U01.01.056 Autosomal recessive diseases

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Learning Objectives

  • Identify the classic Autosomal Recessive (AR) disorders and their associated enzyme defects.
  • Distinguish between ARPKD and its dominant counterpart.
  • Master the clinical presentations of Cystic Fibrosis, Wilson’s disease, and PKU.

1. Core Autosomal Recessive Disorders

Unlike dominant disorders (often structural), recessive diseases usually involve enzyme deficiencies.

Category Examples
Metabolic PKU, Galactosemia, Alkaptonuria, Albinism.
Storage Sphingolipidoses (except Fabry), Glycogen Storage Diseases (GSDs), Mucopolysaccharidoses (except Hunter).
Hematologic Sickle Cell Disease, Thalassemia, Hemochromatosis.
Other Cystic Fibrosis, Friedreich Ataxia, Kartagener Syndrome, Wilson’s Disease.

2. Focus: Autosomal Recessive Polycystic Kidney Disease (ARPKD)

Since you asked for the high-scoring features of ARPKD, here is the clinical breakdown often tested on the boards:

  • Genetics: Mutation in the PKHD1 gene (fibrocystin).
  • Age of Onset: Typically presents in infancy or childhood (neonatal period).
  • Kidney Findings: Bilateral enlargement with thousands of small, radially oriented cysts in the collecting ducts.
  • Associated Extra-renal Findings:
    • Congenital Hepatic Fibrosis: Leads to portal hypertension and esophageal varices.
    • Potter Sequence: Oligohydramnios in utero leading to pulmonary hypoplasia, flattened facies, and limb deformities.

3. High-Yield Exceptions (The “Rules of 2”)

Always remember the outliers that are X-linked rather than Autosomal Recessive:

  • Sphingolipidoses: All are AR except Fabry disease.
  • Mucopolysaccharidoses: All are AR except Hunter syndrome (“The hunter needs to see the target, so he doesn’t have corneal clouding”).

 

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