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In the neonate, the early clinical features of acute metabolic decompensation are almost always non-
specific; they include “unwell”, lethargy, feeding problems, vomiting, abnormal breathing, hypotonia
and seizures.
Asymptomatic interval with clinical manifestations from the second day of life onwards (“intoxication
type”) are typical in newborns.
The baby’s general condition will usually deteriorate rapidly despite normal or non-specific findings in
routine investigations (laboratory signs of infection, lumbar puncture, chest X-ray, cranial ultrasound)
and antibiotic therapy.
Metabolic disorders after the neonatal period may present with recurrent vomiting and lethargy
progressing to coma without focal neurological signs or typical patterns of organ dysfunction.
A metabolic disorder should be considered, along with other diagnoses (e.g. infection, CNS
pathology) …
… in all neonates with unexplained, overwhelming or progressive disease particularly after normal
pregnancy and birth
… in all children with acute deterioration of the general condition and/or reduced consciousness,
particularly when preceded by vomiting, fever or fasting
… in all children with symptoms and signs of acidosis or hypoglycemia
Appropriate diagnostic and therapeutic measures must be initiated as soon as possible to avoid long-
term damage
Hyperammonemia:
NH3 values
Neonates: healthy < 110 umol/l, sick up to 180 umol/l, suspect metabolic disease >200 umol/l
It is essential to measure ammonia early in every sick child in whom a metabolic disease may be the
underlying diagnosis. Hyperammonemia may be missed otherwise and the child may be deprived of
efficient treatment.
Causes:
- Urea cycle disorders: most common cause of severe hyperammonemia presenting with
progressive or chronic relapsing encephalopathy. May initially be associated with respiratory
alkalosis but acidosis can occur. Short time-span from first symptoms to irreversible brain
damage – rapid and efficient management is of utmost importance!
- Organic acidurias (e.g. propionic aciduria)- approx. 30% of severe neonatal
hyperammonemias: Blocked urea synthesis due to its inhibition by organic acids and due to
deficiency of acetyl-CoA (required in urea cycle). Usually associated with (lactic) acidosis at an
early stage.
- Severe liver failure (secondary hyperammonemia!!!)
- Transient hyperammonemia of a newborn due to open ductus venosus
Emergency management:
Disorders with characteristic accumulation of carboxylic acids identified by GC/MS analysis of urine.
The most important acidurias are caused by disorders involving the complex metabolism of branched-
chain amino acids. The most common acidurias: propionic aciduria, methylmalonic aciduria, isovaleric
aciduria.
Clinical:
Lab:
Diagnosis:
- Organic acids (specific metabolites) in urine (GC/MS analysis), amino acids in plasma
Therapy:
- Acute: Interrupt catabolic state with high-dose glucose infusion, counteract acidosis, stop
protein intake, remove toxins, give carnitine
Complications:
Phenylketonuria (PKU)
PKU was one of the first neurogenetic disorders identified, the first successfully treated inborn error
of metabolism (diet) and the disorder that was instrumental for the introduction of neonatal
population screening (dried blood spots). A deficiency of the enzyme phenylalanine hydroxylase
(PAH) causes the accumulation of phenylalanine leading to severe brain damage with mental
retardation if untreated. Average incidence 1:8000.
Diagnosis:
- Neonatal screening (filter paper card), amino acids in plasma: Phe, n- Tyr
Therapy:
Prognosis:
- Fetopathy in pregnant mothers with PKU (brain underdevelopment, congenital heart defects
in the fetus)
- Strict diet treatment must be started before conception and maintained throughout
pregnancy!!!
Galactosemia
Patients develop clinical symptoms only after intake of lactose (milk, milk products) in the diet.
Galactose-1-phosphate which accumulates in classical galactosemia is toxic for the liver, kidneys and
brain.
Clinical:
- Progressive symptoms after start of milk feeds, usually starting on the 3 rd or 4th day of life
- Vomiting, diarrhea, jaundice, disturbances of liver function, sepsis death from hepatic and
renal failure
- Bilateral cataract
Diagnosis:
Therapy:
Prognosis:
Reference: