Pseudo-Zellweger syndrome

What is Pseudo-Zellweger syndrome?

Pseudo-Zellweger syndrome is a rare disease. It is also known as 3-ketoacyl-CoA thiolase deficiency Acyl-CoA oxidase deficiency Bifunctional enzyme (peroxisomal) deficiency Bifunctional enzyme deficiency Peroxisomal beta-keto thiolase deficiency Peroxisomal beta-ketothiolase deficiency Peroxisomal bifunctional enzyme deficiency.

There are a number of patients reported with some of the clinical features of Zellweger syndrome, but with unusual biochemical and morphological abnormalities. Whereas Zellweger patients appear to have a defect involving the formation and maintenance of peroxisomes, leading to a reduced number of peroxisomes in liver and kidney and the reduction in activity of a number of peroxisomal enzymes, pseudo-Zellweger patients have reduced enzyme activities, but with normal appearing peroxisomes.
The key defect is in peroxisomal beta-oxidation of fatty acids, which is catalysed by three enzymes, acyl-CoA oxidase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (bifunctional enzyme) and peroxisomal beta-ketothiolase. Whereas dietary fatty acids are oxidised by the mitochondria the peroxisomes play an important role in the oxidation of very long-chain fatty acids, branched-chain fatty acids (pristanic acid) and bilary intermediates.There are 2 bifunctional proteins - the L and the D forms. Nearly all patients have been found to have a deficiency of the D form (van Grunsven et al., 1999).
Schram et al., (1991) studied case 1 of Goldfischer et al., (1986) and concluded that deficiency of peroxisomal beta-ketothiolase was responsible for the very low peroxisomal beta-oxidation activity and for the accumulation of very long chain fatty acids. However, Ferdinandusse et al., (2002) showed that this patient had a homozygous mutation in the D-bifunctional protein (DBP) gene.
Nakada et al., (1993) reported a case with a possible bifunctional enzyme deficiency, but with detectable enzyme protein. `uki et al., (1994) reported two sibs with similar biochemical findings. These children had hypotonia, hypertelorism, epicanthic folds, low-set ears, and polydactyly. Seizures developed in the first year of life. Clinical features were milder than those of classical Zellweger syndrome, and the eldest child was alive at 7 years. His sister could speak a few words at the age of 4 years and was walking with support at 22 months, although regression followed. Clayton et al., (1988) reported three sibs, born to first cousin parents, with somewhat similar features and normal peroxisomes. There was either a deficiency of peroxisomal thiolase or possibly a bifunctional protein deficiency. Wanders et al., (1990) demonstrated bifunctional protein deficiency in the patient of Clayton et al., (1988).
Pietrzyk et al., (1990) reported a brother and sister who were dificult to classify. They had clinical features overlapping with Zellweger and Pseudo-Zellweger syndrome. The biochemical findings were suggestive of a peroxisomal disorder in sib 1 but not in sib 2.
Schutgens et al., (1994) reported a further case where precise classification was not possible. Development was normal up to 5 months but then progressive retardation with hypotonia, microcephaly, hyporeflexia, deafness and growth retardation became evident. Very long-chain fatty acids were markedly raised in plasma, as were phytanic acid, pipecolic acid, and trihydroxycholestanic acid. However no evidence of biochemical abnormality was found in cultured fibroblasts.
Baumgart et al., (1996) characterised the gene for human peroxisomal branched-chain acyl-CoA oxidase and mapped it to 3p14.3. The enzyme is absent from livers of patients with Zellweger syndrome.
Three Japanese patients were reported by Suzuki et al., (2002). They presented with psychomotor retardation and then regressed. An MRI showed demyelination in white matter in cerebrum and cerebellum and in thepontomedullary corticospinal tracts. Two novel mutations in the acyl CoA oxidase mutations were found.
Corzo et al., (2002) reported three boys with neonatal onset of profound hypotonia, failure to thrive and colestatic liver disease. VLCFA levels were elevated. A deletion involving the ABCD1 gene and the neighbouring gene, DXS1357E was demonstrated. Onset in X-linked adrenoleukodystrophy is not usually until about 7 years of age.

Read More

* This information is courtesy of the L M D.

If you find a mistake or would like to contribute additional information, please email us at: [email protected]

What gene changes cause Pseudo-Zellweger syndrome?

The syndrome is inherited in the following inheritance pattern/s:

Autosomal Recessive - Autosomal recessive inheritance means an affected individual receives one copy of a mutated gene from each of their parents, giving them two copies of a mutated gene. Parents, who carry only one copy of the gene mutation will not generally show any symptoms but have a 25% chance of passing the copies of the gene mutations onto each of their children.

In some cases, a genetic syndrome may be the result of a de-novo mutation and the first case in a family. In this case, this is a new gene mutation that occurs during the reproductive process.

The syndrome can be caused by mutations in the following gene/s location/s:

What are the main symptoms of Pseudo-Zellweger syndrome?

The typical symptoms of the syndrome are:

How does someone get tested for Pseudo-Zellweger syndrome?

The initial testing for Pseudo-Zellweger syndrome can begin with facial genetic analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the type of genetic testing needed. A consultation with a genetic counselor and then a geneticist will follow.

Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.

Get Faster and More Accurate Genetic Diagnosis!

More than 250,000 patients successfully analyzed!
Don't wait years for a diagnosis. Act now and save valuable time.

Start Here!

"Our road to a rare disease diagnosis was a 5-year journey that I can only describe as trying to take a road trip with no map. We didn’t know our starting point. We didn’t know our destination. Now we have hope."


Paula and Bobby
Parents of Lillie

What is FDNA Telehealth?

FDNA Telehealth is a leading digital health company that provides faster access to accurate genetic analysis.

With a hospital technology recommended by leading geneticists, our unique platform connects patients with genetic experts to answer their most pressing questions and clarify any concerns they may have about their symptoms.

Benefits of FDNA Telehealth

FDNA icon


Our platform is currently used by over 70% of geneticists and has been used to diagnose over 250,000 patients worldwide.

FDNA icon


FDNA Telehealth provides facial analysis and screening in minutes, followed by fast access to genetic counselors and geneticists.

FDNA icon

Ease of Use

Our seamless process begins with an initial online diagnosis by a genetic counselor and follows by consultations with geneticists and genetic testing.

FDNA icon

Accuracy & Precision

Advanced artificial intelligence (AI) capabilities and technology with a 90% accuracy rate for a more accurate genetic analysis.

FDNA icon

Value for

Faster access to genetic counselors, geneticists, genetic testing, and a diagnosis. As fast as within 24 hours if required. Save time and money.

FDNA icon

Privacy & Security

We guarantee the utmost protection of all images and patient information. Your data is always safe, secure, and encrypted.

FDNA Telehealth can bring you closer to a diagnosis.
Schedule an online genetic counseling meeting within 72 hours!