La sindrome di Zellweger: un lavoro di squadra

A 1-month female infant with hypotonia, feeding difficulties, facial dysmorphic signs, hepatomegaly and seizures was admitted to the neonatal intensive care unit. Brain magnetic resonance revealed regions of cortical dysplasia, diffuse polymicrogyria (prominent in the frontal and perisylvian cortex), reduction of white matter volume, delayed myelination and germinolytic cysts. The result of the plasma dosage of very long chain fatty acids was very high. Genetic testing revealed a homozygous pathogenetic mutation of the HSD17B4 gene. Thus, clinical features together with biochemical and genetic findings led to the diagnosis of Zellweger spectrum disorder (ZSD). ZSD is included in peroxisome biogenesis disorders. Before the biochemical and molecular bases had been fully determined, ZSD was defined by a continuum of three phenotypes: Zellweger syndrome, neonatal adrenoleukodystrophy and infantile Refsum disease. To identify a continuum of severity of the disease, the terms “severe,” “intermediate” and “milder” ZSD are now preferred. The individuals with ZSD mainly come to clinical attention in the newborn period or in childhood. Occasionally, the subtlety of symptoms delays diagnosis until adulthood. There is not specific therapy, in the severe ZSD prognosis is poor and survival is usually not beyond the first year of life.

Ophthalmic Diagnosis and Novel Management of Infantile Refsum Disease with Combination Docosahexaenoic Acid and Cholic Acid

Infantile Refsum disease is a rare peroxisomal biogenesis disorder characterized by impaired alpha-oxidation and accumulation of phytanic acid in the tissues. Patients often present with fundus changes resembling retinitis pigmentosa, developmental delay, sensorineural hearing loss, ataxia, and hepatomegaly. Traditionally, mainstay treatment for this condition has been a phytanic acid-restricted diet, although supplementation with either docosahexaenoic acid or cholic acid has rarely been described in the literature. We present a case of infantile Refsum disease in a child with retinitis pigmentosa-like ocular findings, sensorineural hearing loss, and self-resolving hepatic disease, who developed novel findings of macular edema refractory to carbonic anhydrase inhibitors. We describe management with a phytanic acid-restricted diet and combination docosahexaenoic acid, and cholic acid therapy, which helped to limit progression of her disease.

Infantile Refsum Disease Associated with Hypobetalipoproteinemia

Infantile Refsum disease (IRD) is a rare peroxisome biogenesis disorder with wide range of clinical severity. Herein, we report a mild form of IRD who had been followed as a symptomatic hypobetalipoproteinemia resembling with abetalipoproteinemia. At 6 years of age, the patient was diagnosed as having hypobetalipoproteinemia with spinocerebellar degeneration, peripheral neuropathy, retinitis pigmentosa, mild mental retardation, and sensorineural hearing loss. Although low vitamin E levels normalized after oral supplementation, the patient's clinical symptoms worsened very slowly. At 30 years of age, elevated levels of very long chain fatty acids and phytanic acid and decreased plasmalogen levels were detected in the plasma. Genetic analysis revealed a homozygous mutation of Q67R in PEX10.Although hypocholesterolemia is relatively common in IRD, it has been overlooked so far. Since there are many similarities between IRD and abetalipoproteinemia or symptomatic hypobetalipoproteinemia, care should be taken to differentiate symptomatic hypobetalipoproteinemia from IRD.