Paediatrics: Inherited renal disease

2021-03-04 12:00 AM

Many renal abnormalities are inherited. Recognition of these is important, not only in terms of diagnosis and treatment of the patient but also for screening and genetic counselling for the whole family.

Inherited renal disease

Many renal abnormalities are inherited. Recognition of these is important, not only in terms of diagnosis and treatment of the patient, but also for screening and genetic counselling for the whole family.

  • New therapies may become available as gene therapy is researched.
  • Ethical considerations are very important in this group in terms of family screening and counselling.
  • Databases such as Online Mendelian Inheritance in Man (OMIN) provide comprehensive lists. Below are a few of the more common conditions.

Autosomal dominant inheritance

Polycystic kidney disease (ADPKD). Commonest inherited renal disease (1/400 to 1/1000), which usually only manifests in adult life, but cysts can be seen on US scan in children. Multi-organ involvement (intracranial aneurysms, liver and pancreatic cysts, mitral valve prolapse), abdominal mass, haematuria, pain (rare presentation in neonatal period with abdominal masses and/or high or low BP, renal impairment).

Tuberous sclerosis

  • Skin: ‘ash-leaf’ macule; adenoma sebaceum; shagreen patch.
  • Neurological: seizures.
  • Cardiac: rhabdomyoma.
  • Renal: cysts; angiomyolipomas; high or low BP; renal impairment.
  • Neurofibromatosis: neurofibroma, renal artery stenosis; therefore, BPshould be monitored.
  • Branchio-oto-renal syndrome Hearing loss, branchial arch defects, renal anomalies.

Autosomal recessive inheritance

Polycystic kidney disease (ARPKD)

  • Incidence 1:20 000 to 1:40,000.
  • Oligohydramnios and large echogenic kidneys.
  • Fusiform dilatation of collecting tubules.
  • Prognosis depends on degree of pulmonary involvement.
  • This usually presents at an earlier age than ADPKD and progresses to renal failure in a shorter time.
  • Liver involvement leads to portal hypertension in later life
  • Bardet–Biedl syndrome: obesity, polydactyly, mental retardation,retinitis pigmentosa, hypogenitalism, renal anomalies commonly found.
  • Cystinosis (Fanconi’s syndrome): excess storage of cystine due to defectin transport system of cystine out of cell. Accumulates in various organs (cornea, thyroid, brain, leading to growth failure)—eventual renal failure.
  • Nephronophthisis: polyuria, polydipsia, tubulopathy and childhood onsetrenal failure.
  • Primary hyperoxaluria: (renal calculi).
  • Cystinuria: recurrent calculi.

X-linked

  • Alport’s syndrome: sensorineural deafness with progressive nephritis.
  • Nephrogenic diabetes insipidus.
  • Fabry’s disease: deficiency of alpha-galactosidase A; now treatable.

Sporadic

  • VATER association: vertebral, anal, tracheo-oesophageal, radial/renal; renal problems include agenesis, ectopy, or obstruction.
  • CHARGE association: Coloboma, heart defects, choanal atresia, retarded growth, genital anomalies, ear abnormalities (renal anomalies include dysplasia, agenesis, and ectopy).
  • Turner’s (XO): horseshoe or duplex kidneys.
  • William’s syndrome: hypertensive, hypercalcaemia.
  • Bartter’s: metabolic alkalosis, low K+, high aldosterone with normal BP.