Zellweger syndrome with severe malnutrition, immunocompromised state and opportunistic infections

Abstract

Peroxisome biogenesis disorders are related to a spectrum of genetic diseases that range from severe Zellweger syndrome to milder infantile Refsum disease. Zellweger syndrome is characterised by dysmorphic features, severe hypotonia, seizures, failure to thrive, liver dysfunction and skeletal defects. Increased levels of very long chain fatty acids are the biochemical hallmark and the most common mutations found in the PEX1 gene. We report an unusual presentation of Zellweger syndrome in a 2-month-old female infant with severe malnutrition, opportunistic infections, lymphopaenia and a small thymic shadow on chest radiography. With this clinical picture, an initial hypothesis of primary immunodeficiency was considered. It was later confirmed to not be the case. On follow-up, global developmental delay, bilateral optic nerve atrophy and moderate bilateral sensorineural deafness grade II were documented. There were no further infectious complications and we concluded malnutrition was the cause of the infant's immunocompromised state.

Characterization of Severity in Zellweger Spectrum Disorder by Clinical Findings: A Scoping Review, Meta-Analysis and Medical Chart Review

“…There were 10 cohort studies [ 12 , 28 , 29 , 39 , 51 , 58 , 98 , 99 , 100 , 101 ] and 18 case studies [ 60 , 93 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 ] that described 77 (54 from cohort studies, 23 from case studies) patients with an intermediate form of ZSD. In the cohort studies, the prevalence of seizures (51.0%, out of n = 51), brain abnormalities (15.4%, out of n = 26), hypotonia (97.6%, out of n = 41), reduced mobility (70.8%, out of n = 24), feeding difficulties (52.9%, out of n = 17), abnormal liver function or structure (79.0%, out of n = 38), adrenal insufficiency (57.1%, out of n = 28), and hearing loss (57.1%, out of n = 28) was significantly greater in the intermediate category compared to the mild category ( p ≤ 0.011, Table 1 ).…”

The peroxisomal disorder spectrum and Heimler syndrome: Deep phenotyping and review of the literature

“…The patient had developmental delay, facial dysmorphism and biochemical abnormalities. Also, the missense c.2528G>A was found in trans with c.760dupT in a patient with ZS (Cardoso, Amaral, Lemos, & Garcia, 2016). Regarding PEX6 , c.1802G>A was described in a patient with development regression, biochemical abnormalities and brain leukodystrophy.…”

Case Report: Zellweger Syndrome and Humoral Immunodeficiency: The Relevance of Newborn Screening for Primary Immunodeficiency

“…The first report was written in 1974 by Gilchrist et al (20), who described, in a letter published on Lancet, a defect in the differentiation and function of T cells in clinical cases of ZS. Afterward, in 2016, Cardoso et al (21) described the case of a patient affected by ZS who drastically improved his state of profound T-lymphopenia after obtaining a full recovery of his nutritional status. Nevertheless, the association between peroxisomes and humoral defects has never been described so far.…”