurrent, or hypoketotic
2. Hyperammonemia with encephalopathy
3. Metabolic acidosis, especially a high anion gap with ketones or lactate
4. Seizures after a well interval, with or without the labs above

Any one of these in a neonate is enough to stop feeds and involve specialists. Combinations raise the likelihood of an inborn error of metabolism (IEM).

Urea-cycle defects

The urea cycle turns ammonia into urea. When it fails, ammonia rises and injures the brain. Ornithine transcarbamylase (OTC) deficiency is X-linked and often severe in males; females can present too. Infants develop poor feeding, vomiting, tachypnea (ammonia drives ventilation, so a respiratory alkalosis is a clue), lethargy, and coma. Blood gas may show little metabolic acidosis—unlike organic acidemias. Plasma ammonia can be hundreds to thousands of micromoles per liter. Draw ammonia without a tourniquet if possible, put it on ice, and run it immediately; a delayed sitting sample is useless.

Emergency treatment is stop protein, give calories as intravenous glucose (high GIR to stop catabolism), and use nitrogen scavengers and dialysis per the metabolic team. Arginine or citrulline supplementation depends on the exact block. The nursing actions are NPO, glucose, access, ammonia, and the phone call—not starting a high-protein formula because the baby looks hungry.

Organic acidemias

Propionic, methylmalonic, and isovaleric acidemias present when protein (and odd-chain fats in some) cannot be metabolized. After milk protein increases, the infant develops anion-gap metabolic acidosis, ketosis, vomiting, encephalopathy, and often a milder ammonia rise than a pure urea-cycle crisis. Isovaleric acidemia is famous for a sweaty-feet odor. Propionic acidemia may add neutropenia and thrombocytopenia, which can look like sepsis-associated marrow suppression. Treatment again is NPO, glucose, carnitine as directed, correction of acidosis, and metabolic-team recipes—not more formula.

Fatty-acid oxidation disorders

When fasting, the neonate should oxidize fat and make ketones. Fatty-acid oxidation (FAO) defects (MCAD is the most common; VLCAD and LCHAD can involve heart and liver more prominently) block that path. The signature is hypoketotic hypoglycemia with fasting or illness: low glucose, inappropriately low ketones, sometimes hyperammonemia and liver dysfunction, and in severe defects cardiomyopathy or arrhythmias. Historically, MCAD presented as sudden death during a viral illness with poor intake.

The prevention rule is simple and testable: avoid prolonged fasting. Well infants need reliable feed intervals; ill infants need intravenous glucose even if they are not yet numerically hypoglycemic, because the goal is to stop fat breakdown. Do not 'let them sleep through' a 6-8 hour gap. Carnitine is used in selected defects under specialist direction. Section 6.1 already taught GIR; here the point is that glucose is both fuel and a metabolic brake.

Galactosemia

Classic galactosemia (GALT deficiency) means the infant cannot metabolize galactose from lactose in milk. After milk feeds begin, look for jaundice, hepatomegaly, coagulopathy, poor feeding, E. coli sepsis (a classic association), urine reducing substances while on milk, and later cataracts. The immediate action is stop milk—no breast milk, no cow-milk formula—and switch to a soy or elemental galactose-free feeding once the acute crisis allows. Treating sepsis without stopping lactose leaves the toxin on board. Newborn screening catches many cases, but E. coli sepsis can still be the first page.

Reducing substances are a bedside hint, not a standalone diagnosis. You still send the proper enzyme or genetic tests. You do not wait for those results to stop lactose in a jaundiced, coagulopathic neonate on milk with gram-negative sepsis.

Newborn metabolic screen: safety net, not same-day answer

The newborn screen is usually collected at about 24-48 hours of life (timing rules vary by state) and results return in days, not minutes. It is a safety net for infants who are not yet in crisis and for diseases that might otherwise be missed. It is not a reason to delay ammonia, blood gas, glucose, or treatment in a crashing neonate. False negatives happen with early collection, transfusion, total parenteral nutrition, and some milder variants. False positives happen too, especially for 17-OHP in preterm or stressed infants.

If the infant is already encephalopathic, you treat empirically for a metabolic emergency and for sepsis. You still send or repeat the screen as required, but you do not wait for the state lab. Chapter 15 will place many of these enzyme defects next to chromosomal syndromes; the overlapping message is that genetics is not only a dysmorphology exam. A well-then-sick biochemical crash is still a genetics problem even when the infant has no malformation.

Emergency nursing actions

When you suspect a neonatal metabolic emergency:

1. Stop feeds. No protein, no lactose, no 'trial of formula' while you think.
2. Give glucose. Intravenous dextrose at a GIR high enough to stop catabolism (often at least typical neonatal GIR, higher if hypoglycemic). This is the same GIR skill as section 6.1, now used as metabolic therapy.
3. Call the metabolic team (and neonatology/transport if you are not already in a center that can dialyze).
4. Send ammonia on ice, blood gas, lactate, chemistry, glucose, CBC, coagulation if liver failure is in play, and urine for organic acids as directed. Note the time of the last feed.
5. Treat shock, hypoglycemia, hyperkalemia, and sepsis in parallel. Antibiotics do not exclude an IEM.
6. Do not give hypotonic free water as the only therapy for encephalopathy, and do not protein-load a hyperammonemic infant.

The mantra that belongs on a badge card is: stop feeds, give glucose, call metabolic. Everything else—scavengers, carnitine, dialysis, soy formula, specific amino acids—is directed by that team. Your job on the CCRN-style item is to recognize the pattern, not to name every enzyme. Independent practice items for this exam are at /practice/ccrn-neonatal.