Introduction
Genetic disorders are a large share of disease and death in childhood. Two big groups are chromosomal disorders (too much, too little or rearranged chromosome material) and inborn errors of metabolism (a single faulty enzyme). Genetic counselling helps families understand the diagnosis and the risk for future children.
Chromosomal disorders
Tests: karyotype (number and large changes), FISH (a known deletion), chromosomal microarray (small gains and losses; first-line for unexplained developmental delay), exome or genome sequencing. Prenatal: combined first-trimester screening, cell-free DNA (NIPT) from 10 weeks, then chorionic villus sampling or amniocentesis to confirm.
Inborn errors of metabolism
Mostly autosomal recessive. A blocked pathway builds up a toxic substrate or lacks a product. Each is rare, together they are common (about 1 in 1000 births).
When to suspect
- A newborn well for the first days who then feeds poorly, vomits, becomes drowsy, has seizures or coma, like sepsis but with negative cultures.
- Unusual smell (maple syrup, sweaty feet), parents related, previous unexplained infant death.
- Hypoglycaemia, metabolic acidosis with high anion gap, high ammonia, high lactate; later, developmental delay, regression, large liver, coarse face.
Emergency treatment of a metabolic crisis
- Stop protein (and lactose if galactosaemia is possible).
- Give IV glucose 10% at high rate to stop catabolism (insulin may be added).
- Correct acidosis; remove toxins: sodium benzoate, phenylbutyrate, carglumic acid for ammonia; dialysis if ammonia is very high; carnitine.
- Take the key samples first: glucose, gas, ammonia, lactate, ketones, plasma amino acids, urine organic acids, acylcarnitines.
Newborn screening by heel-prick blood on day 2–5 finds PKU, congenital hypothyroidism and, in many countries, CF, MCAD deficiency, congenital adrenal hyperplasia and more, before symptoms start.