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Zellweger Syndrome (Classic Cerebro-Hepato-Renal Type)
Most Identifiable Symptom: Profound hypotonia and no developmental progress with distinctive dysmorphic facial features (high forehead, flat facies, large anterior fontanel).
Genetic Inheritance & Gene: Autosomal Recessive. Multiple PEX genes (e.g., PEX1).
Key Biochemical Finding: ↑ VLCFAs, ↑ Phytanic/Pristanic acid, ↑ Pipecolic acid, ↓ Plasmalogens.
Treatment: Supportive only; consider hospice. Death in first year.
Neonatal Adrenoleukodystrophy (NALD)
Most Identifiable Symptom: Hypotonia, severe global developmental delay/regression, and transient "leopard spot" retinopathy.
Genetic Inheritance & Gene: Autosomal Recessive. Multiple PEX genes.
Key Biochemical Finding: ↑ VLCFAs, ↑ Phytanic/Pristanic acid, ↑ Pipecolic acid, ↓ Plasmalogens.
Treatment: Supportive only. Death in infancy or early childhood.
Infantile Refsum Disease
Most Identifiable Symptom: Onset in infancy/childhood with developmental delay, retinitis pigmentosa, and sensorineural hearing loss. Some may have normal intellect.
Genetic Inheritance & Gene: Autosomal Recessive. Multiple PEX genes.
Key Biochemical Finding: ↑ VLCFAs, ↑ Phytanic/Pristanic acid, ↑ Pipecolic acid, ↓ Plasmalogens.
Treatment: Supportive only.
X-linked Adrenoleukodystrophy (X-ALD) - Cerebral Childhood Form (cALD)
Most Identifiable Symptom: Progressive inflammatory demyelination with learning/behavioral deficits, seizures, and dementia. Average onset 4-8 y/o. MRI is abnormal before symptoms.
Genetic Inheritance & Gene: X-linked. ABCD1 gene.
Key Biochemical Finding: ↑ C22, C24, C26 VLCFAs. C26:0-lysoPC on NBS.
Treatment: Therapies listed include Leriglitazone, In-vivo AAV9 gene therapy, and ex-vivo gene therapy (Skysona).
X-linked Adrenoleukodystrophy (X-ALD) - Adrenomyeloneuropathy (AMN)
Most Identifiable Symptom: Spastic paraplegia, loss of bladder/bowel control, sexual dysfunction. Symptoms progress over decades. Onset in adulthood.
Genetic Inheritance & Gene: X-linked. ABCD1 gene.
Key Biochemical Finding: ↑ C22, C24, C26 VLCFAs.
Treatment: Therapies listed include Leriglitazone, oral thyroid agonist, and Pioglitazone.
X-linked Adrenoleukodystrophy (X-ALD) - Addison Disease Form
Most Identifiable Symptom: Adrenal dysfunction only in childhood (~7 y/o), presenting with fatigue, vomiting, dehydration, and risk of metabolic crisis.
Genetic Inheritance & Gene: X-linked. ABCD1 gene.
Key Biochemical Finding: ↑ C22, C24, C26 VLCFAs.
Treatment: (Not specified separately; management is standard).
Rhizomelic Chondrodysplasia Punctata (RCDP)
Most Identifiable Symptom: Disproportionate short stature (rhizomelia) and punctate calcifications in cartilage.
Genetic Inheritance & Gene: Autosomal Recessive. Type 1: PEX7 (biogenesis), Type 2: GNPAT, Type 3: AGPS.
Key Biochemical Finding: Normal VLCFAs, ↓ Plasmalogens, ↑ Phytanic acid.
Treatment: Dietary restriction of phytanic acid. Reduced life expectancy.