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Inheritance
•    Autosomal recessive inheritance pattern.
•    All affected individuals are homozygous for predicted loss-of-function variants.
•    Most families are consanguineous, though cases have been reported in non-consanguineous families.

Prevalence
•    Rare disorder, with 14 affected individuals identified across 9 unrelated families from diverse geographic backgrounds (Turkey, Saudi Arabia, Iran, Morocco, Ethiopia, Eritrea).
•    Likely underdiagnosed, especially in populations with high consanguinity.

Genetic Etiology
•    Caused by biallelic loss-of-function mutations in WDR83OS(NM_016145.4).
•    Mutation types include:
- Nonsense variants (e.g., p.Gln79*, p.Glu24*)
- Canonical splice site variants (e.g., c.156+1G>T, c.156+2T>A, c.50+1G>T)
- Small deletions affecting splice acceptor and coding regions

Pathophysiology
•    WDR83OSencodes Asterix, a 106-aa protein that forms the PAT complex with CCDC47.
•    The PAT complex functions as an ER-associated chaperone for transmembrane proteins.
•    Loss of Asterix disrupts protein folding, potentially leading to: a) ER stress, b) defective bile acid transport or tight junction integrity, c) impaired lipid absorption d) neurodevelopmental dysfunction

Main Clinical Features
Neurological
•    Global developmental delay
•    Intellectual disability (moderate to severe)
•    Hypotonia
•    Autistic features
•    Seizures (e.g., myoclonic)
•    Poor expressive language

Facial Dysmorphism: There is no recognizable facial gestalt, however common features include prominent philtrum, everted lower lip, tented/open mouth, ptosis, hypo- or hypertelorism, synophrys or thick eyebrows, micrognathia or prognathism, depressed nasal bridge and strabismus.

Hepatic and Gastrointestinal
•    Hypercholanemia (elevated serum bile acids)
•    Intractable pruritus
•    Hepatomegaly
•    Gallstones
•    Steatorrhea, chronic diarrhea
•    Feeding difficulties
•    Fat malabsorption

Growth
•    Failure to thrive
•    Progressive microcephaly in some cases

Other Findings
•    Congenital anomalies (skeletal, renal, cardiac)
•    Endocrine abnormalities (e.g., premature thelarche)

Diagnostic Workup
•    Genetic testing: Exome sequencing (trio or proband), Sanger confirmation
•    Biochemical: Serum bile acids, liver enzymes (ALT, AST, ALP), bilirubin, GGT
•    Imaging: Brain MRI, liver ultrasound
•    EEG: For seizure evaluation